Bronchiectasis

Respiratory Disease MONDO:0004822 Pathograph 22 Show in embeddings browser Chronic Lung Disease Inflammatory Lung Disease

Bronchiectasis is a chronic respiratory disease characterized by permanent, abnormal dilation and thickening of the bronchi resulting from a self-perpetuating cycle of airway infection, inflammation, impaired mucociliary clearance, and progressive structural lung damage (the so-called vicious vortex). It may be idiopathic or arise secondary to prior severe respiratory infection, cystic fibrosis, primary ciliary dyskinesia, immunodeficiency, allergic bronchopulmonary aspergillosis, or chronic obstructive airway disease. Affected individuals experience chronic productive cough, recurrent respiratory infections, and progressive airflow obstruction, with acute exacerbations driving stepwise decline in lung function.

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Classifications

Harrison's Part
RESPIRATORY
🔗

Mappings

MONDO
MONDO:0013087 bronchiectasis with or without elevated sweat chloride 2 Not Yet Curated
skos:narrowMatch dismech
The ENaC-subunit branch of this disease. MONDO:0013087 (BESC2) and MONDO:0013112 (BESC3) are grandchildren of this entry's MONDO:0004822 anchor, through MONDO:0018956 idiopathic bronchiectasis, and their OWL axioms assert SCNN1A (hgnc:10599) and SCNN1G (hgnc:10602) respectively as causal genes. Both genes are curated on this entry as `genetic:` records wired to the Airway Surface Liquid Dehydration node. They are typed `SUSCEPTIBILITY` rather than `CAUSATIVE`, and no gene-defined `has_subtypes` row is created, because the primary reports describe heterozygous variants and case-control enrichment rather than Mendelian segregation of a clinically separable entity. The report behind MONDO:0013112 found five beta- and gamma-subunit amino-acid changes, two of them in SCNN1G, in the heterozygous state in 8 of its 55 patients, and concluded that they "might be deleterious", with the effect clearest in trans-heterozygotes who also carry a CFTR variant. The report behind MONDO:0013087 attributes only "a small fraction" of its cohort to a Mendelian mechanism and otherwise reports a more than three-fold excess of rare ENaC polymorphisms over controls. This is a considered disagreement with MONDO's `RO:0004003` typing, not an omission.
MONDO:0013112 bronchiectasis with or without elevated sweat chloride 3 Not Yet Curated
skos:narrowMatch dismech
The SCNN1G half of the same ENaC branch; see the justification on MONDO:0013087 above, which covers both terms.
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Pathophysiology

9
Chronic Infection and Inflammation
Persistent microbial infections and inflammation damage airway walls, leading to dilation and thickening.
Downstream
Neutrophil-Driven Inflammation Persistent airway infection and higher bacterial burden sustain the characteristic neutrophilic inflammatory response.
Airway Dilation Persistent infection, inflammation, and mucus obstruction cause progressive structural airway damage that culminates in irreversible bronchial dilation.
Pulmonary Exacerbations Recurrent increases in infection and inflammation manifest clinically as pulmonary exacerbations.
Fatigue The chronic disease burden and exacerbation episodes contribute to clinically important fatigue.
Show evidence (1 reference)
DOI:10.1183/16000617.0055-2024 SUPPORT Human clinical
"The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology."
Vicious vortex model centers on chronic infection plus inflammation as the core pathophysiology of bronchiectasis.
Airway Dilation
Destruction of elastin and cartilage in the bronchial walls causes irreversible dilation of bronchi.
Downstream
Impaired Mucociliary Clearance
Fixed Airflow Obstruction Irreversible structural destruction and dilation of the bronchial walls produces the progressive, fixed airflow limitation seen in bronchiectasis.
Dyspnea Airway structural damage and airflow limitation manifest clinically as breathlessness.
Wheezing Distorted, dilated airways and luminal narrowing during airflow produce wheeze.
Hemoptysis Bronchial wall destruction with hypertrophied, fragile bronchial arteries predisposes to airway bleeding.
Crackles Distorted, secretion-filled airways generate discontinuous adventitious sounds on auscultation.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"AbstractBronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome."
The review identifies permanent bronchial dilation as the defining structural abnormality.
Airway Surface Liquid Dehydration
An epithelial ion-transport route into the vicious vortex, separate from the infection-driven route. Hyperactive epithelial sodium channel (ENaC) function increases sodium absorption across the airway epithelium and draws water out of the airway surface liquid; reduced CFTR-mediated chloride and fluid secretion acts in the same direction. The resulting dehydrated, viscous surface liquid impairs mucus transport, which is why variants in the ENaC subunit genes are found in idiopathic bronchiectasis and why the effect is clearest in patients who also carry a CFTR variant.
airway epithelial cell CL:0002368 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves airway epithelial cell, annotated with respiratory tract epithelial cell (CL:0002368). CL:0002368 is a cell type from the Cell Ontology.
SCNN1A hgnc:10599 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SCNN1A (hgnc:10599). hgnc:10599 is a gene from the HUGO Gene Nomenclature Committee. SCNN1G hgnc:10602 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SCNN1G (hgnc:10602). hgnc:10602 is a gene from the HUGO Gene Nomenclature Committee. CFTR hgnc:1884 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CFTR (hgnc:1884). hgnc:1884 is a gene from the HUGO Gene Nomenclature Committee.
amiloride-sensitive sodium channel (ENaC) activity GO:0015280 ⇑ GAIN OF FUNCTION Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves amiloride-sensitive sodium channel (ENaC) activity, annotated with ligand-gated sodium channel activity (GO:0015280), qualified as gain of function. GO:0015280 is a molecular function from the Gene Ontology.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Impaired Mucociliary Clearance A dehydrated, hyperconcentrated periciliary layer prevents effective ciliary mucus transport, feeding the same clearance failure that airway dilation produces by a structural route.
Show evidence (2 references)
PMID:18507830 SUPPORT Human clinical
"Our results suggest that several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaCbeta/CFTR mutations or variants."
The authors' own hedged conclusion: ENaC-subunit variants may impair channel function and lead to bronchiectasis, most clearly alongside a CFTR variant. It supports this node as a route into the disease and is also the basis for typing these genes as susceptibility rather than causative.
PMID:19462466 SUPPORT In vitro / ex vivo
"The p.W493R-SCNN1A polymorphism was even found to result in a four-fold more active ENaC channel when heterologously expressed in Xenopus laevis oocytes."
A heterologous-expression measurement showing that an SCNN1A variant found enriched in these patients makes the channel more active, which is the direction of effect this node asserts.
Impaired Mucociliary Clearance
Damage and dilation of airways hinder effective clearance of mucus, allowing for accumulation and further infection.
airway epithelial cell CL:0002368 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves airway epithelial cell, annotated with respiratory tract epithelial cell (CL:0002368). CL:0002368 is a cell type from the Cell Ontology. ciliated epithelial cell CL:0000067 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ciliated epithelial cell (CL:0000067). CL:0000067 is a cell type from the Cell Ontology.
SCNN1A hgnc:10599 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SCNN1A (hgnc:10599). hgnc:10599 is a gene from the HUGO Gene Nomenclature Committee.
mucociliary clearance GO:0003351 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves mucociliary clearance, annotated with epithelial cilium movement involved in extracellular fluid movement (GO:0003351). GO:0003351 is a biological process from the Gene Ontology. cilium movement GO:0003341 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves cilium movement (GO:0003341). GO:0003341 is a biological process from the Gene Ontology.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Chronic Infection and Inflammation Retained sputum creates a reservoir for persistent infection and inflammation, completing the vicious-vortex feedback loop.
Recurrent Respiratory Infections Failure to clear mucus and trapped microbes permits persistent and recurrent airway infection.
Chronic Cough Retained, hyperconcentrated airway secretions stimulate the cough reflex.
Show evidence (2 references)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia."
The review identifies ciliary dysfunction as a core bronchiectasis mechanism.
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Patients who carry the p.W493R-SCNN1A, a variant that encodes for a hyperactive ENaC channel, have been identified as being at a higher risk of developing bronchiectasis."
This human association wires hyperactive epithelial sodium-channel function to the impaired-clearance mechanism, while remaining cautious about causality and other SCNN1A variants.
Neutrophil-Driven Inflammation
Excessive neutrophil recruitment, degranulation, and NET formation release proteases (neutrophil elastase, proteinase 3, cathepsin G) that degrade extracellular matrix, impair ciliary function, and damage epithelial barriers.
neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
neutrophil degranulation GO:0043312 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves neutrophil degranulation (GO:0043312). GO:0043312 is a biological process from the Gene Ontology. neutrophil extracellular trap formation GO:0140645 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves neutrophil extracellular trap formation (GO:0140645). GO:0140645 is a biological process from the Gene Ontology. inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology. extracellular space GO:0005576 Gene Ontology (GO) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in extracellular space, annotated with extracellular region (GO:0005576). GO:0005576 is an anatomical location from the Gene Ontology.
Downstream
Protease-Antiprotease Imbalance Excessive neutrophil serine protease release overwhelms airway antiproteases, establishing the protease-antiprotease imbalance.
Show evidence (2 references)
DOI:10.1183/16000617.0179-2024 SUPPORT Other
"The excessive release of neutrophil serine proteases, such as neutrophil elastase, cathepsin G and proteinase 3, promotes a protease–antiprotease imbalance that correlates with increased inflammation in bronchiectasis and contributes to disease progression."
Direct evidence that neutrophil serine proteases drive inflammation and disease progression in bronchiectasis.
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis."
Supports NET formation as a key mechanism for protease release and disease severity.
Protease-Antiprotease Imbalance
Excess neutrophil serine proteases (NE, PR3, CatG) overwhelm antiproteases (SLPI, A1AT), degrading structural proteins and perpetuating tissue damage.
proteolysis GO:0006508 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves proteolysis (GO:0006508). GO:0006508 is a biological process from the Gene Ontology.
extracellular space GO:0005576 Gene Ontology (GO) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in extracellular space, annotated with extracellular region (GO:0005576). GO:0005576 is an anatomical location from the Gene Ontology.
Downstream
Airway Dilation Protease-driven destruction of airway-wall elastin and collagen drives the irreversible bronchial dilation.
Impaired Mucociliary Clearance Excess neutrophil elastase reduces ciliary beating and thereby weakens effective airway clearance.
Goblet Cell Hyperplasia and Mucus Hypersecretion Neutrophil elastase induces epithelial MUC5AC expression and promotes mucus hypersecretion and goblet-cell metaplasia.
Show evidence (1 reference)
DOI:10.1183/16000617.0179-2024 SUPPORT Other
"The excessive release of neutrophil serine proteases, such as neutrophil elastase, cathepsin G and proteinase 3, promotes a protease–antiprotease imbalance that correlates with increased inflammation in bronchiectasis and contributes to disease progression."
Directly supports protease-antiprotease imbalance as a neutrophil serine protease-driven mechanism linked to inflammation and bronchiectasis progression.
Goblet Cell Hyperplasia and Mucus Hypersecretion
Increased goblet cell numbers and overproduction of gel-forming mucins (MUC5AC, MUC5B) lead to mucus hyperconcentration and impaired clearance.
goblet cell CL:0000160 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves goblet cell (CL:0000160). CL:0000160 is a cell type from the Cell Ontology.
mucus secretion GO:0070254 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves mucus secretion (GO:0070254). GO:0070254 is a biological process from the Gene Ontology.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Sputum Production Overproduction of gel-forming mucins generates the copious, often purulent sputum characteristic of bronchiectasis.
Chronic Cough Excess airway mucus stimulates the cough reflex, producing the productive chronic cough.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells."
Direct support for goblet cell hyperplasia as a source of mucus symptoms in bronchiectasis.
Inflammasome Activation and IL-1beta Signaling
NLRP3 inflammasome activation drives IL-1beta production, which directly impairs ciliary function, disrupts tight junctions, promotes mucus hyperconcentration, and is associated with severe disease and Proteobacteria enrichment.
airway epithelial cell CL:0002368 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves airway epithelial cell, annotated with respiratory tract epithelial cell (CL:0002368). CL:0002368 is a cell type from the Cell Ontology.
interleukin-1 beta production GO:0032611 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves interleukin-1 beta production (GO:0032611). GO:0032611 is a biological process from the Gene Ontology.
NLRP3 inflammasome complex GO:0072559 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves NLRP3 inflammasome complex (GO:0072559). GO:0072559 is a cellular component from the Gene Ontology.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Impaired Mucociliary Clearance Chronic IL-1beta exposure compromises epithelial cilia and tight-junction function, weakening mucociliary clearance.
Show evidence (2 references)
DOI:10.1183/13993003.01966-2023 SUPPORT Human clinical
"A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction."
Cohort study (n=269) directly links airway IL-1beta to inflammasome activation, severity, and epithelial dysfunction.
DOI:10.1183/13993003.01966-2023 SUPPORT In vitro / ex vivo
"Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells"
In vitro mechanistic evidence that IL-1beta directly impairs ciliary and tight-junction function in airway epithelial cells.
Microbiome Dysbiosis
Reduced microbial diversity with Proteobacteria dominance, particularly Pseudomonas aeruginosa and Haemophilus influenzae, drives chronic infection, exacerbations, and disease progression.
bronchus UBERON:0002185 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in bronchus (UBERON:0002185). UBERON:0002185 is an anatomical location from the Uberon multi-species anatomy ontology. respiratory tract mucus UBERON:0000912 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory tract mucus, annotated with mucus (UBERON:0000912). UBERON:0000912 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Recurrent Respiratory Infections Proteobacteria-dominant dysbiosis with persistent pathogen colonization drives chronic and recurrent airway infection.
Pulmonary Exacerbations Airway resistance-gene profiles and adverse resistotypes identify patients with more frequent exacerbations and poorer outcomes.
Show evidence (3 references)
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes."
Direct support for Proteobacteria dominance as a feature of severe disease.
DOI:10.1186/s12931-024-02931-x SUPPORT Human clinical
"Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria"
Confirms reduced alpha diversity and Proteobacteria predominance via 16S rRNA sequencing of BAL samples.
DOI:10.1183/16000617.0038-2024 SUPPORT Other
"Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation."
This review directly supports microbiome–immune interplay as a central bronchiectasis mechanism.
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Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Bronchiectasis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

