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Bird Fancier's Lung

Respiratory Disease MONDO:0005668 Respiratory Disease Inflammatory Lung Disease

Immune-mediated interstitial lung disease caused by repeated inhalation of avian proteins, leading to inflammatory and sometimes fibrotic lung injury.

0
Mappings
0
Definitions
0
Inheritance
11
Pathophysiology
1
Histopathology
6
Phenotypes
2
Genes
4
Treatments
2
Subtypes
3
Differentials
2
Datasets
3
Trials
◆

Subtypes

2
Recurrent chronic bird fancier's lung
Chronic BFL with recurrent acute episodes that progress to interstitial pulmonary fibrosis.
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
Chronic BFL with slowly progressive respiratory disease without a history of acute episodes.
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.
⚙

Pathophysiology

11
Exposure to Avian Proteins
Repeated inhalation of avian proteins from bird droppings, feathers, or serum triggers bird-related hypersensitivity pneumonitis.
lung link
Show evidence (3 references)
DOI:10.3390/ijms24032884 SUPPORT Model Organism
"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 link macrophage link dendritic cell link
lung link
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 link macrophage link dendritic cell link alveolar macrophage link
lung link
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 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 link
T cell activation link
lung link
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.
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 link
B cell activation link antigen processing and presentation link
lung link
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.
Species-Specific Bird Antigen Panels
Diagnostic panels for bird-related hypersensitivity pneumonitis use antigens from pigeon, parrot, and budgerigar species.
Show evidence (1 reference)
PMID:33041192 SUPPORT Human Clinical
"We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients."
The study explicitly lists pigeon, parrot, and budgerigar antigens as the species used in standardized antibody testing for bird-related HP.
Classical Monocyte Enrichment
Fibrotic hypersensitivity pneumonitis shows elevated classical monocytes enriched for CCL3hi/CCL4hi and S100Ahi states.
monocyte link
chemokine-mediated signaling pathway link
lung link
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 classical monocyte states in fibrotic HP.
Monocyte-to-SPP1hi Macrophage Differentiation
Specific classical monocyte states differentiate into SPP1hi lung macrophages associated with fibrosis.
monocyte link macrophage link
lung link
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 fibrotic HP.
Cytotoxic T Cell Program with Profibrotic Signaling
Fibrotic hypersensitivity pneumonitis features GZMhi cytotoxic T cells with transcriptional programs implicating TGFβ, TNFα, and NFκB pathways.
T cell link
T cell activation link
lung link
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
MMP14-high macrophages with an M2-like phenotype promote fibroblast-to-myofibroblast transition in hypersensitivity pneumonitis models, contributing to fibrotic remodeling.
alveolar macrophage link
extracellular matrix organization link
alveolus of lung link
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 study identifies a macrophage subset driving fibroblast-to-myofibroblast transition, a key fibrotic remodeling process.
TLR2 and NF-κB Regulation of MMP14 and Exosome Secretion
TLR2 and NF-κB signaling regulate MMP14 expression and macrophage exosome secretion in antigen-stimulated hypersensitivity pneumonitis models.
macrophage link
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

1
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.
●

Phenotypes

6
Metabolism(1) Respiratory(4) Constitutional(1)
Metabolism 1
Fever OCCASIONAL Fever (HP:0001945)
Show evidence (1 reference)
PMID:14503346 PARTIAL 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 Dyspnea (HP:0002094)
Show evidence (2 references)
PMID:14503346 PARTIAL 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 PARTIAL 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.
Cough FREQUENT Cough (HP:0012735)
Show evidence (1 reference)
PMID:14503346 PARTIAL 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.
Pulmonary Fibrosis OCCASIONAL 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 PARTIAL 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 PARTIAL 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 OCCASIONAL Hypoxemia (HP:0012418)
Show evidence (1 reference)
PMID:11131880 PARTIAL 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 OCCASIONAL Fatigue (HP:0012378)
Show evidence (1 reference)
PMID:6761066 SUPPORT Human Clinical
"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.
🧬

Genetic Associations

2
MUC5B (Susceptibility risk in fibrotic hypersensitivity pneumonitis (non-causal))
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 case-control study reports MUC5B association with susceptibility.
TOLLIP (Susceptibility risk in fibrotic hypersensitivity pneumonitis (non-causal))
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 identifies TOLLIP variants associated with fibrotic HP.
💊

