Bird Fancier's Lung

Respiratory Disease MONDO:0005668 Pathograph 23 Show in embeddings browser Respiratory Disease Inflammatory Lung Disease

Bird fancier's lung is the avian-antigen form of hypersensitivity pneumonitis: an immune-mediated interstitial and small-airway lung disease caused by repeated inhalation of proteins from birds, feathers, or contaminated materials. It spans nonfibrotic inflammatory and fibrotic phenotypes; only a minority of exposed people develop disease.

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Classifications

Harrison's Part

🔗

Mappings

MONDO

MONDO:0005668 bird fancier's lung

MONDO:0005668 is the primary disease term for bird fancier's lung.

◆

Subtypes

Recurrent chronic bird fancier's lung

Historical chronic-BFL pattern with recurrent acute episodes followed by interstitial pulmonary fibrosis; retained as a bird-specific clinical course rather than as the primary modern classification.

Show evidence (1 reference)

PMID:12839317 SUPPORT Human Clinical

"One subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent BFL)"

The abstract defines a recurrent chronic BFL subtype marked by recurrent acute episodes and fibrotic progression.

Insidious chronic bird fancier's lung

Historical chronic-BFL pattern with slowly progressive respiratory disease and no recalled acute episodes; retained as a bird-specific clinical course rather than as the primary modern classification.

Show evidence (1 reference)

PMID:12839317 SUPPORT Human Clinical

"the other subgroup of patients has no history of acute episodes but has slowly progressive chronic respiratory disease (insidious BFL)."

The abstract defines an insidious subtype with slow progression and no acute episode history.

Discussions and Knowledge Gaps

How should positive bird-specific IgG or IgA be interpreted when other diagnostic domains are discordant?

INTERPRETATION OPEN interpretation_bfl_serology_exposure_not_causation

Attached to

diagnosis#Bird antigen-specific IgG serology as exposure support

Bird-specific antibodies document sensitization and likely exposure. They do not establish that the exposure caused the ILD, and test panels and thresholds are not standardized internationally. The entry therefore does not model positive serology as an independently diagnostic biomarker.

Show evidence (1 reference)

PMID:32706311 SUPPORT Other

"It was emphasized that a positive serum IgG result does not mean that the exposure is the cause of the lung condition; it only indicates that the patient has likely been exposed to a potential cause of HP at some point in his or her life"

The guideline directly separates exposure evidence from disease causation.

Which single-cell and profibrotic mechanisms demonstrated in pooled or non-avian HP are reproduced specifically in human avian-antigen disease?

HUMAN MODEL MISMATCH OPEN gap_bfl_antigen_stratified_fibrotic_mechanisms

Attached to

pathophysiology#Classical Monocyte Enrichment pathophysiology#MMP14-High Macrophage Profibrotic Activity

The single-cell cohorts are not stratified by inciting antigen, while the MMP14 perturbation study uses a non-avian SR-antigen mouse model. These results are retained as partial shared-HP evidence, not as established bird-specific mechanisms.

Show evidence (2 references)

PMID:38924775 SUPPORT Human Clinical

"Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States..."

The cohort is defined at HP phenotype level without an avian-antigen subgroup.

PMID:38218353 SUPPORT Model Organism

"We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag."

The perturbation is performed in an SR-antigen rather than avian-antigen model.

Do reported MUC5B and TOLLIP associations predict susceptibility or outcome specifically in bird-related HP rather than in pooled fibrotic HP?

KNOWLEDGE GAP OPEN gap_bfl_genetic_susceptibility_specificity

The available association is for fibrotic HP and is non-causal. MUC5B and TOLLIP are therefore not represented as causal BFL genes; antigen-stratified replication and functional evidence would be needed.

Show evidence (1 reference)

PMID:38309995 SUPPORT Human Clinical

"MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP."

The study reports association with pooled fibrotic HP, not causation or BFL specificity.

What is the comparative efficacy of nintedanib and pirfenidone in progressive fibrotic BFL after avian-antigen removal?

KNOWLEDGE GAP OPEN gap_bfl_antifibrotic_efficacy

Attached to

treatments#Nintedanib for Progressive Fibrosing Disease treatments#Investigational Pirfenidone for Fibrotic HP

INBUILD was not powered for the HP subgroup or stratified by avian exposure. The pirfenidone trial enrolled only 40 participants and was underpowered for its primary endpoint. BFL-specific comparative evidence remains absent.

Show evidence (2 references)

PMID:32145830 SUPPORT Human Clinical

"The INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups."

The trial authors explicitly limit diagnosis-specific inference.

PMID:37028940 SUPPORT Human Clinical

"The trial was underpowered to detect a difference in the primary end point."

The pirfenidone trial authors explicitly identify inadequate power.

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Pathophysiology

Exposure to Avian Proteins

Repeated inhalation of avian proteins from bird droppings, feathers, or serum triggers bird-related hypersensitivity pneumonitis.

lung UBERON:0002048

Downstream

Bird Antigen-Driven Humoral Response Repeated avian antigen exposure triggers measurable bird-specific antibody responses.

Th1/Th2 to Th2/Th17 Cytokine Shift Antigen exposure initiates the hypersensitivity-pneumonitis immune response that shifts across disease stages.

Inflammatory Alveolar and Interstitial Lung Injury Repeated avian antigen exposure initiates immune-mediated inflammation in the small airways, alveoli, and interstitium.

Show evidence (3 references)

DOI:10.3390/ijms24032884 SUPPORT Other

"Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins."

The review defines BRHP as an avian protein-induced interstitial lung disease.

PMID:39958101 SUPPORT Human Clinical

"Bird fancier's lung (BFL) is a subtype of hypersensitivity pneumonitis (HP), an immune-mediated interstitial lung disease (ILD) resulting from the repeated inhalation of avian proteins found in bird droppings, feathers, and serum."

The case report links BFL to repeated inhalation of avian proteins as the causative trigger for interstitial lung disease.

PMID:33318919 SUPPORT Human Clinical

"Bird Fancier's Lung is a type of hypersensitivity pneumonitis, an immunologically mediated lung disease due to repetitive exposure of air-borne avian antigen."

The report characterizes BFL as an immune-mediated interstitial lung disease driven by repetitive avian antigen exposure.

Expansion of Resident Monocytes and Interstitial Macrophages

Bird antigen exposure is associated with increased resident monocytes, interstitial macrophages, and type 2 dendritic cells in the lung.

monocyte CL:0000576 macrophage CL:0000235 dendritic cell CL:0000451

lung UBERON:0002048

Downstream

Th1/Th2 to Th2/Th17 Cytokine Shift Monocyte, macrophage, and dendritic-cell remodeling is modeled upstream of the stage-dependent T-cell cytokine shift.

Show evidence (1 reference)

DOI:10.3390/ijms24032884 SUPPORT Model Organism

"Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups."

The mouse model reports increased resident monocytes, interstitial macrophages, and type 2 dendritic cells after bird antigen exposure.

Reduction of Inflammatory Monocytes and Alveolar Macrophages

Bird antigen exposure is associated with reduced inflammatory monocytes, alveolar macrophages, and tolerogenic dendritic cells in the lung.

monocyte CL:0000576 macrophage CL:0000235 dendritic cell CL:0000451 alveolar macrophage CL:0000583

lung UBERON:0002048

Downstream

Th1/Th2 to Th2/Th17 Cytokine Shift Reduced inflammatory monocytes, alveolar macrophages, and tolerogenic dendritic cells are modeled as part of the myeloid-cell remodeling upstream of the stage-dependent cytokine shift.

Show evidence (1 reference)

DOI:10.3390/ijms24032884 SUPPORT Model Organism

The same experiment reports reduced inflammatory monocytes, alveolar macrophages, and tolerogenic dendritic cells.

Th1/Th2 to Th2/Th17 Cytokine Shift

Early disease shows a mixed Th1/Th2 response, while progression shifts toward a Th2/Th17 mixed response.

T cell CL:0000084

T cell activation GO:0042110

lung UBERON:0002048

Downstream

Inflammatory Alveolar and Interstitial Lung Injury The stage-dependent T-cell cytokine program participates in the inflammatory lung response measured in the pigeon-serum model.

Show evidence (1 reference)

DOI:10.3390/ijms24032884 SUPPORT Model Organism

"In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response."

The cytokine profile indicates a stage-dependent shift toward Th2/Th17 responses during disease progression.

Inflammatory Alveolar and Interstitial Lung Injury

Avian-antigen-driven immune responses produce mononuclear alveolitis and interstitial/small-airway inflammation, impairing gas exchange and causing acute and chronic respiratory symptoms.

mononuclear cell CL:0000842

inflammatory response GO:0006954 ↑ INCREASED

alveolus of lung UBERON:0002299 lung connective tissue UBERON:0000114

Downstream

Dyspnea Active interstitial and alveolar inflammation produces breathlessness.

Cough Small-airway and interstitial inflammation produces cough.

Fever Acute inflammatory episodes can produce fever.

Fatigue Chronic inflammatory HP can produce systemic fatigue.

Hypoxemia Alveolar and interstitial injury can impair pulmonary gas exchange.

Pulmonary Fibrosis Persistent inflammatory injury can progress to fibrotic remodeling.

Show evidence (2 references)

PMID:14503346 SUPPORT Human Clinical

"a transbronchial lung biopsy (TBLB) specimen showed alveolitis due to the infiltration of mononuclear cells."

A human feather-associated BFL case directly documents mononuclear alveolitis.

PMID:39958101 SUPPORT Human Clinical

The clinical report identifies the interstitial inflammatory compartment in human BFL.

Bird Antigen-Driven Humoral Response

Bird antigen exposure triggers B cell activation and elevated serum IgG/IgA to avian proteins in bird-related hypersensitivity pneumonitis.

B cell CL:0000236

B cell activation GO:0042113 antigen processing and presentation GO:0019882

lung UBERON:0002048

Downstream

Inflammatory Alveolar and Interstitial Lung Injury Antigen-specific humoral responses participate with T-cell responses in lymphocytic and granulomatous lung inflammation.

Show evidence (1 reference)

PMID:33041192 SUPPORT Human Clinical

"The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects."

Elevated bird-specific IgG/IgA in affected patients supports a humoral immune response to avian antigens.

Classical Monocyte Enrichment

Fibrotic-HP cohorts not stratified by inciting antigen show elevated classical monocytes enriched for CCL3hi/CCL4hi and S100Ahi states. This is shared fibrotic-HP evidence, not a bird-specific result.

monocyte CL:0000576

chemokine-mediated signaling pathway GO:0070098

lung UBERON:0002048

Downstream

Monocyte-to-SPP1hi Macrophage Differentiation Enriched classical monocyte states feed the profibrotic macrophage differentiation trajectory.

Show evidence (1 reference)

PMID:38924775 SUPPORT Human Clinical

"Compared with control samples, FHP has elevated classical monocytes (adjusted-P = 2.5 × 10-3) and is enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-P < 2.2 × 10-16)."

Single-cell profiling identifies enriched states in fibrotic HP without avian-antigen stratification.

Monocyte-to-SPP1hi Macrophage Differentiation

In non-antigen-stratified fibrotic HP, S100Ahi classical monocytes differentiate toward SPP1hi lung macrophages associated with fibrosis; the branch is extrapolated to fibrotic BFL.

monocyte CL:0000576 macrophage CL:0000235

lung UBERON:0002048

Downstream

Pulmonary Fibrosis SPP1-high lung macrophages are associated with the fibrotic remodeling phenotype in fibrotic hypersensitivity pneumonitis.

Show evidence (1 reference)

PMID:38924775 SUPPORT Human Clinical

"Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis."

Trajectory analyses link classical monocytes to profibrotic macrophages in general fibrotic HP.

Cytotoxic T Cell Program with Profibrotic Signaling

Non-antigen-stratified fibrotic HP features GZMhi cytotoxic T cells with transcriptional programs implicating TGFβ, TNFα, and NFκB pathways; this branch is shared-context evidence for fibrotic BFL.

T cell CL:0000084

T cell activation GO:0042110

lung UBERON:0002048

Downstream

Pulmonary Fibrosis Cytotoxic T cells with TGF-beta, TNF-alpha, and NF-kappaB programs are modeled as part of the profibrotic inflammatory branch.

Show evidence (1 reference)

PMID:38924775 SUPPORT Human Clinical

"Compared with both control subjects and IPF, cells from patients with FHP are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit TF activities indicative of TGFβ and TNFα and NFκB pathways."