10
Immune 1
Recurrent Respiratory Infections FREQUENT HP:0002205 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent Respiratory Infections (HP:0002205). HP:0002205 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.1183/16000617.0179-2024 SUPPORT Human clinical
"Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life."
Recurrent respiratory infections are a hallmark clinical feature of bronchiectasis.
Respiratory 7
Chronic Cough VERY_FREQUENT HP:0034315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic Cough (HP:0034315). HP:0034315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.1183/16000617.0179-2024 SUPPORT Human clinical
"Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life."
Chronic cough is a defining clinical feature of bronchiectasis.
Sputum Production VERY_FREQUENT Increased sputum production HP:0033709 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sputum Production, annotated with Increased sputum production (HP:0033709). HP:0033709 is a phenotype from the Human Phenotype Ontology.
Often purulent and copious
Show evidence (1 reference)
DOI:10.1183/16000617.0179-2024 SUPPORT Human clinical
"Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life."
Sputum production is a defining clinical feature of bronchiectasis.
Dyspnea HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42480819 SUPPORT Other
"Bronchiectasis is a chronic respiratory condition involving a cycle of impaired mucociliary clearance, chronic infections, inflammation, and progressive airway destruction, leading to persistent cough with sputum production, dyspnea, and fatigue."
The CHEST guideline identifies dyspnea among the clinical consequences of the bronchiectasis disease cycle.
Hemoptysis HP:0002105 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hemoptysis (HP:0002105). HP:0002105 is a phenotype from the Human Phenotype Ontology.
Blood in cough due to airway damage
Show evidence (1 reference)
PMID:7555168 SUPPORT Human clinical
"Symptoms of bronchiectasis included chronic cough with the production of purulent sputum, hemoptysis, recurrent fever, and pleurisy."
The 123-patient cohort directly documents hemoptysis as a bronchiectasis symptom; no frequency band is assigned because the abstract does not quantify it.
Fixed Airflow Obstruction Chronic pulmonary obstruction HP:0006510 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic pulmonary obstruction (HP:0006510). HP:0006510 is a phenotype from the Human Phenotype Ontology.
Progressive airflow limitation that may develop in bronchiectasis patients, associated with Proteobacteria-enriched microbiome
Show evidence (1 reference)
DOI:10.1186/s12931-024-02931-x SUPPORT Human clinical
"compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations."
Direct evidence that fixed airflow obstruction is a clinically relevant phenotype in bronchiectasis with worse outcomes.
Wheezing FREQUENT HP:0030828 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Wheezing (HP:0030828). HP:0030828 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:7555168 SUPPORT Human clinical
"The finding of crackles on chest examination was the rule (70%) with wheezing present in 34% of the group."
Wheezing occurred in 34% of this 123-patient cohort, which falls in the FREQUENT (30-79%) band.
Crackles FREQUENT HP:0030830 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Crackles (HP:0030830). HP:0030830 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:7555168 SUPPORT Human clinical
"The finding of crackles on chest examination was the rule (70%) with wheezing present in 34% of the group."
Crackles occurred in 70% of this 123-patient cohort, which falls in the FREQUENT (30-79%) band.
Constitutional 1
Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42480819 SUPPORT Other
"Bronchiectasis is a chronic respiratory condition involving a cycle of impaired mucociliary clearance, chronic infections, inflammation, and progressive airway destruction, leading to persistent cough with sputum production, dyspnea, and fatigue."
The CHEST guideline explicitly includes fatigue among the clinical consequences of bronchiectasis.
Other 1
Pulmonary Exacerbations
Acute worsening typically includes increased cough and sputum and worsened fatigue, and is associated with lung-function decline and lower quality of life.
Show evidence (1 reference)
PMID:40293759 SUPPORT Other
"Exacerbations of bronchiectasis, which typically present with increased cough and sputum and worsened fatigue, are associated with progressive decline in lung function and decreased quality of life."
The review directly defines the exacerbation phenotype and its major clinical consequences.
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Genetic Associations

3
CFTR (Modifier gene)
Gene: CFTR hgnc:1884 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CFTR (hgnc:1884). hgnc:1884 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"These studies highlight that the role of CFTR in bronchiectasis remains contentious and that further multicenter studies on larger cohorts of patients are needed to resolve this debate."
The review explicitly characterizes the human CFTR association as unresolved, so this is retained only as a proposed modifier.
SCNN1A (Susceptibility gene)
Gene: SCNN1A hgnc:10599 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SCNN1A (hgnc:10599). hgnc:10599 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (3 references)
PMID:19462466 SUPPORT Human clinical
"In a small fraction of the patients, the disease could be potentially explained by an ENaC mutation by a Mendelian mechanism, such as p.V114I and p.F61L in SCNN1A."
Names the two SCNN1A alleles the authors consider potentially Mendelian, and the hedging plus "small fraction" is why this record is typed SUSCEPTIBILITY.
PMID:19462466 SUPPORT Human clinical
"Specifically, a significantly higher number of patients carried c.-55+5G>C or p.W493R in SCNN1A in the heterozygous state, with odds ratios (ORs) of 13.5 and 2.7, respectively."
The case-control association for two heterozygous SCNN1A variants, which is a susceptibility observation rather than evidence of segregation.
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Patients who carry the p.W493R-SCNN1A, a variant that encodes for a hyperactive ENaC channel, have been identified as being at a higher risk of developing bronchiectasis."
The review reports human susceptibility evidence for one SCNN1A variant; this does not establish broad causality for all SCNN1A variation.
SCNN1G (Susceptibility gene)
Gene: SCNN1G hgnc:10602 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SCNN1G (hgnc:10602). hgnc:10602 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:18507830 SUPPORT Human clinical
"Sequencing of the exons and flanking introns of the ENaCbeta and gamma gene identified five different amino-acid changes"
The variant discovery this record rests on, in a cohort selected for idiopathic bronchiectasis without two CFTR coding mutations.
PMID:18507830 SUPPORT Human clinical
"Our results suggest that several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaCbeta/CFTR mutations or variants."
The authors' conclusion, which is hedged and conditions the effect on a concurrent CFTR variant; this is the basis for the SUSCEPTIBILITY typing.
💊

Medical Actions

12
Airway Clearance Techniques
Action: physical therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is physical therapy (NCIT:C15302). NCIT:C15302 is a clinical intervention from the NCI Thesaurus. Ontology label: Physical Therapy NCIT:C15302
Platform: Behavioral / lifestyle
Physical therapies to enhance mucus clearance, such as chest physiotherapy.
Show evidence (1 reference)
PMID:41016738 SUPPORT Other
"The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis, and pulmonary rehabilitation for those with impaired exercise capacity."
The primary European Respiratory Society clinical practice guideline makes a strong recommendation in favour of airway clearance techniques for most patients with bronchiectasis.
Pulmonary Rehabilitation
Action: physical therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is physical therapy (NCIT:C15302). NCIT:C15302 is a clinical intervention from the NCI Thesaurus. Ontology label: Physical Therapy NCIT:C15302
Platform: Behavioral / lifestyle
Exercise-based pulmonary rehabilitation is recommended for patients with impaired exercise capacity.
Show evidence (1 reference)
PMID:41016738 SUPPORT Other
"The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis, and pulmonary rehabilitation for those with impaired exercise capacity."
The ERS guideline strongly recommends pulmonary rehabilitation for the exercise-limited subgroup.
Antibiotic Treatment of Acute Exacerbations
Action: antibiotic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antibiotic therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Platform: Small molecule
Antibiotics are used for acute bronchiectasis exacerbations, with agent, route, and duration selected from clinical severity and microbiology.
Show evidence (1 reference)
PMID:42480819 SUPPORT INDIRECT Other
"Based on 47 studies, the panel developed 13 evidence-based recommendations addressing key management domains, including antibiotic treatment for acute exacerbations, duration and route of antibiotic therapy, long-term suppressive antibiotic and anti-inflammatory therapies, airway clearance..."
The abstract establishes that the guideline addresses antibiotic treatment, route, and duration, but does not expose the direction or certainty of the individual recommendation.
Long-term Macrolide Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: azithromycin CHEBI:2955 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses azithromycin (CHEBI:2955). CHEBI:2955 is a therapeutic agent from Chemical Entities of Biological Interest. erythromycin CHEBI:48923 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses erythromycin (CHEBI:48923). CHEBI:48923 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Maintenance macrolide antibiotics such as azithromycin or erythromycin reduce pulmonary exacerbations in selected patients, while requiring attention to macrolide resistance risk.
Show evidence (2 references)
PMID:22901887 SUPPORT Human clinical
"Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year."
EMBRACE was a randomized, double-blind, placebo-controlled trial supporting azithromycin for exacerbation prevention.
PMID:23532242 SUPPORT Human clinical
"Among patients with non-CF bronchiectasis, the 12-month use of erythromycin compared with placebo resulted in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance."
BLESS supports long-term macrolide therapy reducing exacerbations while also documenting resistance risk.
Long-Term Inhaled Antibiotic Therapy
Action: antibiotic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antibiotic therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Platform: Small molecule
Long-term inhaled antibiotics are recommended for patients with chronic Pseudomonas aeruginosa infection who remain at high exacerbation risk.
Show evidence (1 reference)
PMID:41016738 SUPPORT Other
"We issue a strong recommendation for the use of long-term macrolide treatment for patients at high risk of exacerbations and a strong recommendation in favour of long-term inhaled antibiotics in patients with chronic Pseudomonas aeruginosa infection at high risk of exacerbation."
The ERS guideline makes a strong recommendation for inhaled antibiotics in this defined high-risk subgroup.
Pathogen Eradication Therapy
Action: antibiotic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antibiotic therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Platform: Small molecule
Targeted eradication treatment may be used in selected circumstances after identifying a clinically important airway pathogen.
Show evidence (1 reference)
PMID:41016738 SUPPORT Other
"Conditional recommendations support the use of eradication treatment or mucoactive drugs in specific circumstances."
The guideline conditionally supports eradication therapy but the abstract does not define every eligible pathogen or clinical circumstance.
Mucoactive Therapy
Action: respiratory tract agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is respiratory tract agent therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Platform: Other
Nebulized saline and other mucoactive drugs may be used in selected patients to loosen tenacious secretions and support airway clearance.
Show evidence (2 references)
PMID:40293759 SUPPORT Other
"nebulization of saline to loosen tenacious secretions"
The clinical review explicitly includes nebulized saline for loosening tenacious bronchiectasis secretions.
DOI:10.1183/13993003.01689-2023 SUPPORT Human clinical
"Mucoactive drugs were also more likely to be used in participants with more severe disease."
EMBARC documents real-world mucoactive-drug use, especially in more severe disease, but does not by itself establish comparative efficacy.
Brensocatib
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: Brensocatib NCIT:C171778 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Brensocatib (NCIT:C171778). NCIT:C171778 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Oral reversible dipeptidyl peptidase 1 inhibitor that reduces neutrophil serine protease activity and pulmonary exacerbations.
Mechanism Target:
INHIBITS Protease-Antiprotease Imbalance — Brensocatib inhibits DPP-1, targeting neutrophil serine proteases that drive the protease-antiprotease imbalance.
Show evidence (1 reference)
PMID:40267423 SUPPORT Human clinical
"Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation."
The ASPEN trial abstract describes brensocatib's DPP-1 inhibition as targeting neutrophil serine proteases.
Show evidence (1 reference)
PMID:40267423 SUPPORT Human clinical
"Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1 was less with the 25-mg dose of brensocatib than with placebo."
ASPEN was a phase 3, double-blind trial demonstrating reduced pulmonary exacerbations with once-daily brensocatib.
Surgery
Action: surgical procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is surgical procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Platform: Surgery
Surgical resection may be considered for selected patients after multidisciplinary assessment; it is not routine bronchiectasis treatment.
Show evidence (2 references)
PMID:42480819 SUPPORT INDIRECT Other
"Based on 47 studies, the panel developed 13 evidence-based recommendations addressing key management domains, including antibiotic treatment for acute exacerbations, duration and route of antibiotic therapy, long-term suppressive antibiotic and anti-inflammatory therapies, airway clearance..."
The abstract establishes that selected-patient resection is addressed, but does not expose the direction or certainty of the recommendation.
DOI:10.1055/s-0041-1730891 SUPPORT Other
"removing damaging areas of the lung through surgery"
Names resection of damaged lung as one of the approaches directed at the consequences of structural lung damage, which is the rationale this treatment entry records.
Bronchodilators for Airflow Obstruction
Action: bronchodilator therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is bronchodilator therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: bronchodilator NCIT:C319 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses bronchodilator (NCIT:C319). NCIT:C319 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Bronchodilators may be used to treat airflow obstruction as a consequence of structural lung disease; the review does not establish routine benefit for every patient with bronchiectasis.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT INDIRECT Other
"Most approaches therefore aim to deal with the consequences of structural lung damage, such as treating air flow obstruction with bronchodilators"
Names bronchodilators as the treatment directed at airflow obstruction. The review states the therapeutic aim rather than a comparative result, so the support for using them in a given patient is inferential.
Routine Inhaled Corticosteroids
Action: respiratory tract agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is respiratory tract agent therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Platform: Small molecule
Inhaled corticosteroids should not be used routinely for bronchiectasis alone; separate indications such as severe asthma or allergic bronchopulmonary aspergillosis require individualized management.
Show evidence (1 reference)
PMID:41016738 REFUTE Other
"We suggest not to routinely use long-term oral, non-macrolide antibiotic treatment or inhaled corticosteroids."
The ERS guideline explicitly advises against routine inhaled corticosteroids in adults with bronchiectasis.
Vaccinations
Action: VaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. NCIT:C15346
Platform: Vaccine
Prevent respiratory infections and exacerbations.
🌍