Treatments

4
Prednisone and Azathioprine MAXO:0000640
Drug: prednisone ↗ azathioprine ↗
Glucocorticoid therapy with prednisone, sometimes combined with azathioprine, has been used in chronic hypersensitivity pneumonitis.
Show evidence (2 references)
clinicaltrials:NCT02496182 SUPPORT Human Clinical
"Actually HP has been treated with Prednisone and occasionally with Azathioprine, but unfortunately the treatment with these drugs have not an effective result to treat the interstitial fibrosis."
The trial summary notes existing use of prednisone and azathioprine in chronic hypersensitivity pneumonitis.
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."
The case report documents corticosteroid treatment for BFL.
Mycophenolate Mofetil or Azathioprine MAXO:0000058
Drug: mycophenolate mofetil ↗ azathioprine ↗
Immunosuppressive pharmacotherapy with mycophenolate mofetil or azathioprine has been used in chronic hypersensitivity pneumonitis and associated with improved DLCO.
Show evidence (1 reference)
PMID:27816444 PARTIAL Human Clinical
"We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP."
The study explicitly evaluates MMF and azathioprine therapy in chronic hypersensitivity pneumonitis.
Pirfenidone MAXO:0000058
Drug: pirfenidone ↗
Antifibrotic pharmacotherapy evaluated for fibrotic hypersensitivity pneumonitis.
Show evidence (2 references)
PMID:37028940 SUPPORT Human Clinical
"Pirfenidone was found to be safe and improved PFS in patients with FHP."
The randomized trial reports improved progression-free survival with pirfenidone in fibrotic hypersensitivity pneumonitis.
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 specifies pirfenidone as the studied treatment in fibrotic hypersensitivity pneumonitis.
Nintedanib MAXO:0000058
Drug: nintedanib ↗
Antifibrotic therapy shown to reduce the rate of FVC decline in progressive fibrosing ILD, including hypersensitivity pneumonitis subgroups.
Show evidence (1 reference)
PMID:32145830 SUPPORT Human Clinical
"The effect of nintedanib versus placebo on reducing the rate of FVC decline (mL/year) was consistent across the five subgroups by ILD diagnosis"
The INBUILD subgroup analysis supports nintedanib for progressive fibrosing ILD, including the hypersensitivity pneumonitis subgroup.
🌍

Environmental Factors

1
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
🔬

Biochemical Markers

1
Bird antigen-specific IgG/IgA antibodies (Positive)
Show evidence (3 references)
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 antibodies are reported in affected patients.
PMID:38762468 PARTIAL 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.
🔀

Differential Diagnoses

3

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

Idiopathic Pulmonary Fibrosis Not Yet Curated 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 Not Yet Curated 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

2
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 control samples.
human BULK RNA SEQ
lung tissue
Conditions: hypersensitivity pneumonitis idiopathic pulmonary fibrosis normal lung
PMID:32602730
GEO record includes HP, IPF, and control whole-lung RNA-seq samples.
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.
human SINGLE CELL RNA SEQ
peripheral blood mononuclear cell link bronchoalveolar lavage
Conditions: fibrotic hypersensitivity pneumonitis idiopathic pulmonary fibrosis healthy control
PMID:38924775
GEO record linked to AJRCCM 2024 single-cell study profiling PBMC and BAL.
Show evidence (1 reference)
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 abstract documents single-cell sequencing of PBMC and BAL cells from fibrotic HP, IPF, and controls, aligning with the dataset.
🔬

Clinical Trials

3
NCT02958917 PHASE_II TERMINATED
Randomized, double-blind, placebo-controlled study evaluating pirfenidone in fibrotic hypersensitivity pneumonitis.
Target Phenotypes: Dyspnea ↗ Pulmonary fibrosis ↗
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 ↗ Cough ↗
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 ↗ Dyspnea ↗
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.
{ }