Cytotoxic T cell enrichment with profibrotic signaling programs supports a T cell-driven inflammatory mechanism.

MMP14-High Macrophage Profibrotic Activity

In a non-avian Saccharopolyspora rectivirgula-antigen HP model, MMP14-high M2-like macrophages promote fibroblast-to-myofibroblast transition. This informs a shared HP-fibrosis mechanism but is an extrapolation to BFL.

alveolar macrophage CL:0000583

extracellular matrix organization GO:0030198

alveolus of lung UBERON:0002299

Downstream

Pulmonary Fibrosis MMP14-high macrophage promotion of fibroblast-to-myofibroblast transition contributes to pulmonary fibrosis.

Show evidence (1 reference)

PMID:38218353 SUPPORT Model Organism

"we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT)."

The non-avian HP model identifies a macrophage subset driving fibroblast-to-myofibroblast transition.

TLR2 and NF-κB Regulation of MMP14 and Exosome Secretion

In the non-avian SR-antigen HP model, TLR2 and NF-κB signaling regulate macrophage MMP14 expression and exosome secretion; applicability to BFL is not yet directly established.

macrophage CL:0000235

Downstream

MMP14-High Macrophage Profibrotic Activity TLR2 and NF-kappaB signaling regulate the MMP14-high macrophage profibrotic program.

Show evidence (1 reference)

PMID:38218353 SUPPORT Model Organism

"We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag."

The abstract links TLR2/NF-κB signaling to MMP14 regulation and exosome secretion in HP macrophages.

✶

Histopathology

Alveolitis with Mononuclear Infiltration

Transbronchial lung biopsy may show alveolitis due to mononuclear cell infiltration.

Show evidence (1 reference)

PMID:14503346 SUPPORT Human Clinical

"a transbronchial lung biopsy (TBLB) specimen showed alveolitis due to the infiltration of mononuclear cells."

The case report documents biopsy-confirmed alveolitis in bird fancier's lung.

Bronchiolocentric Interstitial Pneumonia with Granulomatous Inflammation

Typical nonfibrotic HP histology combines bronchiolocentric cellular interstitial pneumonia, chronic bronchiolitis, and poorly formed nonnecrotizing granulomatous inflammation. These findings support BFL only when integrated with avian exposure and the other diagnostic domains.

Show evidence (1 reference)

PMID:32706311 SUPPORT Other

"A confident histopathological diagnosis of nonfibrotic HP requires the presence of typical histopathological features. These include 1) a cellular interstitial pneumonia accentuated around small airways (“bronchiolocentric”) accompanied by 2) a cellular chronic bronchiolitis, 3) a distinctive..."

The official guideline defines the characteristic nonfibrotic-HP histologic triad.

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

Metabolism 1

Fever HP:0001945

Show evidence (1 reference)

PMID:14503346 SUPPORT Human Clinical

"A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."

The case report documents low-grade fever in bird fancier's lung.

Respiratory 4

Dyspnea FREQUENT HP:0002094

Show evidence (3 references)

PMID:14503346 SUPPORT Human Clinical

"A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."

The case report documents shortness of breath in bird fancier's lung.

PMID:39958101 SUPPORT Human Clinical

"We present the case of a 43-year-old male pigeon keeper with an eight-week history of progressive dyspnea on exertion and intermittent chest pain."

The case report describes progressive dyspnea on exertion in BFL.

PMID:32706311 SUPPORT Other

"Common symptoms and signs of both nonfibrotic and fibrotic HP include dyspnea, cough, and midinspiratory squeaks (or chirping rales or squawks) (32)."

The guideline's qualitative term "Common" maps to FREQUENT under the DisMech frequency-evidence SOP. Because the source covers HP broadly rather than an avian-antigen subgroup, it is retained as PARTIAL support for the BFL frequency band.

Cough FREQUENT HP:0012735

Show evidence (2 references)

PMID:14503346 SUPPORT Human Clinical

"A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."

The case report describes cough in bird fancier's lung.

PMID:32706311 SUPPORT Other

"Common symptoms and signs of both nonfibrotic and fibrotic HP include dyspnea, cough, and midinspiratory squeaks (or chirping rales or squawks) (32)."

Pulmonary Fibrosis HP:0002206

Show evidence (4 references)

PMID:37028940 SUPPORT Human Clinical

"Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality."

The trial focuses on fibrotic hypersensitivity pneumonitis, supporting pulmonary fibrosis as a clinical phenotype.

PMID:32145830 SUPPORT Human Clinical

"the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis"

The INBUILD subgroup analysis includes hypersensitivity pneumonitis within progressive fibrosing ILD populations, supporting a fibrotic phenotype.

PMID:24480143 SUPPORT Human Clinical

"In the 3 diseases, most important prognosis-predicting factor is the extent of fibrotic score (the extent of honeycombing and reticulation) calculated on high-resolution computed tomography scans or fibrosis estimated on chest radiographs."

Chronic HP is discussed alongside fibrotic scoring on HRCT, reinforcing pulmonary fibrosis as a key disease feature.

+ 1 more reference

Hypoxemia HP:0012418

Show evidence (1 reference)

PMID:11131880 SUPPORT Human Clinical

"A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure."

The case demonstrates hypoxia as part of acute bird hypersensitivity pneumonitis.

Constitutional 1

Fatigue HP:0012378

Show evidence (1 reference)

PMID:6761066 SUPPORT Other

"Chronically, these diseases may present with the gradual onset of cough, dyspnea on exertion, fatigue, anorexia, and weight loss which may progress to pulmonary fibrosis or severe pulmonary insufficiency."

The clinical review describes fatigue among chronic hypersensitivity pneumonitis presentations.

🗃️

External Assertions

ATS/JRS/ALAT adult hypersensitivity pneumonitis diagnostic guideline

ATS/JRS/ALAT clinical practice guideline PMID:32706311

The official adult HP guideline supplies the nonfibrotic/fibrotic classification and multidisciplinary diagnostic framework applied to this avian-antigen subtype.

Show evidence (1 reference)

PMID:32706311 SUPPORT Other

"HP was classified into nonfibrotic and fibrotic phenotypes."

The official guideline establishes the current phenotype-based classification.

German S2k hypersensitivity pneumonitis diagnosis and treatment guideline

German Respiratory Society and German Society for Allergology and Clinical Immunology clinical practice guideline PMID:39870058

The 2025 S2k guideline adds treatment recommendations and distinguishes inflammatory and fibrotic patterns across acute and chronic HP courses.

Show evidence (1 reference)

PMID:39870058 SUPPORT Other

"Particular emphasis was placed on the different clinical courses (acute and chronic) and their characteristics (inflammatory and/or fibrotic pattern), which present differential diagnostic challenges and ultimately result in different treatment approaches."

The guideline explicitly links phenotype and clinical course to treatment strategy.

💊

Medical Actions

Identification and Avoidance of Avian Antigen

Category: Therapeutic Action: supportive care Ontology label: Supportive Care NCIT:C15747

Identify and remove the inciting avian source. Depending on the exposure, this can require removing birds, avoiding feather/down products, remediating contaminated material, and preventing indirect occupational or household exposure. Benefit is clearest in nonfibrotic HP; established fibrosis may continue to progress.

Mechanism Target:

INHIBITS Exposure to Avian Proteins

Show evidence (1 reference)

PMID:32764620 SUPPORT Other

"Complete antigen avoidance is the mainstay of treatment."

Removal of the inciting antigen directly interrupts the initiating exposure.

Target Phenotypes: Dyspnea HP:0002094 Cough HP:0012735

Show evidence (3 references)

PMID:32764620 SUPPORT Other

"Complete antigen avoidance is the mainstay of treatment."

The review identifies complete antigen avoidance as first-line management.

DOI:10.3390/jcm8010014 SUPPORT Human Clinical

"FVC% and DLCO% increased in nfHP patients after exposure avoidance, while a positive numerical trend was seen for FVC% after exposure avoidance in fHP patients (p = 0.15)."

Retrospective data support lung-function improvement in nonfibrotic HP but leave benefit in fibrotic HP uncertain.

DOI:10.1371/journal.pone.0273544 SUPPORT Human Clinical

"In our retrospective cohort, 136 patients met high or definite probability of HP and were included in the analysis. Median transplant-free survival was better in patients with antigen identified on clinical history alone than patients without identified antigen. Feather exposure was associated..."

The cohort supports systematic identification of live-bird and feather exposures but does not directly test avoidance.

Systemic Corticosteroids for Inflammatory Disease

Category: Therapeutic Action: corticosteroid agent therapy Ontology label: Systemic Corticosteroid Therapy NCIT:C122080

Agent: prednisone CHEBI:8382

Systemic glucocorticoids such as prednisone are used for clinically significant inflammatory/nonfibrotic HP. Observational evidence does not establish a survival benefit, and the same cohort found no therapeutic effect in fibrotic HP.

Mechanism Target:

INHIBITS Inflammatory Alveolar and Interstitial Lung Injury

Show evidence (1 reference)

DOI:10.3390/jcm8010014 SUPPORT Human Clinical

"Although nfHP patients showed FVC% and DLCO% increase after corticosteroid initiation, no therapeutic effect was seen in fHP patients."

Phenotype-stratified observational data support an anti-inflammatory benefit only in nonfibrotic HP.

Target Phenotypes: Dyspnea HP:0002094 Cough HP:0012735

Show evidence (2 references)

DOI:10.3390/jcm8010014 SUPPORT Human Clinical

"Although nfHP patients showed FVC% and DLCO% increase after corticosteroid initiation, no therapeutic effect was seen in fHP patients."

The retrospective cohort supports phenotype-specific benefit and limits extrapolation to fibrosis.

PMID:39958101 SUPPORT Human Clinical

"The patient was diagnosed with BFL and treated with a tapering regimen of oral corticosteroids, starting at 40 mg/day."

A single BFL case documents corticosteroid use but cannot establish comparative efficacy.

Mycophenolate Mofetil or Azathioprine as Steroid-Sparing Therapy

Category: Therapeutic Action: immunosuppressive therapy Ontology label: Immunosuppressive Therapy NCIT:C15261

Agent: mycophenolate mofetil CHEBI:8764 azathioprine CHEBI:2948

Mycophenolate mofetil or azathioprine may be used as steroid-sparing immunosuppression in chronic HP. Retrospective data found improved DLCO but no significant FVC improvement; prospective validation is lacking.

Mechanism Target:

INHIBITS Inflammatory Alveolar and Interstitial Lung Injury

Show evidence (1 reference)

PMID:27816444 SUPPORT Human Clinical

"Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P < .001) after 1 year of treatment."

Observational lung-function data support a possible steroid-sparing effect without FVC improvement.

Target Phenotypes: Dyspnea HP:0002094

Show evidence (1 reference)

PMID:27816444 SUPPORT Human Clinical

The retrospective study reports the limited lung-function outcome and calls for prospective trials.

Nintedanib for Progressive Fibrosing Disease

Category: Therapeutic Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352

Agent: nintedanib CHEBI:85164

Nintedanib reduces FVC decline across progressive fibrosing ILDs. The INBUILD analysis included chronic HP, but it was not powered to prove benefit within the HP subgroup and did not stratify bird-related disease.

Target Phenotypes: Pulmonary fibrosis HP:0002206

Show evidence (1 reference)

PMID:32145830 SUPPORT Human Clinical

"The INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups. However, its results suggest that nintedanib reduces the rate of ILD progression, as measured by FVC decline, in patients who have a chronic fibrosing ILD and..."

The randomized trial supports the broader progressive-fibrosing-ILD indication while preserving subgroup uncertainty.

Investigational Pirfenidone for Fibrotic HP

Category: Therapeutic Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352

Agent: pirfenidone CHEBI:32016

A small randomized trial in progressive fibrotic HP was interrupted by the COVID-19 pandemic and underpowered for its primary FVC endpoint. Pirfenidone improved a secondary progression-free-survival endpoint but remains investigational for this indication.

Target Phenotypes: Pulmonary fibrosis HP:0002206

Show evidence (2 references)

PMID:37028940 SUPPORT Human Clinical

"The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP."

The published trial reports a favorable secondary endpoint while explicitly acknowledging inadequate power for the primary endpoint.

clinicaltrials:NCT02958917 SUPPORT Human Clinical

"The use of pirfenidone has not been approved for the treatment of FHP. It is considered experimental treatment in this study."

The trial registry explicitly identifies pirfenidone as experimental for fibrotic HP.