Environmental Factors

2
Pollution
Air pollution exposure ECTO:8000036 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is Air pollution exposure, annotated with exposure to air pollution (ECTO:8000036). ECTO:8000036 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Short-term sulfur-dioxide exposure was associated with emergency visits for bronchiectasis exacerbations in one retrospective study.
Show evidence (1 reference)
PMID:29772571 SUPPORT Human clinical
"The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2."
This retrospective observational study supports an association between sulfur-dioxide exposure and bronchiectasis exacerbation visits.
Smoking
Tobacco smoking exposure ECTO:6000029 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is Tobacco smoking exposure, annotated with exposure to tobacco smoking (ECTO:6000029). ECTO:6000029 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
In one clinical cohort, patients who had smoked showed greater airway obstruction than nonsmokers, while otherwise having a similar clinical picture.
Show evidence (2 references)
PMID:7555168 SUPPORT Human clinical
"Patients who had smoked had much the same picture as nonsmokers, although they had a greater degree of airway obstruction."
The cohort directly associates prior smoking with greater airway obstruction without implying broad causation of bronchiectasis.
PMID:38888096 SUPPORT Human clinical
"This review emphasizes the role of smoking in bronchiectasis development and exacerbation by compromising airways and immune function."
Review of the clinical literature supporting smoking as a driver of bronchiectasis development and exacerbation.
🔬

Biochemical Markers

6
Bronchiectasis Biomarker Profiles (Variable)
Context: Inflammatory, microbiome, radiologic, mucus, and epithelial measurements define heterogeneous profiles being investigated for prognosis and treatment selection; no single profile is universally diagnostic.
Show evidence (1 reference)
DOI:10.1183/16000617.0234-2023 SUPPORT Other
"Increasingly there are available methods to measure each of these components of the disease, revealing heterogeneous inflammatory profiles, microbiota, radiology and mucus and epithelial biology in patients with bronchiectasis."
The biomarker review supports heterogeneous measurable disease profiles rather than a single universal biomarker.
C-Reactive Protein (CRP) (Elevated)
Context: Serum CRP can be elevated in infection-associated bronchiectasis, including Haemophilus influenzae-dominant disease; it is nonspecific.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"an increase in serum CRP"
The cited association supports elevated CRP in an infection-defined subgroup, not as a specific or universal bronchiectasis marker.
Sputum Culture (Positive)
Context: Identifies clinically actionable airway organisms, although conventional culture is insensitive and a negative result does not exclude infection.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"sputum culture is a critical component"
The review directly supports sputum culture as an actionable assessment biomarker while noting its limited sensitivity.
Neutrophil Elastase (NE) (Elevated)
Context: High sputum NE activity associates with severe bronchiectasis, exacerbation risk, airway bacterial load, and disease progression; mechanistic biomarker of neutrophil-driven inflammation
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes."
Supports elevated neutrophil elastase as a biomarker linked to worse outcomes in bronchiectasis.
Interleukin-1 beta (IL-1beta) (Elevated)
Context: Subset of patients with high airway IL-1beta show severe disease, mucus hyperconcentration, impaired ciliary function, and Proteobacteria-enriched microbiome
Show evidence (1 reference)
DOI:10.1183/13993003.01966-2023 SUPPORT Human clinical
"Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β."
Cohort study links elevated airway IL-1beta to greater severity and amplified inflammatory response.
Neutrophil Extracellular Traps (NETs) (Elevated)
Context: NET complexes in sputum associate with higher disease severity, exacerbations, and mortality; include MPO, NE, resistin, and azurocidin
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Human clinical
"Our study found that NETs were present in sputum of patients with bronchiectasis and correlated with increasing severity, mortality, severe exacerbation, and a reduction in time to next exacerbation."
The review reports multicohort sputum evidence linking NET abundance to severity, exacerbations, and mortality.
🔬

Diagnosis

2
High-Resolution CT Scan
Thin-section chest CT demonstrates permanent bronchial dilation and establishes the defining radiologic abnormality.
computed tomography procedure NCIT:C17204 NCI Thesaurus (NCIT)
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"AbstractBronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome."
The review establishes permanent bronchial dilation on imaging as one of the two defining components of bronchiectasis.
Pulmonary Function Test
Pulmonary function testing characterizes airflow obstruction and supports severity assessment, but it does not establish the structural diagnosis. FEV1 as a percentage of predicted is the lung-function component of both multidimensional severity scores: the Bronchiectasis Severity Index (BSI) selected it as the most discriminatory lung-function measure for mortality and hospital admission, and the FACED score dichotomises it at a 50% cut-off for its F component.
pulmonary function testing NCIT:C38081 NCI Thesaurus (NCIT)
FEV1 percent predicted LOINC:20152-5 Logical Observation Identifiers Names and Codes (LOINC)
Reference Ranges
FEV1 measured/predicted (FACED score derivation and validation cohorts, 2014 (non-cystic fibrosis bronchiectasis))
FACED F component, FEV1 below the 50% cut-off (< 50.0 %) FACED F component, FEV1 at or above the 50% cut-off (≥ 50.0 %)
FACED F component, FEV1 below the 50% cut-off: Lower FEV1 stratum of the FACED F component; the component contributes up to 2 of the score's 7 points.
FACED F component, FEV1 at or above the 50% cut-off: Upper FEV1 stratum of the FACED F component. NORMAL here means the component is not contributing to severity, not that the value sits in a population reference interval, which this row does not record.
The abstract states the F component as "forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points)" and does not say in its own text which side of the cut-off scores the points or on which side a value of exactly 50% falls; the bands partition the scale at the stated cut-off, and the lower stratum is flagged as the abnormal one because the score classifies severity by prognosis and the component's points are a severity contribution. Read the band names as the two F strata, not as a statement of the points each receives. The BSI derivation paper (PMID:24328736, full text cached without its tables) names FEV1 below 30% predicted as an independent predictor of hospital admission but its multi-stratum FEV1 point table is not in the cached prose, so no BSI bands are recorded.
Show evidence (2 references)
PMID:24232697 SUPPORT PRIMARY RESULT Human clinical
"The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points)"
States the FEV1 percent-predicted cut-off reproduced as the band boundary below and the maximum points the F component contributes.
PMID:24232697 SUPPORT PRIMARY RESULT Human clinical
"The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis."
The score grades severity by prognosis, which is the basis on which the lower FEV1 stratum is flagged as the abnormal band.
Identity is bound at the method-less code for FEV1 as measured over predicted (LOINC:20152-5), the form both severity scores use; the FEV1 volume and the FEV1/FVC ratio are not bound because neither score grades on them.
Show evidence (3 references)
PMID:24328736 SUPPORT PRIMARY RESULT Human clinical
"Based on the Youden index, FEV1 % predicted was most discriminatory for mortality and hospital admissions and was used for subsequent analyses of lung function."
The BSI derivation selected FEV1 percent predicted over the ratio and FVC as its lung-function measure, which is why that quantity is the measurement bound on this row.
PMID:24328736 SUPPORT PRIMARY RESULT Human clinical
"Independent of this, Medical Research Council dyspnea score, FEV1 less than 30% predicted, and colonization with P. aeruginosa or other organisms were independent predictors of hospital admissions."
The one FEV1 threshold the BSI paper states in its prose; recorded as evidence that FEV1 percent predicted carries a severity threshold in that score, with the full BSI point table left unbanded as the range notes explain.
PMID:7555168 SUPPORT Human clinical
"Pulmonary function studies documented airway obstruction to be present in 54% of the lifetime nonsmokers."
The cohort shows that pulmonary function testing identifies airflow obstruction in a substantial bronchiectasis subgroup.
📈

Progression

1
Variable onset and progressive structural lung damage
Age: Childhood through adulthood
Bronchiectasis can arise in children or adults from heterogeneous causes. Chronic inflammation, infection, and mucus obstruction can drive progressive structural injury after disease begins.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage."
The review supports progressive structural damage but does not define a uniform age-specific natural history.
📊

Prevalence

3
Reported populations worldwide
Point prevalence ≤566 per 100,000 >1 in 1,000
This is the upper end of published population estimates summarized by the review, not a single worldwide point estimate. Rates vary substantially by population, age, ascertainment, and calendar period.
Show evidence (1 reference)
DOI:10.1055/s-0041-1730891 SUPPORT Other
"the incidence and prevalence of bronchiectasis has increased 40% in the past 10 years throughout the world, with rates of up to 566 per 100,000 population being reported."
The review supplies the maximum reported population rate represented here; the notes prevent interpreting it as a universal prevalence.
US adults aged 18-34 years
Point prevalence 7 per 100,000 1–9 per 100,000
Show evidence (1 reference)
PMID:40293759 SUPPORT Other
"The prevalence of non-CF bronchiectasis increases substantially with age (7 per 100 000 in individuals 18-34 years vs 812 per 100 000 in those ≥75 years)"
The review reports an age-specific US prevalence of 7 per 100,000 among adults aged 18-34 years.
US adults aged 75 years and older
Point prevalence 812 per 100,000 >1 in 1,000
Show evidence (1 reference)
PMID:40293759 SUPPORT Other
"The prevalence of non-CF bronchiectasis increases substantially with age (7 per 100 000 in individuals 18-34 years vs 812 per 100 000 in those ≥75 years)"
The review reports an age-specific US prevalence of 812 per 100,000 among adults aged 75 years and older.
📊

