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pulm.hypersensitivity-pneumonitis.v1PRODUCTION
pulm.hypersensitivity-pneumonitis.v1

Hypersensitivity pneumonitis (acute + chronic-fibrotic)

pulmonologysubacutechronicadult
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Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Adult subacute/chronic immune-mediated antigen-driven ILD — establish the NONFIBROTIC-vs-FIBROTIC fork (the dominant prognostic + therapeutic axis) and adjudicate via the ATS/JRS/ALAT 2020 diagnostic-confidence framework at MDD (pulm + thoracic radiology + pathology). Scope excludes IPF/UIP, NSIP, sarcoidosis, CTD-ILD, drug-induced ILD, infection (differential-as-data)

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HP confidence category assigned at MDD

Patient inputs (18)

HP spans wide age range; fibrotic HP older; transplant candidacy (ATS/JRS/ALAT 2020)

Structured exposure questionnaire (birds/mold/farm/hot-tub/MWF/isocyanate, temporal symptom-exposure relationship) — first domain of the ATS/JRS/ALAT 2020 confidence framework; antigen identification is the highest-leverage intervention

Occupation + hobby + home environment for avoidable-antigen branch + occupational-medicine referral (ATS/JRS/ALAT 2020)

Resting + ambulatory hypoxemia drives O2 prescription; acute severe HP respiratory-failure trigger (ATS/JRS/ALAT 2020)

Drug-induced ILD screen (amiodarone, nitrofurantoin, minocycline, MTX, ICI); CYP/anticoagulant interactions for nintedanib (ATS/JRS/ALAT 2020 differential; DailyMed)

Serum IgG / specific precipitins to suspected antigens — supports antigen domain of ATS/JRS/ALAT 2020 confidence framework (suggested test)

Exclude CTD-ILD before labelling HP — ANA/RF/CCP/Scl-70/Jo-1/MDA5/Ro52 (ATS/JRS/ALAT 2020 differential)

Baseline before immunosuppression/antifibrotic; AZA myelosuppression surveillance (DailyMed labels)

AZA/MMF/nintedanib hepatotoxicity baseline + serial LFT; renal dosing (DailyMed labels)

HRCT typical/compatible/indeterminate pattern + fibrosis grading — second domain of ATS/JRS/ALAT 2020 framework; three-density sign / mosaic air-trapping characteristic

FVC + DLCO baseline + serial — restrictive (or mixed for avian) physiology; FVC trend drives progression/antifibrotic/transplant (ATS/JRS/ALAT 2020)

Functional capacity + exertional desaturation; prognostic + O2 prescription (ATS/JRS/ALAT 2020)

BAL lymphocyte differential — third domain; pooled 42.8% in CHP vs 10.0% IPF; >20% sens 68.1%/spec 64.8% (Adderley 2020 PMID 32265306); recommended in nonfibrotic, suggested in fibrotic (ATS/JRS/ALAT 2020)

Transbronchial / cryobiopsy / surgical lung biopsy by phenotype + residual diagnostic uncertainty per ATS/JRS/ALAT 2020 algorithm

Females more likely to manifest fibrotic-HP CT features (mosaic attenuation aOR 0.27 in males; Copeland/Salisbury 2022 PMID 35877079)

Smoking paradoxically lowers HP incidence but is associated with worse fibrotic prognosis/honeycombing (Copeland/Salisbury 2022 PMID 35877079)

MMF is teratogenic (contraindicated in pregnancy) → azathioprine acceptable; antifibrotic contraindicated; minimise corticosteroid (special-pop branch)

TPMT/NUDT15 activity before azathioprine — myelosuppression risk genotyping (AZA DailyMed label)

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Severity triggers (9)