🌍

Environmental Factors

Bird Antigen Exposure

Exposure to bird proteins from bird breeding, feather products, or fertilizer with fowl droppings.

Show evidence (6 references)

PMID:33041192 SUPPORT Human Clinical

"Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings."

The abstract explicitly lists common avian antigen exposure sources.

PMID:14503346 SUPPORT Human Clinical

"She had raised two budgerigars for the last 15 years and had been using a feather duvet for one year."

The case report documents direct bird exposure and feather product exposure associated with bird fancier's lung.

PMID:1053441 SUPPORT Human Clinical

"Among fifty-three Salt Lake City, Utah area pigeon fanciers, 21% were found to have the clinical picture of pigeon breeders' disease."

Pigeon fancier exposure is directly tied to bird fancier's lung in this prevalence study.

+ 3 more references

Mechanism Target:

TRIGGERS Exposure to Avian Proteins — Keeping birds, or using feather products, delivers avian protein to the airway repeatedly over months to years, and it is the repetition rather than any single exposure that produces disease.

Show evidence (1 reference)

PMID:39958101 SUPPORT Human Clinical

"immune-mediated interstitial lung disease (ILD) resulting from the repeated inhalation of avian proteins found in bird droppings, feathers, and serum."

Defines the disease as resulting from repeated inhalation of avian proteins found in bird droppings, feathers and serum, the exposure this node represents.

🔬

Biochemical Markers

Bird antigen-specific IgG/IgA antibodies (Positive)

Show evidence (3 references)

PMID:33041192 SUPPORT Human Clinical

Elevated bird-specific antibodies are reported in affected patients.

PMID:38762468 SUPPORT Human Clinical

"Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP."

The study uses serial bird-specific IgG testing against pigeon serum in fibrotic avian HP.

PMID:40049235 SUPPORT Human Clinical

"The mean titers of anti-pigeon IgG antibody by ELISA were 0.659 ± 0.381 and 0.494 ± 0.187 in the bird-related fibrotic HP and control groups, respectively (p = 0.012)."

Anti-pigeon IgG titers are higher in bird-related fibrotic HP, supporting serologic evidence for avian antigen exposure.

🔬

Diagnosis

Multidisciplinary diagnostic integration

BFL is diagnosed by integrating avian exposure assessment, thoracic HRCT, BAL cellular analysis, and—when needed—histopathology in multidisciplinary discussion. No single feature is sufficient in isolation.

diagnostic procedure NCIT:C18020

Show evidence (2 references)

PMID:33861992 SUPPORT Other

"Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy."

The CHEST guideline defines the multidisciplinary sequence used for suspected avian HP.

PMID:32706311 SUPPORT Other

"Although the diagnosis of HP is predominantly based on exposure identification, chest HRCT scan pattern, and bronchoscopic/histopathological findings, a major challenge is that no individual feature is sufficient in isolation, nor are any mandatory."

The official guideline cautions against treating any one diagnostic domain as definitive.

Avian and occupational exposure history

A structured history should assess live birds, droppings, feathers or down bedding, contaminated fertilizer, occupational sources, and indirect household exposure.

diagnostic procedure NCIT:C18020

Show evidence (2 references)

PMID:32706311 SUPPORT Other

"Pending the availability of a validated questionnaire, the guideline committee advocates that clinicians take a thorough history to identify potential exposures and sources in the patient’s environment that are known to be associated with HP."

The guideline prioritizes systematic exposure history.

PMID:39958101 SUPPORT Human Clinical

"A thorough occupational history uncovered significant avian antigen exposure, and a family history suggested genetic susceptibility."

A BFL case illustrates how detailed history establishes avian exposure.

High-resolution computed tomography pattern

Nonfibrotic BFL commonly shows ill-defined centrilobular nodules, ground-glass opacity, mosaic attenuation, and air trapping; fibrotic disease adds reticulation, traction bronchiectasis, or honeycombing.

diagnostic procedure NCIT:C18020

Show evidence (2 references)

PMID:24480143 SUPPORT Human Clinical

"In chronic HP, the presence of lobular areas of decreased attenuation and centrilobular small nodules and the absence of lower lung zone predominance are characteristically observed."

The HRCT pattern distinguishes chronic HP from other fibrotic ILDs.

PMID:39958101 SUPPORT Human Clinical

"HRCT revealed bilateral diffuse centrilobular nodules, patchy ground-glass opacities, and a mosaic attenuation pattern without fibrosis, consistent with acute HP."

The case report highlights characteristic HRCT findings in BFL.

Bronchoalveolar lavage lymphocyte cellular analysis

BAL lymphocytosis supports HP in the appropriate exposure and imaging context, particularly nonfibrotic disease, but is not a stand-alone BFL diagnosis.

diagnostic procedure NCIT:C18020

Show evidence (2 references)

PMID:14503346 SUPPORT Human Clinical

"Bronchoalveolar lavage (BAL) revealed a marked increase in lymphocytes"

The case report documents BAL lymphocytosis in feather-associated BFL.

PMID:32706311 SUPPORT Other

"recommends obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis (recommendation, very low confidence in the estimated effects)."

The guideline recommends BAL lymphocyte analysis for suspected nonfibrotic HP while grading the evidence as very low confidence.

Bird antigen-specific IgG serology as exposure support

Elevated bird-specific IgG can support prior exposure and sensitization, but it neither proves that birds caused the lung disease nor independently confirms or excludes BFL. IgA testing has been studied but is not part of the standard guideline formulation.

diagnostic procedure NCIT:C18020

Show evidence (4 references)

PMID:33041192 SUPPORT Human Clinical

The bird-specific study shows group-level discrimination, supporting exposure attribution rather than stand-alone diagnosis.

PMID:38762468 SUPPORT Human Clinical

"Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP."

Serial testing demonstrates an exposure biomarker in fibrotic avian HP.

PMID:40049235 SUPPORT Human Clinical

"The mean titers of anti-pigeon IgG antibody by ELISA were 0.659 ± 0.381 and 0.494 ± 0.187 in the bird-related fibrotic HP and control groups, respectively (p = 0.012)."

Elevated anti-pigeon IgG supports avian sensitization in the correct clinical context.

+ 1 more reference

Inhalation challenge test

Specific avian inhalation challenge can help identify the inciting exposure in centers with appropriate expertise; it is a specialized component of exposure assessment, not a routine stand-alone test.

diagnostic procedure NCIT:C18020

Show evidence (2 references)

PMID:35779842 SUPPORT Human Clinical

"The inhalation challenge test for bird-related fibrotic HP was more sensitive than the anti-bird IgG antibodies."

The comparative study supports challenge testing as a specialized exposure-attribution tool.

PMID:32706311 SUPPORT Other

"Exposure assessment includes a thorough clinical history and/or serum IgG testing against potential antigens associated with HP and/or, in centers with the appropriate expertise and experience, specific inhalational challenge testing"

The guideline restricts specific inhalational challenge to experienced centers.

📈

Progression

Acute inflammatory presentation

An acute presentation can begin within hours after a high avian-antigen exposure and commonly aligns with a nonfibrotic inflammatory phenotype.

Show evidence (1 reference)

PMID:6761066 SUPPORT Other

"Symptoms usually begin 4 to 6 hr after exposure to large quantities of causative organic dust."

The review describes rapid onset after exposure in acute disease.

Chronic fibrotic presentation

Chronic disease can begin gradually and develop pulmonary fibrosis; the current fibrotic/nonfibrotic phenotype should be recorded separately from the time course.

Show evidence (1 reference)

PMID:6761066 SUPPORT Other

The review notes gradual onset and progression to fibrosis.

Progressive fibrotic disease

Once a progressive fibrotic phenotype is established, decline may continue despite removal of the identified exposure.

Show evidence (1 reference)

PMID:32764620 SUPPORT Other

"Some patients with fibrotic HP may evolve to a progressive phenotype, even with complete exposure avoidance."

The review establishes that exposure removal does not invariably halt fibrotic progression.

🌍

Epidemiology

Salt Lake City pigeon-fancier cohort

A selected regional cohort found clinical pigeon breeders' disease in 21% of 53 pigeon fanciers; this exposure-cohort proportion is not a general population prevalence estimate.

Show evidence (1 reference)

PMID:1053441 SUPPORT Human Clinical

"Among fifty-three Salt Lake City, Utah area pigeon fanciers, 21% were found to have the clinical picture of pigeon breeders' disease."

The study supplies a cohort-specific proportion among heavily exposed pigeon fanciers.

Common form of hypersensitivity pneumonitis

Bird fancier's lung is a common form of hypersensitivity pneumonitis among exposed populations.

Show evidence (1 reference)

PMID:21870048 SUPPORT Other

"Bird fancier's lung (BFL) resulting from avian antigen exposure is a very common form of hypersensitivity pneumonitis."

The review describes BFL as a very common form of HP.

🔀

Differential Diagnoses

Conditions with similar clinical presentations that must be differentiated from Bird Fancier's Lung:

Idiopathic Pulmonary Fibrosis MONDO:0800504

Overlapping Features Idiopathic pulmonary fibrosis can mimic chronic hypersensitivity pneumonitis with dyspnea and fibrosis, but has distinct HRCT distribution and feature patterns.

Distinguishing Features

Honeycombing with lower lung zone predominance on HRCT
Absence of centrilobular small nodules

Show evidence (1 reference)

PMID:24480143 SUPPORT Human Clinical

"In idiopathic pulmonary fibrosis or usual interstitial pneumonia, however, the presence of honeycombing with lower lung zone predominance and the absence of centrilobular small nodules are important findings that allow us to differentiate the disease from chronic HP or advanced-stage sarcoidosis."

HRCT findings distinguishing IPF from chronic HP are explicitly described.

Pulmonary Sarcoidosis MONDO:0019338

Overlapping Features Advanced-stage sarcoidosis can present with fibrotic lung changes but shows a characteristic upper and mid-lung predominance on HRCT.

Distinguishing Features

Upper and middle lung zone predominance with lung bases usually spared
Reticulation, traction bronchiectasis, architectural distortion, and honeycomblike cysts

Show evidence (1 reference)

PMID:24480143 SUPPORT Human Clinical

"In advanced-stage sarcoidosis, patchy areas of reticulation, traction bronchiectasis, architectural distortion, honeycomblike cysts, bullae, and paracicatricial emphysema are observed in the upper and middle lung zones. Lung bases are usually spared."

The abstract details HRCT patterns that distinguish advanced-stage sarcoidosis from chronic HP.

Hypersensitivity Pneumonitis from Home Mold Exposure MONDO:0017853

Overlapping Features Non-avian hypersensitivity pneumonitis triggered by home mold exposure can present with similar ILD features.

Distinguishing Features

Home mold exposure identified as culprit antigen
Similar ILD features without avian exposure history

Show evidence (1 reference)

PMID:40338891 SUPPORT Human Clinical

"Home mold exposure was identified as the culprit antigen in 54 of 231 hypersensitivity pneumonitis patients."

The cohort documents HP driven by home mold exposure, supporting mold-related HP as a non-avian differential diagnosis.

📊

Related Datasets

RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung geo:GSE150910

Bulk RNA-seq of whole lung tissue from chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, and controls. The HP samples are not stratified by inciting antigen, so this is shared HP context rather than a BFL-specific cohort.

human BULK RNA SEQ

lung tissue UBERON:0002048

Conditions: hypersensitivity pneumonitis idiopathic pulmonary fibrosis normal lung

PMID:32602730

GEO record includes HP, IPF, and control whole-lung RNA-seq samples; avian exposure status is not supplied at dataset level.

Show evidence (1 reference)

PMID:32602730 SUPPORT Human Clinical

"Transcriptome analysis of lung samples from CHP (n = 82), IPF (n = 103), and unaffected controls (n = 103) was conducted."

The study reports bulk transcriptome profiling of lung samples from chronic HP, IPF, and controls, matching the dataset description.

Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis geo:GSE271789

Single-cell and single-nucleus RNA-seq of PBMCs and BAL cells from fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, and controls. The HP cohort is not stratified by inciting antigen.

human SINGLE CELL RNA SEQ

peripheral blood mononuclear cell CL:2000001 bronchoalveolar lavage NCIT:C13195

Conditions: fibrotic hypersensitivity pneumonitis idiopathic pulmonary fibrosis healthy control

PMID:38924775

GEO record linked to the AJRCCM 2024 single-cell study profiling PBMC and BAL; it informs shared fibrotic-HP mechanisms rather than a proven avian-specific program.