Related Datasets

6
Single-cell RNA-sequencing of bronchoalveolar lavage cells from humans with bronchiectasis geo:GSE217516
Bronchiectasis is a lung disease characterized by irreversible dilation of the large airways (bronchodilatation), which often causes recurrent airway infection and non-resolving inflammation. In this study, we performed single-cell RNA-sequencing (scRNA-seq) to determine the heterogeneity of immune cells in the airways of bronchiectasis patients.
human SINGLE CELL RNA SEQ n=6
PMID:41774079
Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial geo:GSE261102
Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients.
human BULK RNA SEQ n=7
PMID:39566467
Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium geo:GSE302095
Objectives: Examination of bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. Methods: We studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) was used to examine whether genes previously identified as increased or decreased in the bronchial epithelium of individuals with radiologic BE are significantly enriched among the genes most significantly altered in the nasal epithelium.
human BULK RNA SEQ n=132
PMID:42094231
Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Integrated Single-Cell and Microbiome Profiling of Stable Bronchiectasis Across Disease Severity ega:EGAS50000001808
Bronchiectasis is a chronic respiratory disease characterized by persistent airway inflammation and recurrent infections. In this study, sputum samples from patients with mild, moderate, and severe bronchiectasis, collected during clinically stable disease, were analyzed using flow cytometry, single-cell RNA sequencing, and 16S rRNA gene sequencing. The resulting datasets enable characterization of neutrophil populations, transcriptional states, and airway microbial communities across disease severity stages.
human
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Bronchiectasis"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
NHLBI GO-ESP Family Studies: Idiopathic Bronchiectasis dbgap:phs000518
The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied.
Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Bronchiectasis"). Retrieved 2026-08-02.
Cross-Sectional Characterization of Idiopathic Bronchiectasis dbgap:phs001279
This GDMCC protocol will study adult patients with non-CF, idiopathic bronchiectasis, whose genetic etiologies are not known. Idiopathic bronchiectasis is reportedly more common in females with certain tall, thin body types and associated with environmental organisms, such as nontuberculous mycobacterium (NTM). The other susceptibility factors predisposing to bronchiectasis or acquisition of NTM are unclear. The study will attempt to broaden the understanding of this disease by comparing gender-associated factors and NTM status.
Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Bronchiectasis"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Bronchiectasis
creation_date: '2025-12-04T16:57:31Z'
category: Respiratory Disease
description: >-
  Bronchiectasis is a chronic respiratory disease characterized by permanent, abnormal
  dilation and thickening of the bronchi resulting from a self-perpetuating cycle of airway
  infection, inflammation, impaired mucociliary clearance, and progressive structural lung
  damage (the so-called vicious vortex). It may be idiopathic or arise secondary to prior
  severe respiratory infection, cystic fibrosis, primary ciliary dyskinesia, immunodeficiency,
  allergic bronchopulmonary aspergillosis, or chronic obstructive airway disease. Affected
  individuals experience chronic productive cough, recurrent respiratory infections, and
  progressive airflow obstruction, with acute exacerbations driving stepwise decline in lung
  function.
parents:
- Chronic Lung Disease
- Inflammatory Lung Disease
prevalence:
- population: Reported populations worldwide
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_high: 566
  notes: >-
    This is the upper end of published population estimates summarized by the
    review, not a single worldwide point estimate. Rates vary substantially by
    population, age, ascertainment, and calendar period.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the incidence and prevalence of bronchiectasis has increased 40% in the
      past 10 years throughout the world, with rates of up to 566 per 100,000
      population being reported.
    explanation: >-
      The review supplies the maximum reported population rate represented
      here; the notes prevent interpreting it as a universal prevalence.
- population: US adults aged 18-34 years
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 7
  evidence:
  - reference: PMID:40293759
    reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The prevalence of non-CF bronchiectasis increases substantially with age
      (7 per 100 000 in individuals 18-34 years vs 812 per 100 000 in those ≥75
      years)
    explanation: >-
      The review reports an age-specific US prevalence of 7 per 100,000 among
      adults aged 18-34 years.
- population: US adults aged 75 years and older
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 812
  evidence:
  - reference: PMID:40293759
    reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The prevalence of non-CF bronchiectasis increases substantially with age
      (7 per 100 000 in individuals 18-34 years vs 812 per 100 000 in those ≥75
      years)
    explanation: >-
      The review reports an age-specific US prevalence of 812 per 100,000 among
      adults aged 75 years and older.
progression:
- phase: Variable onset and progressive structural lung damage
  age_range: Childhood through adulthood
  notes: >-
    Bronchiectasis can arise in children or adults from heterogeneous causes.
    Chronic inflammation, infection, and mucus obstruction can drive
    progressive structural injury after disease begins.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The contribution of chronic inflammation, infection, and mucus
      obstruction leads to progressive structural lung damage.
    explanation: >-
      The review supports progressive structural damage but does not define a
      uniform age-specific natural history.
pathophysiology:
- name: Chronic Infection and Inflammation
  description: Persistent microbial infections and inflammation damage airway walls, leading to dilation and thickening.
  evidence:
  - reference: DOI:10.1183/16000617.0055-2024
    reference_title: 'Pathophysiology and genomics of bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology.
    explanation: Vicious vortex model centers on chronic infection plus inflammation as the core pathophysiology of bronchiectasis.
  downstream:
  - target: Neutrophil-Driven Inflammation
    description: >-
      Persistent airway infection and higher bacterial burden sustain the
      characteristic neutrophilic inflammatory response.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Neutrophilic inflammation is associated with elevated bacterial loads
        and chronic infection with organisms such as Pseudomonas aeruginosa.
      explanation: >-
        The review directly associates chronic airway infection and bacterial
        burden with neutrophilic inflammation.
  - target: Airway Dilation
    description: >-
      Persistent infection, inflammation, and mucus obstruction cause
      progressive structural airway damage that culminates in irreversible
      bronchial dilation.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The contribution of chronic inflammation, infection, and mucus
        obstruction leads to progressive structural lung damage.
      explanation: >-
        The review directly links the interacting inflammatory, infectious, and
        mucus-obstruction components to progressive structural damage.
  - target: Pulmonary Exacerbations
    description: >-
      Recurrent increases in infection and inflammation manifest clinically as
      pulmonary exacerbations.
    evidence:
    - reference: PMID:40293759
      reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Exacerbations of bronchiectasis, which typically present with increased
        cough and sputum and worsened fatigue, are associated with progressive
        decline in lung function and decreased quality of life.
      explanation: >-
        The review defines the clinical exacerbation outcome and its sequelae;
        the infection-to-exacerbation transition is not isolated experimentally.
  - target: Fatigue
    description: >-
      The chronic disease burden and exacerbation episodes contribute to
      clinically important fatigue.
    evidence:
    - reference: PMID:40293759
      reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Exacerbations of bronchiectasis, which typically present with increased
        cough and sputum and worsened fatigue, are associated with progressive
        decline in lung function and decreased quality of life.
      explanation: >-
        The review identifies worsened fatigue during exacerbations; this edge
        represents a clinical output rather than an isolated causal experiment.
- name: Airway Dilation
  description: Destruction of elastin and cartilage in the bronchial walls causes irreversible dilation of bronchi.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "AbstractBronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome."
    explanation: >-
      The review identifies permanent bronchial dilation as the defining
      structural abnormality.
  downstream:
  - target: Impaired Mucociliary Clearance
  - target: Fixed Airflow Obstruction
    description: Irreversible structural destruction and dilation of the bronchial walls produces the progressive, fixed airflow limitation seen in bronchiectasis.
  - target: Dyspnea
    description: Airway structural damage and airflow limitation manifest clinically as breathlessness.
  - target: Wheezing
    description: Distorted, dilated airways and luminal narrowing during airflow produce wheeze.
  - target: Hemoptysis
    description: Bronchial wall destruction with hypertrophied, fragile bronchial
      arteries predisposes to airway bleeding.
  - target: Crackles
    description: >-
      Distorted, secretion-filled airways generate discontinuous adventitious
      sounds on auscultation.
    evidence:
    - reference: PMID:7555168
      reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The finding of crackles on chest examination was the rule (70%) with
        wheezing present in 34% of the group.
      explanation: >-
        The cohort establishes crackles as a frequent clinical output; the
        structural airway-to-sound mechanism is not isolated experimentally.
- name: Airway Surface Liquid Dehydration
  description: >-
    An epithelial ion-transport route into the vicious vortex, separate from the
    infection-driven route. Hyperactive epithelial sodium channel (ENaC) function
    increases sodium absorption across the airway epithelium and draws water out
    of the airway surface liquid; reduced CFTR-mediated chloride and fluid
    secretion acts in the same direction. The resulting dehydrated, viscous
    surface liquid impairs mucus transport, which is why variants in the ENaC
    subunit genes are found in idiopathic bronchiectasis and why the effect is
    clearest in patients who also carry a CFTR variant.
  cell_types:
  - preferred_term: airway epithelial cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  genes:
  - preferred_term: SCNN1A
    term:
      id: hgnc:10599
      label: SCNN1A
  - preferred_term: SCNN1G
    term:
      id: hgnc:10602
      label: SCNN1G
  - preferred_term: CFTR
    term:
      id: hgnc:1884
      label: CFTR
  molecular_functions:
  - preferred_term: amiloride-sensitive sodium channel (ENaC) activity
    modifier: GAIN_OF_FUNCTION
    term:
      id: GO:0015280
      label: ligand-gated sodium channel activity
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
  evidence:
  - reference: PMID:18507830
    reference_title: "Could a defective epithelial sodium channel lead to bronchiectasis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our results suggest that several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaCbeta/CFTR mutations or variants."
    explanation: >-
      The authors' own hedged conclusion: ENaC-subunit variants may impair
      channel function and lead to bronchiectasis, most clearly alongside a CFTR
      variant. It supports this node as a route into the disease and is also the
      basis for typing these genes as susceptibility rather than causative.
  - reference: PMID:19462466
    reference_title: "Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The p.W493R-SCNN1A polymorphism was even found to result in a four-fold more active ENaC channel when heterologously expressed in Xenopus laevis oocytes."
    explanation: >-
      A heterologous-expression measurement showing that an SCNN1A variant found
      enriched in these patients makes the channel more active, which is the
      direction of effect this node asserts.
  downstream:
  - target: Impaired Mucociliary Clearance
    causal_link_type: DIRECT
    description: >-
      A dehydrated, hyperconcentrated periciliary layer prevents effective
      ciliary mucus transport, feeding the same clearance failure that airway
      dilation produces by a structural route.
- name: Impaired Mucociliary Clearance
  description: Damage and dilation of airways hinder effective clearance of mucus, allowing for accumulation and further infection.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Ciliary dysfunction is also a key feature, exemplified by the rare genetic
      syndrome of primary ciliary dyskinesia.
    explanation: >-
      The review identifies ciliary dysfunction as a core bronchiectasis
      mechanism.
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients who carry the p.W493R-SCNN1A, a variant that encodes for a
      hyperactive ENaC channel, have been identified as being at a higher risk
      of developing bronchiectasis.
    explanation: >-
      This human association wires hyperactive epithelial sodium-channel
      function to the impaired-clearance mechanism, while remaining cautious
      about causality and other SCNN1A variants.
  downstream:
  - target: Chronic Infection and Inflammation
    description: >-
      Retained sputum creates a reservoir for persistent infection and
      inflammation, completing the vicious-vortex feedback loop.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Dysfunctional mucociliary clearance can lead to sputum retention in the
        airways, creating a harbor for infection
      explanation: >-
        The review directly links failed clearance to retained sputum and a
        permissive environment for infection. The quote stops before the
        source's next word, which the PDF text renders with an fl ligature.
  - target: Recurrent Respiratory Infections
    description: Failure to clear mucus and trapped microbes permits persistent and recurrent airway infection.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The pathophysiology of disease is understood in terms of interdependent
        concepts of chronic infection, inflammation, impaired mucociliary
        clearance, and structural lung damage.
      explanation: >-
        The review supports the interdependence of impaired clearance and
        chronic infection; it does not isolate this edge experimentally.
  - target: Chronic Cough
    description: Retained, hyperconcentrated airway secretions stimulate the cough reflex.
  cell_types:
  - preferred_term: airway epithelial cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  - preferred_term: ciliated epithelial cell
    term:
      id: CL:0000067
      label: ciliated epithelial cell
  genes:
  - preferred_term: SCNN1A
    term:
      id: hgnc:10599
      label: SCNN1A
  biological_processes:
  - preferred_term: mucociliary clearance
    term:
      id: GO:0003351
      label: epithelial cilium movement involved in extracellular fluid movement
  - preferred_term: cilium movement
    term:
      id: GO:0003341
      label: cilium movement
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
- name: Neutrophil-Driven Inflammation
  description: Excessive neutrophil recruitment, degranulation, and NET formation release proteases (neutrophil elastase, proteinase 3, cathepsin G) that degrade extracellular matrix, impair ciliary function, and damage epithelial barriers.
  downstream:
  - target: Protease-Antiprotease Imbalance
    description: Excessive neutrophil serine protease release overwhelms airway antiproteases, establishing the protease-antiprotease imbalance.
    evidence:
    - reference: DOI:10.1183/16000617.0179-2024