Source YAML

click to show 
name: Bird Fancier's Lung
creation_date: '2026-01-30T23:42:47Z'
updated_date: '2026-01-31T14:57:37Z'
category: Respiratory Disease
parents:
- Respiratory Disease
- Inflammatory Lung Disease
has_subtypes:
- name: Recurrent chronic bird fancier's lung
  description: Chronic BFL with recurrent acute episodes that progress to interstitial pulmonary fibrosis.
  evidence:
  - reference: PMID:12839317
    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: Chronic BFL with slowly progressive respiratory disease without a history of acute episodes.
  evidence:
  - reference: PMID:12839317
    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: Immune-mediated interstitial lung disease caused by repeated inhalation of avian proteins, leading to inflammatory and sometimes fibrotic lung injury.
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
prevalence:
- population: United Kingdom
  percentage: 0.001
  notes: Reported overall annual incidence of hypersensitivity pneumonitis in a British study (approximately 1 per 100,000 per year).
  evidence:
  - reference: PMID:23101639
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Domestic hypersensitivity pneumonitis (HP) cases are relatively widespread, with an overall annual incidence of approximately 1/100,000 reported in a British study covering several million patients."
    explanation: The review reports a UK annual incidence estimate that can be used as a population-level rate for HP including bird fancier's lung.
epidemiology:
- name: High prevalence among pigeon fanciers
  description: Pigeon fanciers have a high prevalence of bird fancier's lung in regional cohort studies.
  evidence:
  - reference: PMID:1053441
    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 documents a high prevalence among 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
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    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
  notes: Acute hypersensitivity pneumonitis presents within hours after heavy antigen exposure.
  evidence:
  - reference: PMID:6761066
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    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
  notes: Chronic disease shows gradual symptom onset and can progress to pulmonary fibrosis.
  evidence:
  - reference: PMID:6761066
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    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.
stages:
- name: Acute/Inflammatory
  description: Acute hypersensitivity pneumonitis with rapid symptom onset after high-level antigen exposure.
  evidence:
  - reference: PMID:6761066
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Symptoms usually begin 4 to 6 hr after exposure to large quantities of causative organic dust."
    explanation: Rapid symptom onset is characteristic of acute disease.
- name: Chronic/Fibrotic
  description: Chronic hypersensitivity pneumonitis with gradual onset and risk of pulmonary fibrosis.
  evidence:
  - reference: PMID:6761066
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    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 describes chronic progression with fibrotic outcomes.
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
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    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
    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
    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.
- 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
    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.
- 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
    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.
- 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
    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.
- 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
    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.
- name: Species-Specific Bird Antigen Panels
  description: Diagnostic panels for bird-related hypersensitivity pneumonitis use antigens from pigeon, parrot, and budgerigar species.
  triggers:
  - preferred_term: pigeon
    term:
      id: NCBITaxon:8932
      label: Columba livia
  - preferred_term: parrot
    term:
      id: NCBITaxon:9223
      label: Psittaciformes
  - preferred_term: budgerigar
    term:
      id: NCBITaxon:13146
      label: Melopsittacus undulatus
  evidence:
  - reference: PMID:33041192
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients."
    explanation: The study explicitly lists pigeon, parrot, and budgerigar antigens as the species used in standardized antibody testing for bird-related HP.
- name: Classical Monocyte Enrichment
  description: Fibrotic hypersensitivity pneumonitis shows elevated classical monocytes enriched for CCL3hi/CCL4hi and S100Ahi states.
  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
    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 classical monocyte states in fibrotic HP.
- name: Monocyte-to-SPP1hi Macrophage Differentiation
  description: Specific classical monocyte states differentiate into SPP1hi lung macrophages associated with fibrosis.
  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
    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 fibrotic HP.
- name: Cytotoxic T Cell Program with Profibrotic Signaling
  description: Fibrotic hypersensitivity pneumonitis features GZMhi cytotoxic T cells with transcriptional programs implicating TGFβ, TNFα, and NFκB pathways.
  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
    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.
- name: MMP14-High Macrophage Profibrotic Activity
  description: MMP14-high macrophages with an M2-like phenotype promote fibroblast-to-myofibroblast transition in hypersensitivity pneumonitis models, contributing to fibrotic remodeling.
  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
    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 study identifies a macrophage subset driving fibroblast-to-myofibroblast transition, a key fibrotic remodeling process.
- name: TLR2 and NF-κB Regulation of MMP14 and Exosome Secretion
  description: TLR2 and NF-κB signaling regulate MMP14 expression and macrophage exosome secretion in antigen-stimulated hypersensitivity pneumonitis models.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  evidence:
  - reference: PMID:38218353
    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.
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
    supports: PARTIAL
    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
    supports: PARTIAL
    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.
- 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
    supports: PARTIAL
    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.
- category: Respiratory
  name: Pulmonary Fibrosis
  frequency: OCCASIONAL
  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
    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
    supports: PARTIAL
    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
    supports: PARTIAL
    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
    supports: PARTIAL
    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
  frequency: OCCASIONAL
  description: Reduced blood oxygenation during active disease.
  phenotype_term:
    preferred_term: Hypoxemia
    term:
      id: HP:0012418
      label: Hypoxemia
  evidence:
  - reference: PMID:11131880
    supports: PARTIAL
    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
  frequency: OCCASIONAL