Show evidence (1 reference)

PMID:38924775 SUPPORT Human Clinical

The abstract documents single-cell sequencing of PBMC and BAL cells from fibrotic HP, IPF, and controls, aligning with the dataset.

🔬

Clinical Trials

NCT02958917 PHASE_II TERMINATED

Randomized, double-blind, placebo-controlled study evaluating pirfenidone in fibrotic hypersensitivity pneumonitis.

Target Phenotypes: Dyspnea HP:0002094 Pulmonary fibrosis HP:0002206

Show evidence (1 reference)

clinicaltrials:NCT02958917 SUPPORT Human Clinical

"Patients are being offered participation in this pirfenidone trial because They have been diagnosed with fibrotic hypersensitivity pneumonitis (FHP), a type of interstitial lung disease (ILD)."

The registry entry specifies the trial population and disease focus.

NCT02496182 PHASE_II UNKNOWN

Study evaluating addition of pirfenidone to prednisone and azathioprine in chronic hypersensitivity pneumonitis with pulmonary fibrosis.

Target Phenotypes: Pulmonary fibrosis HP:0002206 Cough HP:0012735

Show evidence (1 reference)

clinicaltrials:NCT02496182 SUPPORT Human Clinical

"the investigators propose to evaluate the addition of Pirfenidone to the actual treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis."

The registry summary outlines treatment strategy and target population.

NCT04844359 NOT_APPLICABLE ACTIVE_NOT_RECRUITING

Observational study developing and validating a prognostic blood transcriptomic signature in chronic hypersensitivity pneumonitis.

Target Phenotypes: Pulmonary fibrosis HP:0002206 Dyspnea HP:0002094

Show evidence (1 reference)

clinicaltrials:NCT04844359 SUPPORT Human Clinical

"Up to 150 patients with hypersensitivity pneumonitis will be enrolled at 7 clinical centers across the United States. Patients will be followed for 24 months to determine if biomarkers in the blood can predict disease progression."

The registry summary describes enrollment and biomarker-focused outcomes.

🐁

Animal Models

Mus musculus

Mouse model sensitized with pigeon serum and challenged intranasally to induce bird-related hypersensitivity pneumonitis.

Species

Mus musculus

Show evidence (1 reference)

DOI:10.3390/ijms24032884 SUPPORT Model Organism

"On days −3 and −1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2)."

The study describes a pigeon serum-induced mouse model of BRHP.

Mus musculus

Pigeon breeder's lung model generated by tracheal instillation of pigeon dropping extract protein powder.

Species

Mus musculus

Show evidence (1 reference)

PMID:39844643 SUPPORT Model Organism

"PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder."

The study establishes a pigeon breeder's lung mouse model using pigeon dropping extract.