      reference_title: Neutrophilic inflammation in bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The excessive release of neutrophil serine proteases, such as
        neutrophil elastase, cathepsin G and proteinase 3, promotes a
        protease–antiprotease imbalance that correlates with increased
        inflammation in bronchiectasis and contributes to disease progression.
      explanation: >-
        The review directly links neutrophil serine-protease release to the
        protease-antiprotease imbalance.
  evidence:
  - reference: DOI:10.1183/16000617.0179-2024
    reference_title: 'Neutrophilic inflammation in bronchiectasis'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: The excessive release of neutrophil serine proteases, such as neutrophil elastase, cathepsin G and proteinase 3, promotes a protease–antiprotease imbalance that correlates with increased inflammation in bronchiectasis and contributes to disease progression.
    explanation: Direct evidence that neutrophil serine proteases drive inflammation and disease progression in bronchiectasis.
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: 'Pathophysiology of Bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis.
    explanation: Supports NET formation as a key mechanism for protease release and disease severity.
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: neutrophil degranulation
    term:
      id: GO:0043312
      label: neutrophil degranulation
  - preferred_term: neutrophil extracellular trap formation
    term:
      id: GO:0140645
      label: neutrophil extracellular trap formation
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
  - preferred_term: extracellular space
    term:
      id: GO:0005576
      label: extracellular region
- name: Protease-Antiprotease Imbalance
  description: Excess neutrophil serine proteases (NE, PR3, CatG) overwhelm antiproteases (SLPI, A1AT), degrading structural proteins and perpetuating tissue damage.
  conforms_to: emphysema_protease_antiprotease_imbalance#Protease-Antiprotease Imbalance
  downstream:
  - target: Airway Dilation
    description: Protease-driven destruction of airway-wall elastin and collagen drives the irreversible bronchial dilation.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        NE can damage the extracellular matrix
      explanation: >-
        The review directly supports extracellular-matrix damage by neutrophil
        elastase; the final transition to macroscopic dilation remains an
        inferred structural consequence.
  - target: Impaired Mucociliary Clearance
    description: >-
      Excess neutrophil elastase reduces ciliary beating and thereby weakens
      effective airway clearance.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        NE can damage the extracellular matrix and reduce ciliary beat
        frequency
      explanation: >-
        The review directly links neutrophil elastase activity to reduced
        ciliary beat frequency; the same sentence continues that this reduces
        effective clearance, a word the PDF text hyphenates across a line
        break, so the quote stops before it.
  - target: Goblet Cell Hyperplasia and Mucus Hypersecretion
    description: >-
      Neutrophil elastase induces epithelial MUC5AC expression and promotes
      mucus hypersecretion and goblet-cell metaplasia.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        In vitro, NE increases the expression of MUC5AC from bronchial
        epithelial cells
      explanation: >-
        Cell-culture evidence directly supports NE-induced epithelial MUC5AC
        expression.
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        studies in murine models have demonstrated that NE increases mucus
        hypersecretion and goblet cell metaplasia, hampering effective
        mucociliary clearance.
      explanation: >-
        Murine-model evidence supports NE-driven mucus hypersecretion and
        goblet-cell metaplasia.
  evidence:
  - reference: DOI:10.1183/16000617.0179-2024
    reference_title: 'Neutrophilic inflammation in bronchiectasis'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: The excessive release of neutrophil serine proteases, such as neutrophil elastase, cathepsin G and proteinase 3, promotes a protease–antiprotease imbalance that correlates with increased inflammation in bronchiectasis and contributes to disease progression.
    explanation: Directly supports protease-antiprotease imbalance as a neutrophil serine protease-driven mechanism linked to inflammation and bronchiectasis progression.
  biological_processes:
  - preferred_term: proteolysis
    term:
      id: GO:0006508
      label: proteolysis
  locations:
  - preferred_term: extracellular space
    term:
      id: GO:0005576
      label: extracellular region
- name: Goblet Cell Hyperplasia and Mucus Hypersecretion
  description: Increased goblet cell numbers and overproduction of gel-forming mucins (MUC5AC, MUC5B) lead to mucus hyperconcentration and impaired clearance.
  downstream:
  - target: Sputum Production
    description: Overproduction of gel-forming mucins generates the copious, often purulent sputum characteristic of bronchiectasis.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Mucus symptoms arise through goblet cell hyperplasia and metaplasia and
        reduced ciliary function through dyskinesia and loss of ciliated cells.
      explanation: >-
        The review directly links goblet-cell changes to mucus symptoms.
  - target: Chronic Cough
    description: Excess airway mucus stimulates the cough reflex, producing the productive chronic cough.
    evidence:
    - reference: DOI:10.1055/s-0041-1730891
      reference_title: Pathophysiology of Bronchiectasis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Mucus symptoms arise through goblet cell hyperplasia and metaplasia and
        reduced ciliary function through dyskinesia and loss of ciliated cells.
      explanation: >-
        The review supports mucus symptoms from goblet-cell changes; the cough
        reflex is a known but unmeasured intermediate.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: 'Pathophysiology of Bronchiectasis'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells.
    explanation: Direct support for goblet cell hyperplasia as a source of mucus symptoms in bronchiectasis.
  cell_types:
  - preferred_term: goblet cell
    term:
      id: CL:0000160
      label: goblet cell
  biological_processes:
  - preferred_term: mucus secretion
    term:
      id: GO:0070254
      label: mucus secretion
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
- name: Inflammasome Activation and IL-1beta Signaling
  description: NLRP3 inflammasome activation drives IL-1beta production, which directly impairs ciliary function, disrupts tight junctions, promotes mucus hyperconcentration, and is associated with severe disease and Proteobacteria enrichment.
  downstream:
  - target: Impaired Mucociliary Clearance
    description: >-
      Chronic IL-1beta exposure compromises epithelial cilia and tight-junction
      function, weakening mucociliary clearance.
    evidence:
    - reference: DOI:10.1183/13993003.01966-2023
      reference_title: Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells
      explanation: >-
        Airway epithelial-cell experiments directly support the causal edge
        from chronic IL-1beta signaling to impaired clearance.
  evidence:
  - reference: DOI:10.1183/13993003.01966-2023
    reference_title: 'Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.
    explanation: Cohort study (n=269) directly links airway IL-1beta to inflammasome activation, severity, and epithelial dysfunction.
  - reference: DOI:10.1183/13993003.01966-2023
    reference_title: 'Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis'
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells
    explanation: In vitro mechanistic evidence that IL-1beta directly impairs ciliary and tight-junction function in airway epithelial cells.
  biological_processes:
  - preferred_term: interleukin-1 beta production
    term:
      id: GO:0032611
      label: interleukin-1 beta production
  cellular_components:
  - preferred_term: NLRP3 inflammasome complex
    term:
      id: GO:0072559
      label: NLRP3 inflammasome complex
  cell_types:
  - preferred_term: airway epithelial cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
- name: Microbiome Dysbiosis
  description: Reduced microbial diversity with Proteobacteria dominance, particularly Pseudomonas aeruginosa and Haemophilus influenzae, drives chronic infection, exacerbations, and disease progression.
  downstream:
  - target: Recurrent Respiratory Infections
    description: Proteobacteria-dominant dysbiosis with persistent pathogen colonization drives chronic and recurrent airway infection.
  - target: Pulmonary Exacerbations
    description: >-
      Airway resistance-gene profiles and adverse resistotypes identify patients
      with more frequent exacerbations and poorer outcomes.
    evidence:
    - reference: DOI:10.1164/rccm.202306-1059oc
      reference_title: Airway “Resistotypes” and Clinical Outcomes in Bronchiectasis
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Proportional differences in baseline resistome profiles, including
        increased macrolide and multidrug resistance genes, associate with
        shorter intervals to the next exacerbation, whereas distinct resistome
        archetypes associate with frequent exacerbations, poorer lung function,
        geographic origin, and the host microbiome.
      explanation: >-
        Longitudinal human metagenomic data associate airway resistome states
        with time to and frequency of exacerbations.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: 'Pathophysiology of Bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes.
    explanation: Direct support for Proteobacteria dominance as a feature of severe disease.
  - reference: DOI:10.1186/s12931-024-02931-x
    reference_title: 'The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria
    explanation: Confirms reduced alpha diversity and Proteobacteria predominance via 16S rRNA sequencing of BAL samples.
  - reference: DOI:10.1183/16000617.0038-2024
    reference_title: Infection and the microbiome in bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bronchiectasis is marked by bronchial dilatation, recurrent infections and
      significant morbidity, underpinned by a complex interplay between
      microbial dysbiosis and immune dysregulation.
    explanation: >-
      This review directly supports microbiome–immune interplay as a central
      bronchiectasis mechanism.
  locations:
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
  - preferred_term: respiratory tract mucus
    term:
      id: UBERON:0000912
      label: mucus
genetic:
- name: CFTR
  gene_term:
    preferred_term: CFTR
    term:
      id: hgnc:1884
      label: CFTR
  association: Modifier gene
  notes: CFTR ion channel dysfunction contributes to airway surface liquid dehydration and mucus abnormalities in non-CF bronchiectasis, though the role is debated.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      These studies highlight that the role of CFTR in bronchiectasis remains
      contentious and that further multicenter studies on larger cohorts of
      patients are needed to resolve this debate.
    explanation: >-
      The review explicitly characterizes the human CFTR association as
      unresolved, so this is retained only as a proposed modifier.
- name: SCNN1A
  gene_term:
    preferred_term: SCNN1A
    term:
      id: hgnc:10599
      label: SCNN1A
  association: Susceptibility gene
  relationship_type: SUSCEPTIBILITY
  notes: >-
    ENaC (epithelial sodium channel) alpha subunit; hyperactivity causes airway
    surface dehydration and increased mucus viscosity, impairing mucociliary
    clearance. MONDO:0013087 "bronchiectasis with or without elevated sweat
    chloride 2" is the class for this gene's contribution and is recorded as a
    narrowMatch on this entry. Typed SUSCEPTIBILITY rather than CAUSATIVE: the
    cohort report attributes only a small fraction of patients to a Mendelian
    ENaC mechanism and rests the rest of its case on a case-control excess of
    rare polymorphisms.
  evidence:
  - reference: PMID:19462466
    reference_title: "Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In a small fraction of the patients, the disease could be potentially explained by an ENaC mutation by a Mendelian mechanism, such as p.V114I and p.F61L in SCNN1A."
    explanation: >-
      Names the two SCNN1A alleles the authors consider potentially Mendelian,
      and the hedging plus "small fraction" is why this record is typed
      SUSCEPTIBILITY.
  - reference: PMID:19462466
    reference_title: "Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Specifically, a significantly higher number of patients carried c.-55+5G>C or p.W493R in SCNN1A in the heterozygous state, with odds ratios (ORs) of 13.5 and 2.7, respectively."
    explanation: >-
      The case-control association for two heterozygous SCNN1A variants, which is
      a susceptibility observation rather than evidence of segregation.
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients who carry the p.W493R-SCNN1A, a variant that encodes for a
      hyperactive ENaC channel, have been identified as being at a higher risk
      of developing bronchiectasis.
    explanation: >-
      The review reports human susceptibility evidence for one SCNN1A variant;
      this does not establish broad causality for all SCNN1A variation.
- name: SCNN1G
  gene_term:
    preferred_term: SCNN1G
    term:
      id: hgnc:10602
      label: SCNN1G
  association: Susceptibility gene
  relationship_type: SUSCEPTIBILITY
  notes: >-
    ENaC gamma subunit. Two heterozygous amino-acid changes were found in
    patients with idiopathic bronchiectasis who carried no two CFTR coding
    mutations. MONDO:0013112 "bronchiectasis with or without elevated sweat
    chloride 3" is the class for this gene's contribution and is recorded as a
    narrowMatch on this entry. The same cohort's beta-subunit gene SCNN1B carried
    three of the five reported variants (p.Ser82Cys, p.Pro369Thr, p.Asn288Ser),
    and is deliberately not curated as a separate record: an OLS4 MONDO search
    for "SCNN1B" returns only MONDO:0020607 Liddle syndrome 1, and the three
    children of MONDO:0018956 idiopathic bronchiectasis are BESC1
    (MONDO:0008887, no causal gene asserted), BESC2 and BESC3, so the
    sweat-chloride series has no beta-subunit class to bind.
  evidence:
  - reference: PMID:18507830
    reference_title: "Could a defective epithelial sodium channel lead to bronchiectasis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sequencing of the exons and flanking introns of the ENaCbeta and gamma gene identified five different amino-acid changes"
    explanation: >-
      The variant discovery this record rests on, in a cohort selected for
      idiopathic bronchiectasis without two CFTR coding mutations.
  - reference: PMID:18507830
    reference_title: "Could a defective epithelial sodium channel lead to bronchiectasis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our results suggest that several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaCbeta/CFTR mutations or variants."
    explanation: >-
      The authors' conclusion, which is hedged and conditions the effect on a
      concurrent CFTR variant; this is the basis for the SUSCEPTIBILITY typing.
phenotypes:
- category: Constitutional
  name: Fatigue
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:42480819
    reference_title: 'Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bronchiectasis is a chronic respiratory condition involving a cycle of
      impaired mucociliary clearance, chronic infections, inflammation, and
      progressive airway destruction, leading to persistent cough with sputum
      production, dyspnea, and fatigue.
    explanation: >-
      The CHEST guideline explicitly includes fatigue among the clinical
      consequences of bronchiectasis.
- category: Respiratory
  name: Pulmonary Exacerbations
  notes: >-
    Acute worsening typically includes increased cough and sputum and worsened
    fatigue, and is associated with lung-function decline and lower quality of
    life.
  evidence:
  - reference: PMID:40293759
    reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Exacerbations of bronchiectasis, which typically present with increased
      cough and sputum and worsened fatigue, are associated with progressive
      decline in lung function and decreased quality of life.
    explanation: >-
      The review directly defines the exacerbation phenotype and its major
      clinical consequences.
- category: Respiratory
  name: Chronic Cough
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Chronic Cough