9 need judgement
  • informationallife_threateningacute_severe_hp_respiratory_failure
    Acute severe HP with hypoxemic respiratory failure after heavy antigen exposure — high fever + diffuse infiltrate + hypoxemia closely mimicking infection
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningae_like_fibrotic_hp_deterioration
    Acute-exacerbation-like deterioration of fibrotic HP — acute worsening dyspnea + new bilateral GGO/consolidation on background fibrosis not fully explained by HF/PE/infection (IPF-AE Collard-type definition applied to fibrotic HP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprogressive_fibrotic_hp_phenotype
    Progressive fibrotic HP — ≥10% relative FVC decline (or worsening fibrosis/symptoms) over 6–12 mo despite antigen avoidance ± immunosuppression
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_hypoxemia_resting
    Resting SpO2 ≤88% on room air in fibrotic HP
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremycophenolate_in_pregnancy
    Patient on (or candidate for) mycophenolate who is pregnant or of childbearing potential without effective contraception
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverefibrotic_hp_poor_prognosis_modifiers
    Fibrotic HP with poor-prognosis radiologic/histologic modifiers — UIP-like pattern, extensive fibrosis, severe traction bronchiectasis, honeycombing, high fibroblastic-foci profusion
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateunidentified_antigen_worse_prognosis
    No culprit antigen identified after structured questionnaire ± serum IgG ± environmental investigation
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateimmunosuppressant_or_antifibrotic_toxicity
    AZA/MMF myelosuppression or hepatotoxicity, or nintedanib AST/ALT >3× ULN / severe GI / bleeding
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatedifferential_hp_confidence_categories
    Is it HP, and how confident? §5.5.2 ATS/JRS/ALAT 2020 (PMID 32706311) confidence framework as DATA — confidence is a joint function of (1) antigen identification ± serum IgG, (2) HRCT pattern (typical/compatible/indeterminate — mosaic attenuation + air-trapping + three-density/headcheese sign + centrilobular GGO nodules; fibrotic adds reticulation/traction bronchiectasis/honeycombing), (3) BAL lymphocytosis ± histopathology → DEFINITE ≥90% / HIGH 80–89% / MODERATE 70–79% / LOW 51–69% / not-excluded, adjudicated at MDD. Discriminators with test characteristics: IPF/UIP (no antigen, BAL lymphocyte ~10%, UIP HRCT, older male → route pulm.idiopathic_pulmonary_fibrosis.v1); NSIP (younger, GGO-predominant, BAL lymphocytosis overlaps, steroid-responsive — no on-disk dossier); sarcoidosis (perilymphatic nodules + hilar adenopathy, BAL CD4/CD8 >3.5 → route pulm.sarcoidosis.v1); CTD-ILD (+autoantibodies + extrathoracic features — no on-disk dossier, rheum MDD); drug-induced ILD (temporal culprit amiodarone/nitrofurantoin/minocycline/MTX/ICI, reversible if stopped — no on-disk dossier); infection (acute-HP mimic → route pulm.cap.core.v1). BAL lymphocyte >20% sens 68.1%/spec 64.8%; >30–40% raises specificity, lowers sensitivity (Adderley 2020 PMID 32265306); HP six-predictor model ~95% accuracy (Watts/Grammer 2019 PMID 31690386)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