{ }

Source YAML

click to show

name: Bird Fancier's Lung
creation_date: '2026-01-30T23:42:47Z'
category: Respiratory Disease
parents:
- Respiratory Disease
- Inflammatory Lung Disease
classifications:
  harrisons_chapter:
  - classification_value: RESPIRATORY
    evidence:
    - reference: DOI:10.3390/ijms24032884
      reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins.
      explanation: The source directly classifies bird-related HP as an interstitial lung disease.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0005668
      label: bird fancier's lung
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: MONDO:0005668 is the primary disease term for bird fancier's lung.
external_assertions:
- name: ATS/JRS/ALAT adult hypersensitivity pneumonitis diagnostic guideline
  source: ATS/JRS/ALAT
  assertion_type: clinical_practice_guideline
  external_id: PMID:32706311
  url: https://pubmed.ncbi.nlm.nih.gov/32706311/
  description: >-
    The official adult HP guideline supplies the nonfibrotic/fibrotic
    classification and multidisciplinary diagnostic framework applied to this
    avian-antigen subtype.
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: HP was classified into nonfibrotic and fibrotic phenotypes.
    explanation: The official guideline establishes the current phenotype-based classification.
- name: German S2k hypersensitivity pneumonitis diagnosis and treatment guideline
  source: German Respiratory Society and German Society for Allergology and Clinical Immunology
  assertion_type: clinical_practice_guideline
  external_id: PMID:39870058
  url: https://pubmed.ncbi.nlm.nih.gov/39870058/
  description: >-
    The 2025 S2k guideline adds treatment recommendations and distinguishes
    inflammatory and fibrotic patterns across acute and chronic HP courses.
  evidence:
  - reference: PMID:39870058
    reference_title: "Diagnosis and Treatment of Hypersensitivity Pneumonitis: S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Particular emphasis was placed on the different clinical courses (acute
      and chronic) and their characteristics (inflammatory and/or fibrotic
      pattern), which present differential diagnostic challenges and ultimately
      result in different treatment approaches.
    explanation: The guideline explicitly links phenotype and clinical course to treatment strategy.
has_subtypes:
- name: Nonfibrotic bird-related hypersensitivity pneumonitis
  description: >-
    Bird-related HP without radiologic or histopathologic evidence of fibrosis;
    it often has a clearer exposure history, acute inflammatory features, and
    bronchoalveolar-lavage lymphocytosis.
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      nonfibrotic HP (i.e., patients without radiological and/or
      histopathological evidence of fibrosis)
    explanation: The guideline defines the nonfibrotic phenotype by absence of fibrosis.
- name: Fibrotic bird-related hypersensitivity pneumonitis
  description: >-
    Bird-related HP with radiologic or histopathologic fibrosis; exposure may be
    less obvious and the course may become progressive despite antigen removal.
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      fibrotic HP (i.e., patients with radiological and/or histopathological
      evidence of fibrosis)
    explanation: The guideline defines the fibrotic phenotype by demonstrable fibrosis.
- name: Recurrent chronic bird fancier's lung
  description: >-
    Historical chronic-BFL pattern with recurrent acute episodes followed by
    interstitial pulmonary fibrosis; retained as a bird-specific clinical
    course rather than as the primary modern classification.
  evidence:
  - reference: PMID:12839317
    reference_title: "Clinical features of recurrent and insidious chronic bird fancier's lung."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent BFL)"
    explanation: The abstract defines a recurrent chronic BFL subtype marked by recurrent acute episodes and fibrotic progression.
- name: Insidious chronic bird fancier's lung
  description: >-
    Historical chronic-BFL pattern with slowly progressive respiratory disease
    and no recalled acute episodes; retained as a bird-specific clinical
    course rather than as the primary modern classification.
  evidence:
  - reference: PMID:12839317
    reference_title: "Clinical features of recurrent and insidious chronic bird fancier's lung."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the other subgroup of patients has no history of acute episodes but has slowly progressive chronic respiratory disease (insidious BFL)."
    explanation: The abstract defines an insidious subtype with slow progression and no acute episode history.
disease_term:
  preferred_term: bird fancier's lung
  term:
    id: MONDO:0005668
    label: bird fancier's lung
description: >-
  Bird fancier's lung is the avian-antigen form of hypersensitivity pneumonitis:
  an immune-mediated interstitial and small-airway lung disease caused by
  repeated inhalation of proteins from birds, feathers, or contaminated
  materials. It spans nonfibrotic inflammatory and fibrotic phenotypes; only a
  minority of exposed people develop disease.
synonyms:
- Bird-related hypersensitivity pneumonitis
- Bird-related HP
- BRHP
- Avian hypersensitivity pneumonitis
- Avian HP
- Bird fancier's lung
- Pigeon breeder's disease
- Pigeon breeders' disease
- Pigeon fancier's lung
epidemiology:
- name: Salt Lake City pigeon-fancier cohort
  description: >-
    A selected regional cohort found clinical pigeon breeders' disease in 21%
    of 53 pigeon fanciers; this exposure-cohort proportion is not a general
    population prevalence estimate.
  evidence:
  - reference: PMID:1053441
    reference_title: "Pigeon breeders' disease--a prevalence study and review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among fifty-three Salt Lake City, Utah area pigeon fanciers, 21% were found to have the clinical picture of pigeon breeders' disease."
    explanation: The study supplies a cohort-specific proportion among heavily exposed pigeon fanciers.
- name: Common form of hypersensitivity pneumonitis
  description: Bird fancier's lung is a common form of hypersensitivity pneumonitis among exposed populations.
  evidence:
  - reference: PMID:21870048
    reference_title: "Bird fancier's lung: a state-of-the-art review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Bird fancier's lung (BFL) resulting from avian antigen exposure is a very common form of hypersensitivity pneumonitis."
    explanation: The review describes BFL as a very common form of HP.
progression:
- phase: Acute inflammatory presentation
  notes: >-
    An acute presentation can begin within hours after a high avian-antigen
    exposure and commonly aligns with a nonfibrotic inflammatory phenotype.
  evidence:
  - reference: PMID:6761066
    reference_title: "Immunology of hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Symptoms usually begin 4 to 6 hr after exposure to large quantities of causative organic dust."
    explanation: The review describes rapid onset after exposure in acute disease.
- phase: Chronic fibrotic presentation
  notes: >-
    Chronic disease can begin gradually and develop pulmonary fibrosis; the
    current fibrotic/nonfibrotic phenotype should be recorded separately from
    the time course.
  evidence:
  - reference: PMID:6761066
    reference_title: "Immunology of hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Chronically, these diseases may present with the gradual onset of cough, dyspnea on exertion, fatigue, anorexia, and weight loss which may progress to pulmonary fibrosis or severe pulmonary insufficiency."
    explanation: The review notes gradual onset and progression to fibrosis.
- phase: Progressive fibrotic disease
  notes: >-
    Once a progressive fibrotic phenotype is established, decline may continue
    despite removal of the identified exposure.
  evidence:
  - reference: PMID:32764620
    reference_title: Hypersensitivity pneumonitis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Some patients with fibrotic HP may evolve to a progressive phenotype,
      even with complete exposure avoidance.
    explanation: The review establishes that exposure removal does not invariably halt fibrotic progression.
pathophysiology:
- name: Exposure to Avian Proteins
  description: Repeated inhalation of avian proteins from bird droppings, feathers, or serum triggers bird-related hypersensitivity pneumonitis.
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: DOI:10.3390/ijms24032884
    reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins."
    explanation: The review defines BRHP as an avian protein-induced interstitial lung disease.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bird fancier's lung (BFL) is a subtype of hypersensitivity pneumonitis (HP), an immune-mediated interstitial lung disease (ILD) resulting from the repeated inhalation of avian proteins found in bird droppings, feathers, and serum."
    explanation: The case report links BFL to repeated inhalation of avian proteins as the causative trigger for interstitial lung disease.
  - reference: PMID:33318919
    reference_title: "Bird Fancier's lung: An underdiagnosed etiology of dyspnea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bird Fancier's Lung is a type of hypersensitivity pneumonitis, an immunologically mediated lung disease due to repetitive exposure of air-borne avian antigen."
    explanation: The report characterizes BFL as an immune-mediated interstitial lung disease driven by repetitive avian antigen exposure.
  downstream:
  - target: Bird Antigen-Driven Humoral Response
    description: >-
      Repeated avian antigen exposure triggers measurable bird-specific
      antibody responses.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:33041192
      reference_title: "Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The levels of sIgG/sIgA against the bird antigens of the three species
        were significantly higher in subjects with acute bird-related HP and
        chronic bird-related HP with acute episodes (recurrent type) than in
        the control subjects.
      explanation: Bird-related HP is associated with measurable avian-antigen-specific antibody responses.
  - target: Th1/Th2 to Th2/Th17 Cytokine Shift
    description: >-
      Antigen exposure initiates the hypersensitivity-pneumonitis immune
      response that shifts across disease stages.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: DOI:10.3390/ijms24032884
      reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        In the first stages of BRHP, there is a mixed Th1/Th2 immune response,
        while during the progression of the disease, although there is a Th1
        response, the cytokine levels seem to indicate a switch towards a
        Th2/Th17 mixed response.
      explanation: The pigeon-serum mouse model supplies stage-dependent cytokine evidence.
  - target: Inflammatory Alveolar and Interstitial Lung Injury
    description: >-
      Repeated avian antigen exposure initiates immune-mediated inflammation in
      the small airways, alveoli, and interstitium.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:39958101
      reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Bird fancier's lung (BFL) is a subtype of hypersensitivity pneumonitis
        (HP), an immune-mediated interstitial lung disease (ILD) resulting from
        the repeated inhalation of avian proteins found in bird droppings,
        feathers, and serum.
      explanation: Human BFL evidence connects repeated avian exposure to immune-mediated interstitial injury.
- name: Expansion of Resident Monocytes and Interstitial Macrophages
  description: Bird antigen exposure is associated with increased resident monocytes, interstitial macrophages, and type 2 dendritic cells in the lung.
  cell_types:
  - preferred_term: monocyte
    term:
      id: CL:0000576
      label: monocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: DOI:10.3390/ijms24032884
    reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups."
    explanation: The mouse model reports increased resident monocytes, interstitial macrophages, and type 2 dendritic cells after bird antigen exposure.
  downstream:
  - target: Th1/Th2 to Th2/Th17 Cytokine Shift
    description: >-
      Monocyte, macrophage, and dendritic-cell remodeling is modeled upstream
      of the stage-dependent T-cell cytokine shift.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: DOI:10.3390/ijms24032884
      reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Both groups presented increases in resident monocytes, interstitial
        macrophages and type 2 dendritic cells (DCs), but also reductions in
        inflammatory monocytes, alveolar macrophages and tolerogenic DCs
        compared with their control groups.
      explanation: The same pigeon-serum model places myeloid-cell remodeling in the immune-response branch.
- name: Reduction of Inflammatory Monocytes and Alveolar Macrophages
  description: Bird antigen exposure is associated with reduced inflammatory monocytes, alveolar macrophages, and tolerogenic dendritic cells in the lung.
  cell_types:
  - preferred_term: monocyte
    term:
      id: CL:0000576
      label: monocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  - preferred_term: alveolar macrophage
    term:
      id: CL:0000583
      label: alveolar macrophage
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: DOI:10.3390/ijms24032884
    reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups."
    explanation: The same experiment reports reduced inflammatory monocytes, alveolar macrophages, and tolerogenic dendritic cells.
  downstream:
  - target: Th1/Th2 to Th2/Th17 Cytokine Shift
    description: >-
      Reduced inflammatory monocytes, alveolar macrophages, and tolerogenic
      dendritic cells are modeled as part of the myeloid-cell remodeling
      upstream of the stage-dependent cytokine shift.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: DOI:10.3390/ijms24032884
      reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Both groups presented increases in resident monocytes, interstitial
        macrophages and type 2 dendritic cells (DCs), but also reductions in
        inflammatory monocytes, alveolar macrophages and tolerogenic DCs
        compared with their control groups. Group 1 had increased levels of
        eosinophils and T cells with reductions in neutrophils and B cells,
        while Group 2 showed high levels of B cells. Both groups exhibited
        increases in Th1 and Th2 cytokines. Group 2 also showed increased levels
        of IL-23, a Th17 cytokine.
      explanation: >-
        The pigeon-serum model co-documents reduced myeloid and tolerogenic
        populations with Th1/Th2 cytokine increases and a later IL-23/Th17
        signal. The indirect edge models this association, not a proven direct
        mechanism.
- name: Th1/Th2 to Th2/Th17 Cytokine Shift
  description: Early disease shows a mixed Th1/Th2 response, while progression shifts toward a Th2/Th17 mixed response.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  biological_processes:
  - preferred_term: T cell activation
    term:
      id: GO:0042110
      label: T cell activation
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: DOI:10.3390/ijms24032884
    reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response."
    explanation: The cytokine profile indicates a stage-dependent shift toward Th2/Th17 responses during disease progression.
  downstream:
  - target: Inflammatory Alveolar and Interstitial Lung Injury
    description: >-
      The stage-dependent T-cell cytokine program participates in the
      inflammatory lung response measured in the pigeon-serum model.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: DOI:10.3390/ijms24032884
      reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also
        showed increased levels of IL-23, a Th17 cytokine. Increased levels of
        neutrophils, eosinophils and lymphocytes were observed in BAL samples
        of both groups compared with controls.
      explanation: Cytokine and BAL inflammatory-cell changes co-occur in the bird-antigen model.
- name: Inflammatory Alveolar and Interstitial Lung Injury
  description: >-
    Avian-antigen-driven immune responses produce mononuclear alveolitis and
    interstitial/small-airway inflammation, impairing gas exchange and causing
    acute and chronic respiratory symptoms.
  cell_types:
  - preferred_term: mononuclear cell
    term:
      id: CL:0000842
      label: mononuclear leukocyte
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: alveolus of lung
    term:
      id: UBERON:0002299
      label: alveolus of lung
  - preferred_term: lung connective tissue
    term:
      id: UBERON:0000114
      label: lung connective tissue
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: a transbronchial lung biopsy (TBLB) specimen showed alveolitis due to the infiltration of mononuclear cells.
    explanation: A human feather-associated BFL case directly documents mononuclear alveolitis.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bird fancier's lung (BFL) is a subtype of hypersensitivity pneumonitis
      (HP), an immune-mediated interstitial lung disease (ILD) resulting from
      the repeated inhalation of avian proteins found in bird droppings,
      feathers, and serum.
    explanation: The clinical report identifies the interstitial inflammatory compartment in human BFL.
  downstream:
  - target: Dyspnea
    description: Active interstitial and alveolar inflammation produces breathlessness.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:14503346
      reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks.
      explanation: A biopsy-confirmed BFL case co-documents inflammatory lung disease and shortness of breath.
  - target: Cough
    description: Small-airway and interstitial inflammation produces cough.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:14503346
      reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks.
      explanation: A biopsy-confirmed BFL case co-documents alveolitis and cough.
  - target: Fever
    description: Acute inflammatory episodes can produce fever.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:14503346
      reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks.
      explanation: The human BFL case directly reports low-grade fever during active disease.
  - target: Fatigue
    description: Chronic inflammatory HP can produce systemic fatigue.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:6761066
      reference_title: Immunology of hypersensitivity pneumonitis.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Chronically, these diseases may present with the gradual onset of cough,
        dyspnea on exertion, fatigue, anorexia, and weight loss which may
        progress to pulmonary fibrosis or severe pulmonary insufficiency.
      explanation: General HP evidence supports fatigue downstream of chronic inflammatory lung disease.
  - target: Hypoxemia
    description: Alveolar and interstitial injury can impair pulmonary gas exchange.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:11131880
      reference_title: "[A misleading form of hypersensitivity pneumonitis]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        A 47-year-old woman, without significant past medical history,
        presented an acute dyspnea with hypoxia, marked pulmonary arterial
        hypertension (PAH) and signs of right heart failure.
      explanation: A bird-associated HP case documents hypoxia during acute respiratory disease.
  - target: Pulmonary Fibrosis
    description: Persistent inflammatory injury can progress to fibrotic remodeling.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Recurrent epithelial injury and fibroblast activation remodel the lung interstitium.
    evidence:
    - reference: PMID:6761066
      reference_title: Immunology of hypersensitivity pneumonitis.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Chronically, these diseases may present with the gradual onset of cough,
        dyspnea on exertion, fatigue, anorexia, and weight loss which may
        progress to pulmonary fibrosis or severe pulmonary insufficiency.
      explanation: The review explicitly connects chronic HP to progression toward pulmonary fibrosis.
- name: Bird Antigen-Driven Humoral Response
  description: Bird antigen exposure triggers B cell activation and elevated serum IgG/IgA to avian proteins in bird-related hypersensitivity pneumonitis.
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: B cell activation
    term:
      id: GO:0042113
      label: B cell activation
  - preferred_term: antigen processing and presentation
    term:
      id: GO:0019882
      label: antigen processing and presentation
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:33041192
    reference_title: "Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects."
    explanation: Elevated bird-specific IgG/IgA in affected patients supports a humoral immune response to avian antigens.
  downstream:
  - target: Inflammatory Alveolar and Interstitial Lung Injury
    description: >-
      Antigen-specific humoral responses participate with T-cell responses in
      lymphocytic and granulomatous lung inflammation.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Antigen-specific IgG and Th1 cellular responses accompany lymphocytic and granulomatous inflammation.
    evidence:
    - reference: PMID:32706311
      reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        In sensitized individuals, the immune reaction after exposure to an
        antigen appears to consist of both humoral (i.e., antigen-specific IgG
        antibodies) and T-helper cell type 1 (Th1) cellular immune responses
        (83, 88). These responses lead to a predominantly lymphocytic
        inflammatory pattern and granulomatous inflammation (11, 75, 89).
      explanation: The guideline explicitly connects humoral and cellular responses to inflammatory lung pathology.
- name: Classical Monocyte Enrichment
  description: >-
    Fibrotic-HP cohorts not stratified by inciting antigen show elevated
    classical monocytes enriched for CCL3hi/CCL4hi and S100Ahi states. This is
    shared fibrotic-HP evidence, not a bird-specific result.
  cell_types:
  - preferred_term: monocyte
    term:
      id: CL:0000576
      label: monocyte
  biological_processes:
  - preferred_term: chemokine-mediated signaling pathway
    term:
      id: GO:0070098
      label: chemokine-mediated signaling pathway
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:38924775
    reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Compared with control samples, FHP has elevated classical monocytes (adjusted-P = 2.5 × 10-3) and is enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-P < 2.2 × 10-16)."
    explanation: Single-cell profiling identifies enriched states in fibrotic HP without avian-antigen stratification.
  downstream:
  - target: Monocyte-to-SPP1hi Macrophage Differentiation
    description: >-
      Enriched classical monocyte states feed the profibrotic macrophage
      differentiation trajectory.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38924775
      reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis.
      explanation: The trajectory directly supports this transition in non-antigen-stratified fibrotic HP.
- name: Monocyte-to-SPP1hi Macrophage Differentiation
  description: >-
    In non-antigen-stratified fibrotic HP, S100Ahi classical monocytes
    differentiate toward SPP1hi lung macrophages associated with fibrosis; the
    branch is extrapolated to fibrotic BFL.
  cell_types:
  - preferred_term: monocyte
    term:
      id: CL:0000576
      label: monocyte
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:38924775
    reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis."
    explanation: Trajectory analyses link classical monocytes to profibrotic macrophages in general fibrotic HP.
  downstream:
  - target: Pulmonary Fibrosis
    description: >-
      SPP1-high lung macrophages are associated with the fibrotic remodeling
      phenotype in fibrotic hypersensitivity pneumonitis.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38924775
      reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis.
      explanation: The source associates the terminal macrophage state with fibrosis in general fibrotic HP.
- name: Cytotoxic T Cell Program with Profibrotic Signaling
  description: >-
    Non-antigen-stratified fibrotic HP features GZMhi cytotoxic T cells with
    transcriptional programs implicating TGFβ, TNFα, and NFκB pathways; this
    branch is shared-context evidence for fibrotic BFL.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  biological_processes:
  - preferred_term: T cell activation
    term:
      id: GO:0042110
      label: T cell activation
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:38924775
    reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Compared with both control subjects and IPF, cells from patients with FHP are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit TF activities indicative of TGFβ and TNFα and NFκB pathways."
    explanation: Cytotoxic T cell enrichment with profibrotic signaling programs supports a T cell-driven inflammatory mechanism.
  downstream:
  - target: Pulmonary Fibrosis
    description: >-
      Cytotoxic T cells with TGF-beta, TNF-alpha, and NF-kappaB programs are
      modeled as part of the profibrotic inflammatory branch.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:38924775
      reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Compared with both control subjects and IPF, cells from patients with
        FHP are significantly enriched in GZMhi cytotoxic T cells. These cells
        exhibit TF activities indicative of TGFβ and TNFα and NFκB pathways.
      explanation: The fibrotic-HP cohort supports association with profibrotic signaling, not bird-specific causation.
- name: MMP14-High Macrophage Profibrotic Activity
  description: >-
    In a non-avian Saccharopolyspora rectivirgula-antigen HP model, MMP14-high
    M2-like macrophages promote fibroblast-to-myofibroblast transition. This
    informs a shared HP-fibrosis mechanism but is an extrapolation to BFL.
  cell_types:
  - preferred_term: alveolar macrophage
    term:
      id: CL:0000583
      label: alveolar macrophage
  biological_processes:
  - preferred_term: extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
  locations:
  - preferred_term: alveolus of lung
    term:
      id: UBERON:0002299
      label: alveolus of lung
  evidence:
  - reference: PMID:38218353
    reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT)."
    explanation: The non-avian HP model identifies a macrophage subset driving fibroblast-to-myofibroblast transition.
  downstream:
  - target: Pulmonary Fibrosis
    description: >-
      MMP14-high macrophage promotion of fibroblast-to-myofibroblast transition
      contributes to pulmonary fibrosis.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38218353
      reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag.
      explanation: Transfer experiments causally support fibrosis in the non-avian HP model.
- name: TLR2 and NF-κB Regulation of MMP14 and Exosome Secretion
  description: >-
    In the non-avian SR-antigen HP model, TLR2 and NF-κB signaling regulate
    macrophage MMP14 expression and exosome secretion; applicability to BFL is
    not yet directly established.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  evidence:
  - reference: PMID:38218353
    reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag."
    explanation: The abstract links TLR2/NF-κB signaling to MMP14 regulation and exosome secretion in HP macrophages.
  downstream:
  - target: MMP14-High Macrophage Profibrotic Activity
    description: >-
      TLR2 and NF-kappaB signaling regulate the MMP14-high macrophage
      profibrotic program.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38218353
      reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag.
      explanation: Perturbation supports TLR2/NF-κB control of the MMP14 program in the non-avian model.
phenotypes:
- category: Respiratory
  name: Dyspnea
  frequency: FREQUENT
  description: Exertional or progressive shortness of breath associated with inflammatory and fibrotic lung involvement.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."
    explanation: The case report documents shortness of breath in bird fancier's lung.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We present the case of a 43-year-old male pigeon keeper with an eight-week history of progressive dyspnea on exertion and intermittent chest pain."
    explanation: The case report describes progressive dyspnea on exertion in BFL.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common symptoms and signs of both nonfibrotic and fibrotic HP include
      dyspnea, cough, and midinspiratory squeaks (or chirping rales or squawks)
      (32).
    explanation: >-
      The guideline's qualitative term "Common" maps to FREQUENT under the
      DisMech frequency-evidence SOP. Because the source covers HP broadly
      rather than an avian-antigen subgroup, it is retained as PARTIAL support
      for the BFL frequency band.
- category: Respiratory
  name: Cough
  frequency: FREQUENT
  description: Persistent or recurrent cough associated with hypersensitivity pneumonitis.
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."
    explanation: The case report describes cough in bird fancier's lung.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common symptoms and signs of both nonfibrotic and fibrotic HP include
      dyspnea, cough, and midinspiratory squeaks (or chirping rales or squawks)
      (32).
    explanation: >-
      The guideline's qualitative term "Common" maps to FREQUENT under the
      DisMech frequency-evidence SOP. Because the source covers HP broadly
      rather than an avian-antigen subgroup, it is retained as PARTIAL support
      for the BFL frequency band.
- category: Respiratory
  name: Pulmonary Fibrosis
  description: Fibrotic remodeling in chronic or progressive disease.
  phenotype_term:
    preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: PMID:37028940
    reference_title: "Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality."
    explanation: The trial focuses on fibrotic hypersensitivity pneumonitis, supporting pulmonary fibrosis as a clinical phenotype.
  - reference: PMID:32145830
    reference_title: "Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis"
    explanation: The INBUILD subgroup analysis includes hypersensitivity pneumonitis within progressive fibrosing ILD populations, supporting a fibrotic phenotype.
  - reference: PMID:24480143
    reference_title: "Chronic hypersensitivity pneumonitis and pulmonary sarcoidosis: differentiation from usual interstitial pneumonia using high-resolution computed tomography."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the 3 diseases, most important prognosis-predicting factor is the extent of fibrotic score (the extent of honeycombing and reticulation) calculated on high-resolution computed tomography scans or fibrosis estimated on chest radiographs."
    explanation: Chronic HP is discussed alongside fibrotic scoring on HRCT, reinforcing pulmonary fibrosis as a key disease feature.
  - reference: PMID:38218353
    reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag."
    explanation: In a hypersensitivity pneumonitis model, fibrosis is a documented outcome, supporting pulmonary fibrosis as a disease phenotype.
- category: Respiratory
  name: Hypoxemia
  description: Reduced blood oxygenation during active disease.
  phenotype_term:
    preferred_term: Hypoxemia
    term:
      id: HP:0012418
      label: Hypoxemia
  evidence:
  - reference: PMID:11131880
    reference_title: "[A misleading form of hypersensitivity pneumonitis]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure."
    explanation: The case demonstrates hypoxia as part of acute bird hypersensitivity pneumonitis.
- category: Constitutional
  name: Fatigue
  description: Systemic fatigue during symptomatic episodes.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:6761066
    reference_title: "Immunology of hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Chronically, these diseases may present with the gradual onset of cough, dyspnea on exertion, fatigue, anorexia, and weight loss which may progress to pulmonary fibrosis or severe pulmonary insufficiency."
    explanation: The clinical review describes fatigue among chronic hypersensitivity pneumonitis presentations.
- category: Constitutional
  name: Fever
  description: Flu-like systemic symptoms during acute exposure episodes.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks."
    explanation: The case report documents low-grade fever in bird fancier's lung.
histopathology:
- name: Alveolitis with Mononuclear Infiltration
  description: Transbronchial lung biopsy may show alveolitis due to mononuclear cell infiltration.
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a transbronchial lung biopsy (TBLB) specimen showed alveolitis due to the infiltration of mononuclear cells."
    explanation: The case report documents biopsy-confirmed alveolitis in bird fancier's lung.
- name: Bronchiolocentric Interstitial Pneumonia with Granulomatous Inflammation
  description: >-
    Typical nonfibrotic HP histology combines bronchiolocentric cellular
    interstitial pneumonia, chronic bronchiolitis, and poorly formed
    nonnecrotizing granulomatous inflammation. These findings support BFL only
    when integrated with avian exposure and the other diagnostic domains.
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      A confident histopathological diagnosis of nonfibrotic HP requires the
      presence of typical histopathological features. These include 1) a
      cellular interstitial pneumonia accentuated around small airways
      (“bronchiolocentric”) accompanied by 2) a cellular chronic bronchiolitis,
      3) a distinctive pattern of granulomatous inflammation, and 4) no
      histopathological features to suggest a more likely alternative
    explanation: The official guideline defines the characteristic nonfibrotic-HP histologic triad.
biochemical:
- name: Bird antigen-specific IgG/IgA antibodies
  notes: Elevated serum IgG/IgA antibodies to bird antigens in bird-related hypersensitivity pneumonitis.
  presence: Positive
  evidence:
  - reference: PMID:33041192
    reference_title: "Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects."
    explanation: Elevated bird-specific antibodies are reported in affected patients.
  - reference: PMID:38762468
    reference_title: "Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP."
    explanation: The study uses serial bird-specific IgG testing against pigeon serum in fibrotic avian HP.
  - reference: PMID:40049235
    reference_title: "Anti-chicken and anti-pigeon immunoglobulin G testing in patients with bird-related fibrotic hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mean titers of anti-pigeon IgG antibody by ELISA were 0.659 ± 0.381 and 0.494 ± 0.187 in the bird-related fibrotic HP and control groups, respectively (p = 0.012)."
    explanation: Anti-pigeon IgG titers are higher in bird-related fibrotic HP, supporting serologic evidence for avian antigen exposure.
diagnosis:
- name: Multidisciplinary diagnostic integration
  description: >-
    BFL is diagnosed by integrating avian exposure assessment, thoracic HRCT,
    BAL cellular analysis, and—when needed—histopathology in multidisciplinary
    discussion. No single feature is sufficient in isolation.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:33861992
    reference_title: "Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Diagnosis of HP should employ a patient-centered approach and include a
      multidisciplinary assessment that incorporates the environmental and
      occupational exposure history and CT pattern to establish diagnostic
      confidence prior to considering BAL and/or lung biopsy.
    explanation: The CHEST guideline defines the multidisciplinary sequence used for suspected avian HP.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Although the diagnosis of HP is predominantly based on exposure
      identification, chest HRCT scan pattern, and
      bronchoscopic/histopathological findings, a major challenge is that no
      individual feature is sufficient in isolation, nor are any mandatory.