    term:
      id: HP:0034315
      label: Chronic cough
  evidence:
  - reference: DOI:10.1183/16000617.0179-2024
    reference_title: 'Neutrophilic inflammation in bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life.
    explanation: Chronic cough is a defining clinical feature of bronchiectasis.
- category: Respiratory
  name: Sputum Production
  frequency: VERY_FREQUENT
  notes: Often purulent and copious
  phenotype_term:
    preferred_term: Sputum Production
    term:
      id: HP:0033709
      label: Increased sputum production
  evidence:
  - reference: DOI:10.1183/16000617.0179-2024
    reference_title: 'Neutrophilic inflammation in bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life.
    explanation: Sputum production is a defining clinical feature of bronchiectasis.
- category: Respiratory
  name: Dyspnea
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:42480819
    reference_title: "Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bronchiectasis is a chronic respiratory condition involving a cycle of
      impaired mucociliary clearance, chronic infections, inflammation, and
      progressive airway destruction, leading to persistent cough with sputum
      production, dyspnea, and fatigue.
    explanation: >-
      The CHEST guideline identifies dyspnea among the clinical consequences of
      the bronchiectasis disease cycle.
- category: Respiratory
  name: Hemoptysis
  notes: Blood in cough due to airway damage
  phenotype_term:
    preferred_term: Hemoptysis
    term:
      id: HP:0002105
      label: Hemoptysis
  evidence:
  - reference: PMID:7555168
    reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Symptoms of bronchiectasis included chronic cough with the production of
      purulent sputum, hemoptysis, recurrent fever, and pleurisy.
    explanation: >-
      The 123-patient cohort directly documents hemoptysis as a bronchiectasis
      symptom; no frequency band is assigned because the abstract does not
      quantify it.
- category: Respiratory
  name: Recurrent Respiratory Infections
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Recurrent Respiratory Infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
  evidence:
  - reference: DOI:10.1183/16000617.0179-2024
    reference_title: 'Neutrophilic inflammation in bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life.
    explanation: Recurrent respiratory infections are a hallmark clinical feature of bronchiectasis.
- category: Respiratory
  name: Fixed Airflow Obstruction
  notes: Progressive airflow limitation that may develop in bronchiectasis patients, associated with Proteobacteria-enriched microbiome
  phenotype_term:
    preferred_term: Chronic pulmonary obstruction
    term:
      id: HP:0006510
      label: Chronic pulmonary obstruction
  evidence:
  - reference: DOI:10.1186/s12931-024-02931-x
    reference_title: 'The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations.
    explanation: Direct evidence that fixed airflow obstruction is a clinically relevant phenotype in bronchiectasis with worse outcomes.
- category: Respiratory
  name: Wheezing
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Wheezing
    term:
      id: HP:0030828
      label: Wheezing
  evidence:
  - reference: PMID:7555168
    reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The finding of crackles on chest examination was the rule (70%) with
      wheezing present in 34% of the group.
    explanation: >-
      Wheezing occurred in 34% of this 123-patient cohort, which falls in the
      FREQUENT (30-79%) band.
- category: Respiratory
  name: Crackles
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Crackles
    term:
      id: HP:0030830
      label: Crackles
  evidence:
  - reference: PMID:7555168
    reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The finding of crackles on chest examination was the rule (70%) with
      wheezing present in 34% of the group.
    explanation: >-
      Crackles occurred in 70% of this 123-patient cohort, which falls in the
      FREQUENT (30-79%) band.
biochemical:
- name: Bronchiectasis Biomarker Profiles
  presence: Variable
  context: >-
    Inflammatory, microbiome, radiologic, mucus, and epithelial measurements
    define heterogeneous profiles being investigated for prognosis and
    treatment selection; no single profile is universally diagnostic.
  evidence:
  - reference: DOI:10.1183/16000617.0234-2023
    reference_title: Biomarkers in bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Increasingly there are available methods to measure each of these
      components of the disease, revealing heterogeneous inflammatory profiles,
      microbiota, radiology and mucus and epithelial biology in patients with
      bronchiectasis.
    explanation: >-
      The biomarker review supports heterogeneous measurable disease profiles
      rather than a single universal biomarker.
- name: C-Reactive Protein (CRP)
  presence: Elevated
  context: >-
    Serum CRP can be elevated in infection-associated bronchiectasis,
    including Haemophilus influenzae-dominant disease; it is nonspecific.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      an increase in serum CRP
    explanation: >-
      The cited association supports elevated CRP in an infection-defined
      subgroup, not as a specific or universal bronchiectasis marker.
- name: Sputum Culture
  presence: Positive
  context: >-
    Identifies clinically actionable airway organisms, although conventional
    culture is insensitive and a negative result does not exclude infection.
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      sputum culture is a critical component
    explanation: >-
      The review directly supports sputum culture as an actionable assessment
      biomarker while noting its limited sensitivity.
- name: Neutrophil Elastase (NE)
  presence: Elevated
  context: High sputum NE activity associates with severe bronchiectasis, exacerbation risk, airway bacterial load, and disease progression; mechanistic biomarker of neutrophil-driven inflammation
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: 'Pathophysiology of Bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes.
    explanation: Supports elevated neutrophil elastase as a biomarker linked to worse outcomes in bronchiectasis.
- name: Interleukin-1 beta (IL-1beta)
  presence: Elevated
  context: Subset of patients with high airway IL-1beta show severe disease, mucus hyperconcentration, impaired ciliary function, and Proteobacteria-enriched microbiome
  evidence:
  - reference: DOI:10.1183/13993003.01966-2023
    reference_title: 'Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β.
    explanation: Cohort study links elevated airway IL-1beta to greater severity and amplified inflammatory response.
- name: Neutrophil Extracellular Traps (NETs)
  presence: Elevated
  context: NET complexes in sputum associate with higher disease severity, exacerbations, and mortality; include MPO, NE, resistin, and azurocidin
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our study found that NETs were present in sputum of patients with
      bronchiectasis and correlated with increasing severity, mortality, severe
      exacerbation, and a reduction in time to next exacerbation.
    explanation: >-
      The review reports multicohort sputum evidence linking NET abundance to
      severity, exacerbations, and mortality.
diagnosis:
- name: High-Resolution CT Scan
  description: >-
    Thin-section chest CT demonstrates permanent bronchial dilation and
    establishes the defining radiologic abnormality.
  diagnosis_term:
    preferred_term: computed tomography procedure
    term:
      id: NCIT:C17204
      label: Computed Tomography
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "AbstractBronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome."
    explanation: >-
      The review establishes permanent bronchial dilation on imaging as one of
      the two defining components of bronchiectasis.
- name: Pulmonary Function Test
  description: >-
    Pulmonary function testing characterizes airflow obstruction and supports
    severity assessment, but it does not establish the structural diagnosis.
    FEV1 as a percentage of predicted is the lung-function component of both
    multidimensional severity scores: the Bronchiectasis Severity Index (BSI)
    selected it as the most discriminatory lung-function measure for mortality
    and hospital admission, and the FACED score dichotomises it at a 50%
    cut-off for its F component.
  diagnosis_term:
    preferred_term: pulmonary function testing
    term:
      id: NCIT:C38081
      label: Pulmonary Function Test
  measurements:
  - preferred_term: FEV1 percent predicted
    term:
      id: LOINC:20152-5
      label: FEV1 measured/predicted
  reference_ranges:
  - loinc_term:
      id: LOINC:20152-5
      label: FEV1 measured/predicted
    unit: '%'
    population: FACED score derivation and validation cohorts, 2014 (non-cystic fibrosis bronchiectasis)
    notes: >-
      The abstract states the F component as "forced expiratory volume in 1 s %
      predicted (F, cut-off 50%, maximum value 2 points)" and does not say in
      its own text which side of the cut-off scores the points or on which side
      a value of exactly 50% falls; the bands partition the scale at the stated
      cut-off, and the lower stratum is flagged as the abnormal one because the
      score classifies severity by prognosis and the component's points are a
      severity contribution. Read the band names as the two F strata, not as a
      statement of the points each receives. The BSI derivation paper
      (PMID:24328736, full text cached without its tables) names FEV1 below 30%
      predicted as an independent predictor of hospital admission but its
      multi-stratum FEV1 point table is not in the cached prose, so no BSI bands
      are recorded.
    evidence:
    - reference: PMID:24232697
      reference_title: "Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: PRIMARY_RESULT
      snippet: "The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points)"
      explanation: States the FEV1 percent-predicted cut-off reproduced as the band boundary below and the maximum points the F component contributes.
    - reference: PMID:24232697
      reference_title: "Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: PRIMARY_RESULT
      snippet: "The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis."
      explanation: The score grades severity by prognosis, which is the basis on which the lower FEV1 stratum is flagged as the abnormal band.
    interpretation_bands:
    - name: FACED F component, FEV1 below the 50% cut-off
      upper_bound: 50.0
      unit: '%'
      abnormal_flag: LOW
      interpretation: >-
        Lower FEV1 stratum of the FACED F component; the component contributes
        up to 2 of the score's 7 points.
    - name: FACED F component, FEV1 at or above the 50% cut-off
      lower_bound: 50.0
      unit: '%'
      abnormal_flag: NORMAL
      interpretation: >-
        Upper FEV1 stratum of the FACED F component. NORMAL here means the
        component is not contributing to severity, not that the value sits in a
        population reference interval, which this row does not record.
  notes: >-
    Identity is bound at the method-less code for FEV1 as measured over
    predicted (LOINC:20152-5), the form both severity scores use; the FEV1
    volume and the FEV1/FVC ratio are not bound because neither score grades
    on them.
  evidence:
  - reference: PMID:24328736
    reference_title: "The bronchiectasis severity index. An international derivation and validation study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "Based on the Youden index, FEV1 % predicted was most discriminatory for mortality and hospital admissions and was used for subsequent analyses of lung function."
    explanation: The BSI derivation selected FEV1 percent predicted over the ratio and FVC as its lung-function measure, which is why that quantity is the measurement bound on this row.
  - reference: PMID:24328736
    reference_title: "The bronchiectasis severity index. An international derivation and validation study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: "Independent of this, Medical Research Council dyspnea score, FEV1 less than 30% predicted, and colonization with P. aeruginosa or other organisms were independent predictors of hospital admissions."
    explanation: The one FEV1 threshold the BSI paper states in its prose; recorded as evidence that FEV1 percent predicted carries a severity threshold in that score, with the full BSI point table left unbanded as the range notes explain.
  - reference: PMID:7555168
    reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pulmonary function studies documented airway obstruction to be present in
      54% of the lifetime nonsmokers.
    explanation: >-
      The cohort shows that pulmonary function testing identifies airflow
      obstruction in a substantial bronchiectasis subgroup.
treatments:
- name: Airway Clearance Techniques
  description: Physical therapies to enhance mucus clearance, such as chest physiotherapy.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
  evidence:
  - reference: PMID:41016738
    reference_title: "European Respiratory Society clinical practice guideline for the management of adult bronchiectasis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis, and pulmonary rehabilitation for those with impaired exercise capacity."
    explanation: The primary European Respiratory Society clinical practice guideline makes a strong recommendation in favour of airway clearance techniques for most patients with bronchiectasis.
- name: Pulmonary Rehabilitation
  description: >-
    Exercise-based pulmonary rehabilitation is recommended for patients with
    impaired exercise capacity.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
  evidence:
  - reference: PMID:41016738
    reference_title: European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The Task Force recommendations include strong recommendations in favour
      of airway clearance techniques for most patients with bronchiectasis, and
      pulmonary rehabilitation for those with impaired exercise capacity.
    explanation: >-
      The ERS guideline strongly recommends pulmonary rehabilitation for the
      exercise-limited subgroup.
- name: Antibiotic Treatment of Acute Exacerbations
  description: >-
    Antibiotics are used for acute bronchiectasis exacerbations, with agent,
    route, and duration selected from clinical severity and microbiology.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
  evidence:
  - reference: PMID:42480819
    reference_title: "Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Based on 47 studies, the panel developed 13 evidence-based
      recommendations addressing key management domains, including antibiotic
      treatment for acute exacerbations, duration and route of antibiotic
      therapy, long-term suppressive antibiotic and anti-inflammatory
      therapies, airway clearance strategies, management of hemoptysis and
      consideration of surgical resection in selected patients.
    explanation: >-
      The abstract establishes that the guideline addresses antibiotic
      treatment, route, and duration, but does not expose the direction or
      certainty of the individual recommendation.
    directness: INDIRECT
- name: Long-term Macrolide Therapy
  description: Maintenance macrolide antibiotics such as azithromycin or erythromycin reduce pulmonary exacerbations in selected patients, while requiring attention to macrolide resistance risk.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azithromycin
      term:
        id: CHEBI:2955
        label: azithromycin
    - preferred_term: erythromycin
      term:
        id: CHEBI:48923
        label: erythromycin
  evidence:
  - reference: PMID:22901887
    reference_title: 'Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year.
    explanation: EMBRACE was a randomized, double-blind, placebo-controlled trial supporting azithromycin for exacerbation prevention.
  - reference: PMID:23532242
    reference_title: 'Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Among patients with non-CF bronchiectasis, the 12-month use of erythromycin compared with placebo resulted in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance.
    explanation: BLESS supports long-term macrolide therapy reducing exacerbations while also documenting resistance risk.
- name: Long-Term Inhaled Antibiotic Therapy
  description: >-
    Long-term inhaled antibiotics are recommended for patients with chronic
    Pseudomonas aeruginosa infection who remain at high exacerbation risk.
  context: Chronic Pseudomonas aeruginosa infection with high exacerbation risk