  description: Systemic fatigue during symptomatic episodes.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:6761066
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    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
  frequency: OCCASIONAL
  description: Flu-like systemic symptoms during acute exposure episodes.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:14503346
    supports: PARTIAL
    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
    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.
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
    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
    supports: PARTIAL
    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
    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.
genetic:
- name: MUC5B
  association: Susceptibility risk in fibrotic hypersensitivity pneumonitis (non-causal)
  gene_term:
    preferred_term: MUC5B
    term:
      id: hgnc:7516
      label: MUC5B
  evidence:
  - reference: PMID:38309995
    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 case-control study reports MUC5B association with susceptibility.
- name: TOLLIP
  association: Susceptibility risk in fibrotic hypersensitivity pneumonitis (non-causal)
  gene_term:
    preferred_term: TOLLIP
    term:
      id: hgnc:16476
      label: TOLLIP
  evidence:
  - reference: PMID:38309995
    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 identifies TOLLIP variants associated with fibrotic HP.
diagnosis:
- name: Bronchoalveolar lavage lymphocytosis
  description: BAL shows a marked increase in lymphocytes in bird fancier's lung.
  evidence:
  - reference: PMID:14503346
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Bronchoalveolar lavage (BAL) revealed a marked increase in lymphocytes"
    explanation: The case report documents BAL lymphocytosis as a diagnostic finding.
- name: High-resolution computed tomography pattern
  description: HRCT shows centrilobular small nodules and lobular areas of decreased attenuation in chronic hypersensitivity pneumonitis.
  evidence:
  - reference: PMID:24480143
    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
    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: Bird antigen-specific IgG/IgA serology
  description: Elevated bird-specific IgG/IgA supports exposure attribution.
  evidence:
  - reference: PMID:33041192
    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 is a diagnostic serologic marker.
  - reference: PMID:38762468
    supports: PARTIAL
    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 IgG testing against pigeon serum supports diagnostic attribution to avian antigens.
  - reference: PMID:40049235
    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 by ELISA supports diagnostic testing for bird-related fibrotic HP.
- name: Inhalation challenge test
  description: Inhalation challenge testing is a sensitive diagnostic tool for bird-related fibrotic hypersensitivity pneumonitis.
  evidence:
  - reference: PMID:35779842
    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 study reports higher sensitivity for inhalation challenge testing compared to serology.
- name: Occupational and exposure history
  description: Detailed occupational or avian exposure history is critical for diagnosing bird fancier's lung.
  evidence:
  - reference: PMID:39958101
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "A thorough occupational history uncovered significant avian antigen exposure, and a family history suggested genetic susceptibility."
    explanation: The case report emphasizes occupational history to identify avian antigen exposure.
treatments:
- name: Prednisone and Azathioprine
  description: Glucocorticoid therapy with prednisone, sometimes combined with azathioprine, has been used in chronic hypersensitivity pneumonitis.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: MAXO:0000640
      label: corticosteroid agent therapy
    therapeutic_agent:
    - preferred_term: prednisone
      term:
        id: CHEBI:8382
        label: prednisone
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  evidence:
  - reference: clinicaltrials:NCT02496182
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Actually HP has been treated with Prednisone and occasionally with Azathioprine, but unfortunately the treatment with these drugs have not an effective result to treat the interstitial fibrosis."
    explanation: The trial summary notes existing use of prednisone and azathioprine in chronic hypersensitivity pneumonitis.
  - reference: PMID:39958101
    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: The case report documents corticosteroid treatment for BFL.
- name: Mycophenolate Mofetil or Azathioprine
  description: Immunosuppressive pharmacotherapy with mycophenolate mofetil or azathioprine has been used in chronic hypersensitivity pneumonitis and associated with improved DLCO.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  evidence:
  - reference: PMID:27816444
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP."
    explanation: The study explicitly evaluates MMF and azathioprine therapy in chronic hypersensitivity pneumonitis.
- name: Pirfenidone
  description: Antifibrotic pharmacotherapy evaluated for fibrotic hypersensitivity pneumonitis.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: pirfenidone
      term:
        id: CHEBI:32016
        label: pirfenidone
  evidence:
  - reference: PMID:37028940
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pirfenidone was found to be safe and improved PFS in patients with FHP."
    explanation: The randomized trial reports improved progression-free survival with pirfenidone in fibrotic hypersensitivity pneumonitis.
  - reference: clinicaltrials:NCT02958917
    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 specifies pirfenidone as the studied treatment in fibrotic hypersensitivity pneumonitis.
- name: Nintedanib
  description: Antifibrotic therapy shown to reduce the rate of FVC decline in progressive fibrosing ILD, including hypersensitivity pneumonitis subgroups.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: nintedanib
      term:
        id: CHEBI:85164
        label: nintedanib
  evidence:
  - reference: PMID:32145830
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The effect of nintedanib versus placebo on reducing the rate of FVC decline (mL/year) was consistent across the five subgroups by ILD diagnosis"
    explanation: The INBUILD subgroup analysis supports nintedanib for progressive fibrosing ILD, including the hypersensitivity pneumonitis subgroup.
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
    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
    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
    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
  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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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 control samples.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: lung tissue
    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
    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.
- 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.
  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
    cell_type_term:
      preferred_term: peripheral blood mononuclear cell
      term:
        id: CL:2000001
        label: peripheral blood mononuclear cell
  - preferred_term: bronchoalveolar lavage
    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
    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 AJRCCM 2024 single-cell study profiling PBMC and BAL.