    explanation: The official guideline cautions against treating any one diagnostic domain as definitive.
- name: Avian and occupational exposure history
  description: >-
    A structured history should assess live birds, droppings, feathers or down
    bedding, contaminated fertilizer, occupational sources, and indirect
    household exposure.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Pending the availability of a validated questionnaire, the guideline
      committee advocates that clinicians take a thorough history to identify
      potential exposures and sources in the patient’s environment that are
      known to be associated with HP.
    explanation: The guideline prioritizes systematic exposure history.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: A thorough occupational history uncovered significant avian antigen exposure, and a family history suggested genetic susceptibility.
    explanation: A BFL case illustrates how detailed history establishes avian exposure.
- name: High-resolution computed tomography pattern
  description: >-
    Nonfibrotic BFL commonly shows ill-defined centrilobular nodules,
    ground-glass opacity, mosaic attenuation, and air trapping; fibrotic disease
    adds reticulation, traction bronchiectasis, or honeycombing.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:24480143
    reference_title: "Chronic hypersensitivity pneumonitis and pulmonary sarcoidosis: differentiation from usual interstitial pneumonia using high-resolution computed tomography."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In chronic HP, the presence of lobular areas of decreased attenuation and centrilobular small nodules and the absence of lower lung zone predominance are characteristically observed."
    explanation: The HRCT pattern distinguishes chronic HP from other fibrotic ILDs.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HRCT revealed bilateral diffuse centrilobular nodules, patchy ground-glass opacities, and a mosaic attenuation pattern without fibrosis, consistent with acute HP."
    explanation: The case report highlights characteristic HRCT findings in BFL.
- name: Bronchoalveolar lavage lymphocyte cellular analysis
  description: >-
    BAL lymphocytosis supports HP in the appropriate exposure and imaging
    context, particularly nonfibrotic disease, but is not a stand-alone BFL
    diagnosis.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bronchoalveolar lavage (BAL) revealed a marked increase in lymphocytes
    explanation: The case report documents BAL lymphocytosis in feather-associated BFL.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      recommends obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte
      cellular analysis (recommendation, very low confidence in the estimated
      effects).
    explanation: The guideline recommends BAL lymphocyte analysis for suspected nonfibrotic HP while grading the evidence as very low confidence.
- name: Bird antigen-specific IgG serology as exposure support
  description: >-
    Elevated bird-specific IgG can support prior exposure and sensitization,
    but it neither proves that birds caused the lung disease nor independently
    confirms or excludes BFL. IgA testing has been studied but is not part of
    the standard guideline formulation.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:33041192
    reference_title: "Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects."
    explanation: The bird-specific study shows group-level discrimination, supporting exposure attribution rather than stand-alone diagnosis.
  - reference: PMID:38762468
    reference_title: "Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP."
    explanation: Serial testing demonstrates an exposure biomarker in fibrotic avian HP.
  - reference: PMID:40049235
    reference_title: "Anti-chicken and anti-pigeon immunoglobulin G testing in patients with bird-related fibrotic hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mean titers of anti-pigeon IgG antibody by ELISA were 0.659 ± 0.381 and 0.494 ± 0.187 in the bird-related fibrotic HP and control groups, respectively (p = 0.012)."
    explanation: Elevated anti-pigeon IgG supports avian sensitization in the correct clinical context.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It was emphasized that a positive serum IgG result does not mean that the
      exposure is the cause of the lung condition; it only indicates that the
      patient has likely been exposed to a potential cause of HP at some point
      in his or her life
    explanation: The guideline directly limits serology to evidence of exposure rather than causation.
- name: Inhalation challenge test
  description: >-
    Specific avian inhalation challenge can help identify the inciting exposure
    in centers with appropriate expertise; it is a specialized component of
    exposure assessment, not a routine stand-alone test.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:35779842
    reference_title: "Validation of inhalation challenge test and serum immunoglobulin G test for bird-related fibrotic hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The inhalation challenge test for bird-related fibrotic HP was more sensitive than the anti-bird IgG antibodies."
    explanation: The comparative study supports challenge testing as a specialized exposure-attribution tool.
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Exposure assessment includes a thorough clinical history and/or serum IgG
      testing against potential antigens associated with HP and/or, in centers
      with the appropriate expertise and experience, specific inhalational
      challenge testing
    explanation: The guideline restricts specific inhalational challenge to experienced centers.
treatments:
- name: Identification and Avoidance of Avian Antigen
  description: >-
    Identify and remove the inciting avian source. Depending on the exposure,
    this can require removing birds, avoiding feather/down products, remediating
    contaminated material, and preventing indirect occupational or household
    exposure. Benefit is clearest in nonfibrotic HP; established fibrosis may
    continue to progress.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_phenotypes:
  - preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  - preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  target_mechanisms:
  - target: Exposure to Avian Proteins
    treatment_effect: INHIBITS
    evidence:
    - reference: PMID:32764620
      reference_title: Hypersensitivity pneumonitis.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Complete antigen avoidance is the mainstay of treatment.
      explanation: Removal of the inciting antigen directly interrupts the initiating exposure.
  evidence:
  - reference: PMID:32764620
    reference_title: Hypersensitivity pneumonitis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: Complete antigen avoidance is the mainstay of treatment.
    explanation: The review identifies complete antigen avoidance as first-line management.
  - reference: DOI:10.3390/jcm8010014
    reference_title: "Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FVC% and DLCO% increased in nfHP patients after exposure avoidance, while
      a positive numerical trend was seen for FVC% after exposure avoidance in
      fHP patients (p = 0.15).
    explanation: Retrospective data support lung-function improvement in nonfibrotic HP but leave benefit in fibrotic HP uncertain.
  - reference: DOI:10.1371/journal.pone.0273544
    reference_title: Impact of number and type of identified antigen on transplant-free survival in hypersensitivity pneumonitis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In our retrospective cohort, 136 patients met high or definite
      probability of HP and were included in the analysis. Median
      transplant-free survival was better in patients with antigen identified
      on clinical history alone than patients without identified antigen.
      Feather exposure was associated with improved TFS compared to patients
      without antigen identified; there was no difference in TFS between
      patients with feather exposure and either mold or live bird exposure.
    explanation: The cohort supports systematic identification of live-bird and feather exposures but does not directly test avoidance.
- name: Systemic Corticosteroids for Inflammatory Disease
  description: >-
    Systemic glucocorticoids such as prednisone are used for clinically
    significant inflammatory/nonfibrotic HP. Observational evidence does not
    establish a survival benefit, and the same cohort found no therapeutic
    effect in fibrotic HP.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: prednisone
      term:
        id: CHEBI:8382
        label: prednisone
  target_phenotypes:
  - preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  - preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  target_mechanisms:
  - target: Inflammatory Alveolar and Interstitial Lung Injury
    treatment_effect: INHIBITS
    evidence:
    - reference: DOI:10.3390/jcm8010014
      reference_title: "Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Although nfHP patients showed FVC% and DLCO% increase after
        corticosteroid initiation, no therapeutic effect was seen in fHP
        patients.
      explanation: Phenotype-stratified observational data support an anti-inflammatory benefit only in nonfibrotic HP.
  evidence:
  - reference: DOI:10.3390/jcm8010014
    reference_title: "Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although nfHP patients showed FVC% and DLCO% increase after corticosteroid
      initiation, no therapeutic effect was seen in fHP patients.
    explanation: The retrospective cohort supports phenotype-specific benefit and limits extrapolation to fibrosis.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient was diagnosed with BFL and treated with a tapering regimen of oral corticosteroids, starting at 40 mg/day."
    explanation: A single BFL case documents corticosteroid use but cannot establish comparative efficacy.
- name: Mycophenolate Mofetil or Azathioprine as Steroid-Sparing Therapy
  description: >-
    Mycophenolate mofetil or azathioprine may be used as steroid-sparing
    immunosuppression in chronic HP. Retrospective data found improved DLCO but
    no significant FVC improvement; prospective validation is lacking.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: immunosuppressive therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
    therapeutic_agent:
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  target_phenotypes:
  - preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  target_mechanisms:
  - target: Inflammatory Alveolar and Interstitial Lung Injury
    treatment_effect: INHIBITS
    evidence:
    - reference: PMID:27816444
      reference_title: "Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Treatment with either MMF or AZA was not associated with improved FVC
        (0.5% at 1 year; P = .46) but was associated with a statistically
        significant improvement in Dlco of 4.2% (P < .001) after 1 year of
        treatment.
      explanation: Observational lung-function data support a possible steroid-sparing effect without FVC improvement.
  evidence:
  - reference: PMID:27816444
    reference_title: "Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment with either MMF or AZA was not associated with improved FVC
      (0.5% at 1 year; P = .46) but was associated with a statistically
      significant improvement in Dlco of 4.2% (P < .001) after 1 year of
      treatment.
    explanation: The retrospective study reports the limited lung-function outcome and calls for prospective trials.
- name: Nintedanib for Progressive Fibrosing Disease
  description: >-
    Nintedanib reduces FVC decline across progressive fibrosing ILDs. The
    INBUILD analysis included chronic HP, but it was not powered to prove
    benefit within the HP subgroup and did not stratify bird-related disease.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: nintedanib
      term:
        id: CHEBI:85164
        label: nintedanib
  target_phenotypes:
  - preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: PMID:32145830
    reference_title: "Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The INBUILD trial was not designed or powered to provide evidence for a
      benefit of nintedanib in specific diagnostic subgroups. However, its
      results suggest that nintedanib reduces the rate of ILD progression, as
      measured by FVC decline, in patients who have a chronic fibrosing ILD and
      progressive phenotype, irrespective of the underlying ILD diagnosis.
    explanation: The randomized trial supports the broader progressive-fibrosing-ILD indication while preserving subgroup uncertainty.
- name: Investigational Pirfenidone for Fibrotic HP
  description: >-
    A small randomized trial in progressive fibrotic HP was interrupted by the
    COVID-19 pandemic and underpowered for its primary FVC endpoint. Pirfenidone
    improved a secondary progression-free-survival endpoint but remains
    investigational for this indication.
  action_category: THERAPEUTIC
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: pirfenidone
      term:
        id: CHEBI:32016
        label: pirfenidone
  target_phenotypes:
  - preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: PMID:37028940
    reference_title: "Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The trial was underpowered to detect a difference in the primary end
      point. Pirfenidone was found to be safe and improved PFS in patients with
      FHP.
    explanation: The published trial reports a favorable secondary endpoint while explicitly acknowledging inadequate power for the primary endpoint.
  - reference: clinicaltrials:NCT02958917
    reference_title: "A Randomized, Double-Blind, Placebo-Controlled, Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The use of pirfenidone has not been approved for the treatment of FHP. It is considered experimental treatment in this study.
    explanation: The trial registry explicitly identifies pirfenidone as experimental for fibrotic HP.
differential_diagnoses:
- name: Idiopathic Pulmonary Fibrosis
  disease_term:
    preferred_term: idiopathic pulmonary fibrosis
    term:
      id: MONDO:0800504
      label: idiopathic pulmonary fibrosis
  description: Idiopathic pulmonary fibrosis can mimic chronic hypersensitivity pneumonitis with dyspnea and fibrosis, but has distinct HRCT distribution and feature patterns.
  distinguishing_features:
  - Honeycombing with lower lung zone predominance on HRCT
  - Absence of centrilobular small nodules
  evidence:
  - reference: PMID:24480143
    reference_title: "Chronic hypersensitivity pneumonitis and pulmonary sarcoidosis: differentiation from usual interstitial pneumonia using high-resolution computed tomography."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In idiopathic pulmonary fibrosis or usual interstitial pneumonia, however, the presence of honeycombing with lower lung zone predominance and the absence of centrilobular small nodules are important findings that allow us to differentiate the disease from chronic HP or advanced-stage sarcoidosis."
    explanation: HRCT findings distinguishing IPF from chronic HP are explicitly described.
- name: Pulmonary Sarcoidosis
  disease_term:
    preferred_term: sarcoidosis
    term:
      id: MONDO:0019338
      label: sarcoidosis
  description: Advanced-stage sarcoidosis can present with fibrotic lung changes but shows a characteristic upper and mid-lung predominance on HRCT.
  distinguishing_features:
  - Upper and middle lung zone predominance with lung bases usually spared
  - Reticulation, traction bronchiectasis, architectural distortion, and honeycomblike cysts
  evidence:
  - reference: PMID:24480143
    reference_title: "Chronic hypersensitivity pneumonitis and pulmonary sarcoidosis: differentiation from usual interstitial pneumonia using high-resolution computed tomography."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In advanced-stage sarcoidosis, patchy areas of reticulation, traction bronchiectasis, architectural distortion, honeycomblike cysts, bullae, and paracicatricial emphysema are observed in the upper and middle lung zones. Lung bases are usually spared."
    explanation: The abstract details HRCT patterns that distinguish advanced-stage sarcoidosis from chronic HP.
- name: Hypersensitivity Pneumonitis from Home Mold Exposure
  disease_term:
    preferred_term: hypersensitivity pneumonitis
    term:
      id: MONDO:0017853
      label: hypersensitivity pneumonitis
  description: Non-avian hypersensitivity pneumonitis triggered by home mold exposure can present with similar ILD features.
  distinguishing_features:
  - Home mold exposure identified as culprit antigen
  - Similar ILD features without avian exposure history
  evidence:
  - reference: PMID:40338891
    reference_title: "Hypersensitivity pneumonitis associated with home mold exposure: A retrospective cohort analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Home mold exposure was identified as the culprit antigen in 54 of 231 hypersensitivity pneumonitis patients."
    explanation: The cohort documents HP driven by home mold exposure, supporting mold-related HP as a non-avian differential diagnosis.
environmental:
- name: Bird Antigen Exposure
  influences_mechanisms:
  - target: Exposure to Avian Proteins
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Keeping birds, or using feather products, delivers avian protein to the
      airway repeatedly over months to years, and it is the repetition rather
      than any single exposure that produces disease.
    evidence:
    - reference: PMID:39958101
      reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "immune-mediated interstitial lung disease (ILD) resulting from the repeated inhalation of avian proteins found in bird droppings, feathers, and serum."
      explanation: >-
        Defines the disease as resulting from repeated inhalation of avian
        proteins found in bird droppings, feathers and serum, the exposure
        this node represents.
  description: Exposure to bird proteins from bird breeding, feather products, or fertilizer with fowl droppings.
  exposure_term:
    preferred_term: exposure to animal waste material
    term:
      id: ECTO:7000098
      label: exposure to animal waste material
  evidence:
  - reference: PMID:33041192
    reference_title: "Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings."
    explanation: The abstract explicitly lists common avian antigen exposure sources.
  - reference: PMID:14503346
    reference_title: "[A case of acute bird fancier's lung caused by feather duvet]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She had raised two budgerigars for the last 15 years and had been using a feather duvet for one year."
    explanation: The case report documents direct bird exposure and feather product exposure associated with bird fancier's lung.
  - reference: PMID:1053441
    reference_title: "Pigeon breeders' disease--a prevalence study and review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among fifty-three Salt Lake City, Utah area pigeon fanciers, 21% were found to have the clinical picture of pigeon breeders' disease."
    explanation: Pigeon fancier exposure is directly tied to bird fancier's lung in this prevalence study.
  - reference: PMID:39958101
    reference_title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "immune-mediated interstitial lung disease (ILD) resulting from the repeated inhalation of avian proteins found in bird droppings, feathers, and serum."
    explanation: The case report explicitly identifies avian protein sources (droppings, feathers, serum) as exposure triggers.
  - reference: PMID:33318919
    reference_title: "Bird Fancier's lung: An underdiagnosed etiology of dyspnea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "triggered by exposure to highly antigenic avian proteins excreted in bird droppings and waxy proteins covering feathers of a variety of birds"
    explanation: The case report details avian protein sources in droppings and feathers as causative exposures.
  - reference: DOI:10.29262/ram.v72i4.1462
    reference_title: "&lt;b&gt;Domestic hypersensitivity pneumonitis caused by inadvertent exposure to feathers &lt;/b&gt;"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Objective: Case series of patients with domestic hypersensitivity pneumonitis, focusing on hidden avian exposures or other non-suspected antigens (feather comforters and pillows)."
    explanation: The case series highlights feather bedding as hidden avian exposure sources linked to HP.
clinical_trials:
- name: NCT02958917
  phase: PHASE_II
  status: TERMINATED
  description: Randomized, double-blind, placebo-controlled study evaluating pirfenidone in fibrotic hypersensitivity pneumonitis.
  target_phenotypes:
  - preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  - preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: clinicaltrials:NCT02958917
    reference_title: "A Randomized, Double-Blind, Placebo-Controlled, Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients are being offered participation in this pirfenidone trial because They have been diagnosed with fibrotic hypersensitivity pneumonitis (FHP), a type of interstitial lung disease (ILD)."
    explanation: The registry entry specifies the trial population and disease focus.
- name: NCT02496182
  phase: PHASE_II
  status: UNKNOWN
  description: Study evaluating addition of pirfenidone to prednisone and azathioprine in chronic hypersensitivity pneumonitis with pulmonary fibrosis.
  notes: ClinicalTrials.gov lists Phase 2 and Phase 3 for this study.
  target_phenotypes:
  - preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  - preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: clinicaltrials:NCT02496182
    reference_title: Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the investigators propose to evaluate the addition of Pirfenidone to the actual treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis."
    explanation: The registry summary outlines treatment strategy and target population.
- name: NCT04844359
  phase: NOT_APPLICABLE
  status: ACTIVE_NOT_RECRUITING
  description: Observational study developing and validating a prognostic blood transcriptomic signature in chronic hypersensitivity pneumonitis.
  target_phenotypes:
  - preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  - preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: clinicaltrials:NCT04844359
    reference_title: Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Up to 150 patients with hypersensitivity pneumonitis will be enrolled at 7 clinical centers across the United States. Patients will be followed for 24 months to determine if biomarkers in the blood can predict disease progression."
    explanation: The registry summary describes enrollment and biomarker-focused outcomes.
animal_models:
- species: Mus musculus
  description: Mouse model sensitized with pigeon serum and challenged intranasally to induce bird-related hypersensitivity pneumonitis.
  evidence:
  - reference: DOI:10.3390/ijms24032884
    reference_title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "On days −3 and −1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2)."
    explanation: The study describes a pigeon serum-induced mouse model of BRHP.
- species: Mus musculus
  description: Pigeon breeder's lung model generated by tracheal instillation of pigeon dropping extract protein powder.
  evidence:
  - reference: PMID:39844643
    reference_title: "Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder."
    explanation: The study establishes a pigeon breeder's lung mouse model using pigeon dropping extract.
datasets:
- accession: geo:GSE150910
  title: "RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung"
  description: >-
    Bulk RNA-seq of whole lung tissue from chronic hypersensitivity pneumonitis,
    idiopathic pulmonary fibrosis, and controls. The HP samples are not
    stratified by inciting antigen, so this is shared HP context rather than a
    BFL-specific cohort.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: lung tissue
    term:
      id: UBERON:0002048
      label: lung
    tissue_term:
      preferred_term: lung
      term:
        id: UBERON:0002048
        label: lung
  conditions:
  - hypersensitivity pneumonitis
  - idiopathic pulmonary fibrosis
  - normal lung
  publication: PMID:32602730
  evidence:
  - reference: PMID:32602730
    reference_title: "Chronic Hypersensitivity Pneumonitis, an Interstitial Lung Disease with Distinct Molecular Signatures."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transcriptome analysis of lung samples from CHP (n = 82), IPF (n = 103), and unaffected controls (n = 103) was conducted."
    explanation: The study reports bulk transcriptome profiling of lung samples from chronic HP, IPF, and controls, matching the dataset description.
  notes: >-
    GEO record includes HP, IPF, and control whole-lung RNA-seq samples; avian
    exposure status is not supplied at dataset level.
- accession: geo:GSE271789
  title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis"
  description: >-
    Single-cell and single-nucleus RNA-seq of PBMCs and BAL cells from fibrotic
    hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, and controls.
    The HP cohort is not stratified by inciting antigen.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_types:
  - preferred_term: peripheral blood mononuclear cell
    term:
      id: CL:2000001
      label: peripheral blood mononuclear cell
    cell_type_term:
      preferred_term: peripheral blood mononuclear cell
      term:
        id: CL:2000001
        label: peripheral blood mononuclear cell
  - preferred_term: bronchoalveolar lavage
    term:
      id: NCIT:C13195
      label: Bronchoalveolar Lavage Fluid
    tissue_term:
      preferred_term: lung
      term:
        id: UBERON:0002048
        label: lung
  conditions:
  - fibrotic hypersensitivity pneumonitis
  - idiopathic pulmonary fibrosis
  - healthy control
  publication: PMID:38924775
  evidence:
  - reference: PMID:38924775
    reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico."
    explanation: The abstract documents single-cell sequencing of PBMC and BAL cells from fibrotic HP, IPF, and controls, aligning with the dataset.
  notes: >-
    GEO record linked to the AJRCCM 2024 single-cell study profiling PBMC and
    BAL; it informs shared fibrotic-HP mechanisms rather than a proven
    avian-specific program.
discussions:
- discussion_id: interpretation_bfl_serology_exposure_not_causation
  prompt: >-
    How should positive bird-specific IgG or IgA be interpreted when other
    diagnostic domains are discordant?
  kind: INTERPRETATION
  status: OPEN
  attaches_to:
  - diagnosis#Bird antigen-specific IgG serology as exposure support
  rationale: >-
    Bird-specific antibodies document sensitization and likely exposure. They
    do not establish that the exposure caused the ILD, and test panels and
    thresholds are not standardized internationally. The entry therefore does
    not model positive serology as an independently diagnostic biomarker.
  evidence:
  - reference: PMID:32706311
    reference_title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It was emphasized that a positive serum IgG result does not mean that the
      exposure is the cause of the lung condition; it only indicates that the
      patient has likely been exposed to a potential cause of HP at some point
      in his or her life
    explanation: The guideline directly separates exposure evidence from disease causation.
- discussion_id: gap_bfl_antigen_stratified_fibrotic_mechanisms
  prompt: >-
    Which single-cell and profibrotic mechanisms demonstrated in pooled or
    non-avian HP are reproduced specifically in human avian-antigen disease?
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - pathophysiology#Classical Monocyte Enrichment
  - pathophysiology#MMP14-High Macrophage Profibrotic Activity
  rationale: >-
    The single-cell cohorts are not stratified by inciting antigen, while the
    MMP14 perturbation study uses a non-avian SR-antigen mouse model. These
    results are retained as partial shared-HP evidence, not as established
    bird-specific mechanisms.
  evidence:
  - reference: PMID:38924775
    reference_title: "Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Single-cell 5' RNA sequencing was conducted on peripheral blood
      mononuclear cells and BAL cells obtained from 45 patients with FHP, 63
      patients with idiopathic pulmonary fibrosis (IPF), 4 patients with
      nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects
      in the United States and Mexico.
    explanation: The cohort is defined at HP phenotype level without an avian-antigen subgroup.
  - reference: PMID:38218353
    reference_title: "MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag.
    explanation: The perturbation is performed in an SR-antigen rather than avian-antigen model.
- discussion_id: gap_bfl_genetic_susceptibility_specificity
  prompt: >-
    Do reported MUC5B and TOLLIP associations predict susceptibility or outcome
    specifically in bird-related HP rather than in pooled fibrotic HP?
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: >-
    The available association is for fibrotic HP and is non-causal. MUC5B and
    TOLLIP are therefore not represented as causal BFL genes; antigen-stratified
    replication and functional evidence would be needed.
  evidence:
  - reference: PMID:38309995
    reference_title: "Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP.
    explanation: The study reports association with pooled fibrotic HP, not causation or BFL specificity.
- discussion_id: gap_bfl_antifibrotic_efficacy
  prompt: >-
    What is the comparative efficacy of nintedanib and pirfenidone in
    progressive fibrotic BFL after avian-antigen removal?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - treatments#Nintedanib for Progressive Fibrosing Disease
  - treatments#Investigational Pirfenidone for Fibrotic HP
  rationale: >-
    INBUILD was not powered for the HP subgroup or stratified by avian exposure.
    The pirfenidone trial enrolled only 40 participants and was underpowered for
    its primary endpoint. BFL-specific comparative evidence remains absent.
  evidence:
  - reference: PMID:32145830
    reference_title: "Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The INBUILD trial was not designed or powered to provide evidence for a
      benefit of nintedanib in specific diagnostic subgroups.
    explanation: The trial authors explicitly limit diagnosis-specific inference.
  - reference: PMID:37028940
    reference_title: "Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The trial was underpowered to detect a difference in the primary end point.
    explanation: The pirfenidone trial authors explicitly identify inadequate power.
review_notes: >-
  This record is scoped to avian-antigen hypersensitivity pneumonitis rather
  than to all HP. The prior United Kingdom rate was removed because its source
  estimated overall domestic HP incidence, not BFL incidence. Modern
  nonfibrotic/fibrotic phenotypes are primary; recurrent and insidious chronic
  BFL are retained as historical bird-specific course patterns. General or
  pooled HP evidence is used only where a diagnostic, management, or shared
  fibrotic mechanism reasonably applies, and such extrapolation is labeled
  partial. The two GEO datasets are not antigen-stratified. MUC5B and TOLLIP
  associations are non-causal pooled-fibrotic-HP findings and are recorded as a
  knowledge gap rather than causal genes. Bird-specific IgG supports exposure
  but cannot diagnose BFL alone. Complete avian-antigen avoidance remains the
  management foundation; corticosteroid evidence is phenotype-dependent,
  nintedanib evidence comes from a broader progressive-fibrosing-ILD trial, and
  pirfenidone remains investigational. The FREQUENT dyspnea and cough bands use
  the guideline's qualitative "common" wording; frequency qualifiers are
  omitted for the remaining phenotypes because their evidence supports the
  associations but not quantitative or qualitative frequency bands.
references:
- reference: DOI:10.3390/ijms24032884
  title: Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
  findings: []
- reference: PMID:32706311
  title: Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.
  findings: []
- reference: PMID:39870058
  title: "Diagnosis and Treatment of Hypersensitivity Pneumonitis: S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology."
  findings: []
- reference: PMID:12839317
  title: "Clinical features of recurrent and insidious chronic bird fancier's lung."
  findings: []
- reference: PMID:1053441
  title: "Pigeon breeders' disease--a prevalence study and review."
  findings: []
- reference: PMID:21870048
  title: "Bird fancier's lung: a state-of-the-art review."
  findings: []
- reference: PMID:6761066
  title: Immunology of hypersensitivity pneumonitis.
  findings: []
- reference: PMID:32764620
  title: Hypersensitivity pneumonitis.
  findings: []
- reference: PMID:39958101
  title: "Advanced Imaging and Occupational History in the Diagnosis of Bird Fancier's Lung: A Case Report."
  findings: []
- reference: PMID:33318919
  title: "Bird Fancier's lung: An underdiagnosed etiology of dyspnea."
  findings: []
- reference: PMID:33041192
  title: Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®.
  findings: []
- reference: PMID:14503346
  title: "[A case of acute bird fancier's lung caused by feather duvet]."
  findings: []
- reference: PMID:11131880
  title: "[A misleading form of hypersensitivity pneumonitis]."
  findings: []
- reference: PMID:38924775
  title: Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
  findings: []
- reference: PMID:38218353
  title: MMP14(high) macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis.
  findings: []
- reference: PMID:37028940
  title: "Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety."
  findings: []
- reference: PMID:32145830
  title: "Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial."
  findings: []
- reference: PMID:24480143
  title: "Chronic hypersensitivity pneumonitis and pulmonary sarcoidosis: differentiation from usual interstitial pneumonia using high-resolution computed tomography."
  findings: []
- reference: PMID:38762468
  title: Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis.
  findings: []
- reference: PMID:40049235
  title: Anti-chicken and anti-pigeon immunoglobulin G testing in patients with bird-related fibrotic hypersensitivity pneumonitis.
  findings: []
- reference: PMID:33861992
  title: "Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report."
  findings: []
- reference: PMID:35779842
  title: Validation of inhalation challenge test and serum immunoglobulin G test for bird-related fibrotic hypersensitivity pneumonitis.
  findings: []
- reference: DOI:10.3390/jcm8010014
  title: "Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study"
  findings: []
- reference: DOI:10.1371/journal.pone.0273544
  title: Impact of number and type of identified antigen on transplant-free survival in hypersensitivity pneumonitis
  findings: []
- reference: PMID:27816444
  title: Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis.
  findings: []
- reference: clinicaltrials:NCT02958917
  title: A Randomized, Double-Blind, Placebo-Controlled, Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis
  findings: []
- reference: PMID:40338891
  title: "Hypersensitivity pneumonitis associated with home mold exposure: A retrospective cohort analysis."
  findings: []
- reference: DOI:10.29262/ram.v72i4.1462
  title: "&lt;b&gt;Domestic hypersensitivity pneumonitis caused by inadvertent exposure to feathers &lt;/b&gt;"
  findings: []
- reference: clinicaltrials:NCT02496182
  title: Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment
  findings: []
- reference: clinicaltrials:NCT04844359
  title: Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis
  findings: []
- reference: PMID:39844643
  title: "Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model."
  findings: []
- reference: PMID:32602730
  title: Chronic Hypersensitivity Pneumonitis, an Interstitial Lung Disease with Distinct Molecular Signatures.
  findings: []
- reference: PMID:38309995
  title: Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis.
  findings: []

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