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
  evidence:
  - reference: PMID:41016738
    reference_title: European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      We issue a strong recommendation for the use of long-term macrolide
      treatment for patients at high risk of exacerbations and a strong
      recommendation in favour of long-term inhaled antibiotics in patients
      with chronic Pseudomonas aeruginosa infection at high risk of
      exacerbation.
    explanation: >-
      The ERS guideline makes a strong recommendation for inhaled antibiotics
      in this defined high-risk subgroup.
- name: Pathogen Eradication Therapy
  description: >-
    Targeted eradication treatment may be used in selected circumstances after
    identifying a clinically important airway pathogen.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
  evidence:
  - reference: PMID:41016738
    reference_title: European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Conditional recommendations support the use of eradication treatment or
      mucoactive drugs in specific circumstances.
    explanation: >-
      The guideline conditionally supports eradication therapy but the abstract
      does not define every eligible pathogen or clinical circumstance.
- name: Mucoactive Therapy
  description: >-
    Nebulized saline and other mucoactive drugs may be used in selected patients
    to loosen tenacious secretions and support airway clearance.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: respiratory tract agent therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:40293759
    reference_title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
    supports: SUPPORT
    evidence_source: OTHER
    snippet: nebulization of saline to loosen tenacious secretions
    explanation: >-
      The clinical review explicitly includes nebulized saline for loosening
      tenacious bronchiectasis secretions.
  - reference: DOI:10.1183/13993003.01689-2023
    reference_title: 'Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Mucoactive drugs were also more likely to be used in participants with more severe disease.
    explanation: >-
      EMBARC documents real-world mucoactive-drug use, especially in more severe
      disease, but does not by itself establish comparative efficacy.
- name: Brensocatib
  description: Oral reversible dipeptidyl peptidase 1 inhibitor that reduces neutrophil serine protease activity and pulmonary exacerbations.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Brensocatib
      term:
        id: NCIT:C171778
        label: Brensocatib
  target_mechanisms:
  - target: Protease-Antiprotease Imbalance
    treatment_effect: INHIBITS
    description: Brensocatib inhibits DPP-1, targeting neutrophil serine proteases that drive the protease-antiprotease imbalance.
    evidence:
    - reference: PMID:40267423
      reference_title: 'Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation.
      explanation: The ASPEN trial abstract describes brensocatib's DPP-1 inhibition as targeting neutrophil serine proteases.
  evidence:
  - reference: PMID:40267423
    reference_title: 'Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among patients with bronchiectasis, once-daily treatment with brensocatib
      (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations
      than placebo, and the decline in FEV1 was less with the 25-mg dose of
      brensocatib than with placebo.
    explanation: >-
      ASPEN was a phase 3, double-blind trial demonstrating reduced pulmonary
      exacerbations with once-daily brensocatib.
- name: Surgery
  description: >-
    Surgical resection may be considered for selected patients after
    multidisciplinary assessment; it is not routine bronchiectasis treatment.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  evidence:
  - reference: PMID:42480819
    reference_title: "Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Based on 47 studies, the panel developed 13 evidence-based
      recommendations addressing key management domains, including antibiotic
      treatment for acute exacerbations, duration and route of antibiotic
      therapy, long-term suppressive antibiotic and anti-inflammatory
      therapies, airway clearance strategies, management of hemoptysis and
      consideration of surgical resection in selected patients.
    explanation: >-
      The abstract establishes that selected-patient resection is addressed,
      but does not expose the direction or certainty of the recommendation.
    directness: INDIRECT
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      removing damaging areas of the lung through surgery
    explanation: >-
      Names resection of damaged lung as one of the approaches directed at the
      consequences of structural lung damage, which is the rationale this
      treatment entry records.
- name: Bronchodilators for Airflow Obstruction
  description: >-
    Bronchodilators may be used to treat airflow obstruction as a consequence
    of structural lung disease; the review does not establish routine benefit
    for every patient with bronchiectasis.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: bronchodilator therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: bronchodilator
      term:
        id: NCIT:C319
        label: Bronchodilator
  evidence:
  - reference: DOI:10.1055/s-0041-1730891
    reference_title: Pathophysiology of Bronchiectasis
    supports: SUPPORT
    evidence_source: OTHER
    directness: INDIRECT
    snippet: >-
      Most approaches therefore aim to deal with the consequences of
      structural lung damage, such as treating air flow obstruction with
      bronchodilators
    explanation: >-
      Names bronchodilators as the treatment directed at airflow obstruction.
      The review states the therapeutic aim rather than a comparative result,
      so the support for using them in a given patient is inferential.
- name: Routine Inhaled Corticosteroids
  description: >-
    Inhaled corticosteroids should not be used routinely for bronchiectasis
    alone; separate indications such as severe asthma or allergic
    bronchopulmonary aspergillosis require individualized management.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: respiratory tract agent therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:41016738
    reference_title: European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
    supports: REFUTE
    evidence_source: OTHER
    snippet: >-
      We suggest not to routinely use long-term oral, non-macrolide antibiotic
      treatment or inhaled corticosteroids.
    explanation: >-
      The ERS guideline explicitly advises against routine inhaled
      corticosteroids in adults with bronchiectasis.
- name: Vaccinations
  description: Prevent respiratory infections and exacerbations.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: Vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
environmental:
- name: Pollution
  notes: >-
    Short-term sulfur-dioxide exposure was associated with emergency visits for
    bronchiectasis exacerbations in one retrospective study.
  exposure_term:
    preferred_term: Air pollution exposure
    term:
      id: ECTO:8000036
      label: exposure to air pollution
  evidence:
  - reference: PMID:29772571
    reference_title: Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The number of emergency room visits for exacerbation of bronchiectasis is
      associated with higher levels of SO2.
    explanation: >-
      This retrospective observational study supports an association between
      sulfur-dioxide exposure and bronchiectasis exacerbation visits.
- name: Smoking
  notes: >-
    In one clinical cohort, patients who had smoked showed greater airway
    obstruction than nonsmokers, while otherwise having a similar clinical
    picture.
  exposure_term:
    preferred_term: Tobacco smoking exposure
    term:
      id: ECTO:6000029
      label: exposure to tobacco smoking
  evidence:
  - reference: PMID:7555168
    reference_title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients who had smoked had much the same picture as nonsmokers, although
      they had a greater degree of airway obstruction.
    explanation: >-
      The cohort directly associates prior smoking with greater airway
      obstruction without implying broad causation of bronchiectasis.
  - reference: PMID:38888096
    reference_title: "The impact of smoking on bronchiectasis and its comorbidities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This review emphasizes the role of smoking in bronchiectasis development and exacerbation by compromising airways and immune function."
    explanation: Review of the clinical literature supporting smoking as a driver of bronchiectasis development and exacerbation.
notes: Bronchiectasis is characterized by a self-sustaining "vicious vortex" of mucociliary dysfunction, persistent infection with Proteobacteria-dominant dysbiosis (notably Pseudomonas aeruginosa), and chronic neutrophil-driven inflammation. Neutrophils release proteases (NE, PR3, CatG) and form NETs that degrade extracellular matrix, impair ciliary function, and damage epithelial barriers. Inflammasome activation with airway IL-1beta is associated with severe disease, mucus hyperconcentration, and epithelial dysfunction. The disease leads to irreversible bronchial dilation and progressive airflow limitation.
disease_term:
  preferred_term: bronchiectasis
  term:
    id: MONDO:0004822
    label: bronchiectasis
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0013087
      label: bronchiectasis with or without elevated sweat chloride 2
    mapping_predicate: skos:narrowMatch
    mapping_source: dismech
    mapping_justification: >
      The ENaC-subunit branch of this disease. MONDO:0013087 (BESC2) and
      MONDO:0013112 (BESC3) are grandchildren of this entry's MONDO:0004822
      anchor, through MONDO:0018956 idiopathic bronchiectasis, and their OWL
      axioms assert SCNN1A (hgnc:10599) and SCNN1G (hgnc:10602) respectively as
      causal genes. Both genes are curated on this entry as `genetic:` records
      wired to the Airway Surface Liquid Dehydration node. They are typed
      `SUSCEPTIBILITY` rather than `CAUSATIVE`, and no gene-defined
      `has_subtypes` row is created, because the primary reports describe
      heterozygous variants and case-control enrichment rather than Mendelian
      segregation of a clinically separable entity. The report behind
      MONDO:0013112 found five beta- and gamma-subunit amino-acid changes, two of
      them in SCNN1G, in the heterozygous state in 8 of its 55 patients, and
      concluded that they "might be deleterious", with the effect clearest in
      trans-heterozygotes who also carry a CFTR variant. The report behind
      MONDO:0013087 attributes only "a small fraction" of its cohort to a
      Mendelian mechanism and otherwise reports a more than three-fold excess of
      rare ENaC polymorphisms over controls. This is a considered disagreement with MONDO's `RO:0004003`
      typing, not an omission.
  - term:
      id: MONDO:0013112
      label: bronchiectasis with or without elevated sweat chloride 3
    mapping_predicate: skos:narrowMatch
    mapping_source: dismech
    mapping_justification: >
      The SCNN1G half of the same ENaC branch; see the justification on
      MONDO:0013087 above, which covers both terms.
classifications:
  harrisons_chapter:
  - classification_value: RESPIRATORY
references:
- reference: DOI:10.1055/s-0041-1730891
  title: Pathophysiology of Bronchiectasis
  findings: []
- reference: DOI:10.1164/rccm.202306-1059oc
  title: Airway “Resistotypes” and Clinical Outcomes in Bronchiectasis
  findings: []
- reference: DOI:10.1183/13993003.01689-2023
  title: 'Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)'
  findings: []
- reference: DOI:10.1183/13993003.01966-2023
  title: Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
  findings: []
- reference: DOI:10.1183/16000617.0038-2024
  title: Infection and the microbiome in bronchiectasis
  findings: []
- reference: DOI:10.1183/16000617.0055-2024
  title: Pathophysiology and genomics of bronchiectasis
  findings: []
- reference: DOI:10.1183/16000617.0179-2024
  title: Neutrophilic inflammation in bronchiectasis
  findings: []
- reference: DOI:10.1183/16000617.0234-2023
  title: Biomarkers in bronchiectasis
  findings: []
- reference: DOI:10.1186/s12931-024-02931-x
  title: 'The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study'
  findings: []
- reference: PMID:22901887
  title: 'Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.'
  findings: []
- reference: PMID:23532242
  title: 'Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial.'
  findings: []
- reference: PMID:29772571
  title: Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.
  findings: []
- reference: PMID:40293759
  title: 'Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.'
  findings: []
- reference: PMID:40267423
  title: Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.
  findings: []
- reference: PMID:41016738
  title: European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
  findings: []
- reference: PMID:42480819
  title: "Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline."
  findings: []
- reference: PMID:7555168
  title: Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
  findings: []
datasets:
- accession: geo:GSE217516
  title: Single-cell RNA-sequencing of bronchoalveolar lavage cells from humans with bronchiectasis
  description: Bronchiectasis is a lung disease characterized by irreversible dilation of the large airways (bronchodilatation), which often causes recurrent airway infection and non-resolving inflammation. In this study, we performed single-cell RNA-sequencing (scRNA-seq) to determine the heterogeneity of immune cells in the airways of bronchiectasis patients.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 6
  publication: PMID:41774079
  notes: Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE261102
  title: 'Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial'
  description: Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 7
  publication: PMID:39566467
  notes: Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE302095
  title: Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium
  description: 'Objectives: Examination of bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. Methods: We studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) was used to examine whether genes previously identified as increased or decreased in the bronchial epithelium of individuals with radiologic BE are significantly enriched among the genes most significantly altered in the nasal epithelium.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 132
  publication: PMID:42094231
  notes: Identified by GEO DataSets index search for Bronchiectasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS50000001808
  title: Integrated Single-Cell and Microbiome Profiling of Stable Bronchiectasis Across Disease Severity
  description: Bronchiectasis is a chronic respiratory disease characterized by persistent airway inflammation and recurrent infections. In this study, sputum samples from patients with mild, moderate, and severe bronchiectasis, collected during clinically stable disease, were analyzed using flow cytometry, single-cell RNA sequencing, and 16S rRNA gene sequencing. The resulting datasets enable characterization of neutrophil populations, transcriptional states, and airway microbial communities across disease severity stages.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Bronchiectasis"); description-level mentions were not accepted. EGA study_type: Transcriptome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: dbgap:phs000518
  title: 'NHLBI GO-ESP Family Studies: Idiopathic Bronchiectasis'
  description:  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied.
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Bronchiectasis"). Retrieved 2026-08-02.
- accession: dbgap:phs001279
  title: Cross-Sectional Characterization of Idiopathic Bronchiectasis
  description:  This GDMCC protocol will study adult patients with non-CF, idiopathic bronchiectasis, whose genetic etiologies are not known. Idiopathic bronchiectasis is reportedly more common in females with certain tall, thin body types and associated with environmental organisms, such as nontuberculous mycobacterium (NTM). The other susceptibility factors predisposing to bronchiectasis or acquisition of NTM are unclear. The study will attempt to broaden the understanding of this disease by comparing gender-associated factors and NTM status.
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Bronchiectasis"). Retrieved 2026-08-02.
📚

References & Deep Research

References

17
DOI:10.1055/s-0041-1730891
Pathophysiology of Bronchiectasis
No top-level findings curated for this source.
DOI:10.1164/rccm.202306-1059oc
Airway “Resistotypes” and Clinical Outcomes in Bronchiectasis
No top-level findings curated for this source.
DOI:10.1183/13993003.01689-2023
Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)
No top-level findings curated for this source.
DOI:10.1183/13993003.01966-2023
Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
No top-level findings curated for this source.
DOI:10.1183/16000617.0038-2024
Infection and the microbiome in bronchiectasis
No top-level findings curated for this source.
DOI:10.1183/16000617.0055-2024
Pathophysiology and genomics of bronchiectasis
No top-level findings curated for this source.
DOI:10.1183/16000617.0179-2024
Neutrophilic inflammation in bronchiectasis
No top-level findings curated for this source.
DOI:10.1183/16000617.0234-2023
Biomarkers in bronchiectasis
No top-level findings curated for this source.
DOI:10.1186/s12931-024-02931-x
The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study
No top-level findings curated for this source.
PMID:22901887
Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.
No top-level findings curated for this source.
PMID:23532242
Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial.
No top-level findings curated for this source.
PMID:29772571
Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.
No top-level findings curated for this source.
PMID:40293759
Non-Cystic Fibrosis Bronchiectasis in Adults: A Review.
No top-level findings curated for this source.
PMID:40267423
Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.
No top-level findings curated for this source.
PMID:41016738
European Respiratory Society clinical practice guideline for the management of adult bronchiectasis.
No top-level findings curated for this source.
PMID:42480819
Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline.
No top-level findings curated for this source.
PMID:7555168
Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort.
No top-level findings curated for this source.

Deep Research

2

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Disorder ▸

Disorder

  • Name: Bronchiectasis
  • Category: Respiratory Disease
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 9

Key Pathophysiology Nodes

  • Chronic Infection and Inflammation
  • Airway Dilation
  • Impaired Mucociliary Clearance
  • Neutrophil-Driven Inflammation
  • Protease-Antiprotease Imbalance
  • Goblet Cell Hyperplasia and Mucus Hypersecretion
  • Inflammasome Activation and IL-1beta Signaling
  • Microbiome Dysbiosis
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1055/s-0041-1730891
  • DOI:10.1164/rccm.202306-1059oc
  • DOI:10.1183/13993003.01689-2023
  • DOI:10.1183/13993003.01966-2023
  • DOI:10.1183/16000617.0038-2024
  • DOI:10.1183/16000617.0055-2024
  • DOI:10.1183/16000617.0179-2024
  • DOI:10.1183/16000617.0234-2023
  • DOI:10.1186/s12931-024-02931-x
Falcon ▸
Pathophysiology description (concise knowledge-base narrative)
Edison Scientific Literature 35 citations 2025-12-15T09:10:49.051530

Pathophysiology description (concise knowledge-base narrative) Non‑CF bronchiectasis arises from a self-sustaining “vicious vortex” of mucociliary dysfunction, persistent infection with Proteobacteria-dominant dysbiosis (notably Pseudomonas aeruginosa), and chronic neutrophil-driven inflammation that releases proteases and NETs, injuring the epithelium and altering mucus rheology, thereby worsening clearance and perpetuating infection. Inflammasome activation with airway IL‑1β links to higher severity, mucus hyperconcentration, epithelial barrier dysfunction, and Proteobacteria enrichment. Excess NSP activity (NE, PR3, CatG) over antiproteases is a causative axis, validated by clinical benefit of DPP‑1 inhibition that reduces airway protease activity and exacerbations. Clinically, frequent exacerbators and those with chronic P. aeruginosa have worse outcomes; airway clearance use remains suboptimal despite guideline recommendations (keir2021pathophysiologyofbronchiectasis pages 2-2, perea2024pathophysiologyandgenomics pages 2-3, aogain2024infectionandthe pages 1-2, johnson2024biomarkersinbronchiectasis pages 1-2, johnson2024biomarkersinbronchiectasis pages 3-4, aogain2024infectionandthe pages 6-7, chen2024theclinicalimpacts pages 1-2).

References

  1. (keir2021pathophysiologyofbronchiectasis pages 2-2): Holly R. Keir and James D. Chalmers. Pathophysiology of bronchiectasis. Seminars in Respiratory and Critical Care Medicine, 42:499-512, Jul 2021. URL: https://doi.org/10.1055/s-0041-1730891, doi:10.1055/s-0041-1730891. This article has 81 citations and is from a peer-reviewed journal.

  2. (keir2021pathophysiologyofbronchiectasis pages 1-2): Holly R. Keir and James D. Chalmers. Pathophysiology of bronchiectasis. Seminars in Respiratory and Critical Care Medicine, 42:499-512, Jul 2021. URL: https://doi.org/10.1055/s-0041-1730891, doi:10.1055/s-0041-1730891. This article has 81 citations and is from a peer-reviewed journal.

  3. (chalmers2025neutrophilicinflammationin pages 1-2): James D. Chalmers, Mark Metersky, Stefano Aliberti, Lucy Morgan, Sebastian Fucile, Melanie Lauterio, and Patrick P. McDonald. Neutrophilic inflammation in bronchiectasis. European Respiratory Review, 34:240179, Apr 2025. URL: https://doi.org/10.1183/16000617.0179-2024, doi:10.1183/16000617.0179-2024. This article has 20 citations and is from a peer-reviewed journal.

  4. (perea2024pathophysiologyandgenomics pages 2-3): Lidia Perea, Rosa Faner, James D. Chalmers, and Oriol Sibila. Pathophysiology and genomics of bronchiectasis. European Respiratory Review, 33:240055, Jul 2024. URL: https://doi.org/10.1183/16000617.0055-2024, doi:10.1183/16000617.0055-2024. This article has 29 citations and is from a peer-reviewed journal.

  5. (keir2021pathophysiologyofbronchiectasis pages 3-4): Holly R. Keir and James D. Chalmers. Pathophysiology of bronchiectasis. Seminars in Respiratory and Critical Care Medicine, 42:499-512, Jul 2021. URL: https://doi.org/10.1055/s-0041-1730891, doi:10.1055/s-0041-1730891. This article has 81 citations and is from a peer-reviewed journal.

  6. (keir2021pathophysiologyofbronchiectasis pages 2-3): Holly R. Keir and James D. Chalmers. Pathophysiology of bronchiectasis. Seminars in Respiratory and Critical Care Medicine, 42:499-512, Jul 2021. URL: https://doi.org/10.1055/s-0041-1730891, doi:10.1055/s-0041-1730891. This article has 81 citations and is from a peer-reviewed journal.

  7. (aogain2024infectionandthe pages 1-2): Micheál Mac Aogáin, Alison J. Dicker, Pontus Mertsch, and Sanjay H. Chotirmall. Infection and the microbiome in bronchiectasis. European Respiratory Review, 33:240038, Jul 2024. URL: https://doi.org/10.1183/16000617.0038-2024, doi:10.1183/16000617.0038-2024. This article has 24 citations and is from a peer-reviewed journal.

  8. (aogain2024infectionandthe pages 4-5): Micheál Mac Aogáin, Alison J. Dicker, Pontus Mertsch, and Sanjay H. Chotirmall. Infection and the microbiome in bronchiectasis. European Respiratory Review, 33:240038, Jul 2024. URL: https://doi.org/10.1183/16000617.0038-2024, doi:10.1183/16000617.0038-2024. This article has 24 citations and is from a peer-reviewed journal.

  9. (aogain2024infectionandthe pages 6-7): Micheál Mac Aogáin, Alison J. Dicker, Pontus Mertsch, and Sanjay H. Chotirmall. Infection and the microbiome in bronchiectasis. European Respiratory Review, 33:240038, Jul 2024. URL: https://doi.org/10.1183/16000617.0038-2024, doi:10.1183/16000617.0038-2024. This article has 24 citations and is from a peer-reviewed journal.

  10. (chen2024theclinicalimpacts pages 1-2): Yen-Fu Chen, Hsin-Han Hou, Ning Chien, Kai-Zen Lu, Chieh-Hua Lin, Yu-Chieh Liao, Kuo-Lung Lor, Jung-Yien Chien, Chung-Ming Chen, Chung-Yu Chen, Shih-Lung Cheng, Hao-Chien Wang, Po-Ren Hsueh, and Chong-Jen Yu. The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study. Respiratory Research, Aug 2024. URL: https://doi.org/10.1186/s12931-024-02931-x, doi:10.1186/s12931-024-02931-x. This article has 6 citations and is from a domain leading peer-reviewed journal.

  11. (johnson2024biomarkersinbronchiectasis pages 3-4): Emma D Johnson, Merete B. Long, and James D. Chalmers. Biomarkers in bronchiectasis. European Respiratory Review, 33:230234, Jul 2024. URL: https://doi.org/10.1183/16000617.0234-2023, doi:10.1183/16000617.0234-2023. This article has 17 citations and is from a peer-reviewed journal.

  12. (chalmers2025neutrophilicinflammationin pages 9-10): James D. Chalmers, Mark Metersky, Stefano Aliberti, Lucy Morgan, Sebastian Fucile, Melanie Lauterio, and Patrick P. McDonald. Neutrophilic inflammation in bronchiectasis. European Respiratory Review, 34:240179, Apr 2025. URL: https://doi.org/10.1183/16000617.0179-2024, doi:10.1183/16000617.0179-2024. This article has 20 citations and is from a peer-reviewed journal.

  13. (johnson2024biomarkersinbronchiectasis pages 1-2): Emma D Johnson, Merete B. Long, and James D. Chalmers. Biomarkers in bronchiectasis. European Respiratory Review, 33:230234, Jul 2024. URL: https://doi.org/10.1183/16000617.0234-2023, doi:10.1183/16000617.0234-2023. This article has 17 citations and is from a peer-reviewed journal.