HP antigen-avoidance + anti-inflammatory + steroid-sparing + antifibrotic — ATS/JRS/ALAT 2020
axis: hp_avoidance_antiinflammatory_antifibrotic
Selected axis "HP antigen-avoidance + anti-inflammatory + steroid-sparing + antifibrotic — ATS/JRS/ALAT 2020" by default fallback (first axis)
  • antigen identification + complete avoidance/remediation
    first line
    environmental_intervention
    identify culprit antigen (structured questionnaire ± serum IgG) then COMPLETE removal/remediation — remove birds/feather/down bedding, mold remediation, stop hot-tub/humidifier, MWF/isocyanate engineering controls or work restriction • n/a • permanent; verified at every visit
    triggers: HP_diagnosed_any_confidence_category, identified_avoidable_antigen
    ATS/JRS/ALAT 2020 (PMID 32706311) — antigen identification + avoidance is the CORNERSTONE and the only intervention with a survival signal; unidentified antigen confers worse prognosis. Co-manage with occupational/environmental medicine; re-exposure = treatment failure
  • prednisone
    first line
    systemic_corticosteroid
    0.5–1 mg/kg/day PO (commonly ~40–60 mg/day) for acute/inflammatory nonfibrotic HP; taper over weeks–months guided by symptoms/PFT/HRCT response (taper documented here — `taper_plan` field does NOT exist in _types.ts) • PO • once daily then tapered (max: individualised; minimise cumulative exposure)
    triggers: nonfibrotic_inflammatory_HP, symptomatic_or_functionally_impaired, incomplete_response_to_avoidance_alone
    ATS/JRS/ALAT 2020 — corticosteroid gives acute symptomatic/functional benefit in inflammatory HP but limited long-term disease modification; avoidance remains primary. Taper (not abrupt stop): consolidate 4–8 wk at induction dose then step down over weeks–months with symptom/PFT/HRCT reassessment; monitor glucose/BP/bone/infection during taper
    rxcui 8640
  • methylprednisolone
    rescue
    systemic_corticosteroid
    500–1000 mg IV daily ×3 (pulse) then transition to oral prednisone taper for acute severe HP respiratory failure / AE-like fibrotic deterioration • IV • pulse ×3 then oral taper
    triggers: acute_severe_HP_respiratory_failure, AE_like_fibrotic_HP_after_infection_PE_HF_excluded
    Acute severe HP / AE-like fibrotic-HP deterioration — high-dose/pulse corticosteroid is common practice with limited controlled evidence; exclude and treat infection/PE/HF first; align ICU/ECMO escalation with transplant candidacy + goals of care (ATS/JRS/ALAT 2020; AE concept from Collard-type ILD-AE definition applied to fibrotic HP)
    rxcui 6902
  • mycophenolate mofetil
    second line
    antimetabolite_immunosuppressant
    500 mg PO BID titrating to 1000–1500 mg BID as tolerated • PO • BID (max: ~3000 mg/day)
    triggers: progressive_inflammatory_or_chronic_HP, corticosteroid_dependent_or_intolerant, steroid_sparing_required
    ATS/JRS/ALAT 2020 — steroid-sparing immunosuppression for progressive inflammatory/chronic HP unresponsive to avoidance ± corticosteroid; stabilises lung function in observational cohorts. RxCUI 68149 (mycophenolate mofetil ingredient) NOT independently re-verified via RxNav this pass — see .depth.md §RxCUI-audit (verify-flag). CONTRAINDICATED in pregnancy (teratogen) → use azathioprine branch
    rxcui 68149
  • azathioprine
    second line
    antimetabolite_immunosuppressant
    1 mg/kg/day PO, titrate to ~2–2.5 mg/kg/day (TPMT/NUDT15-informed) • PO • once daily (max: ~2.5 mg/kg/day)
    triggers: progressive_inflammatory_or_chronic_HP, mycophenolate_intolerant_or_pregnancy, BAL_lymphocytosis_present
    ATS/JRS/ALAT 2020 — alternative steroid-sparing agent; ~61% AZA-responder rate at 12 mo and BAL lymphocytosis predicts favourable response (OR 1.051, 95% CI 1.015–1.089; Raimundo 2021 PMID 33621590). Check TPMT/NUDT15 before start; CBC + LFT surveillance. RxCUI 1256 (azathioprine ingredient) NOT independently re-verified via RxNav this pass — see .depth.md §RxCUI-audit (verify-flag)
    rxcui 1256
  • nintedanib
    add on
    antifibrotic_intracellular_TKI
    150 mg PO BID (100 mg BID if hepatic impairment / poor tolerance) • PO • BID WITH FOOD (max: 300 mg/day)
    triggers: progressive_fibrotic_HP_despite_avoidance_and_immunosuppression, progressive_pulmonary_fibrosis_phenotype
    INBUILD HP subgroup (Wells Lancet Respir Med 2020 PMID 32145830): chronic-HP subgroup nintedanib vs placebo FVC-decline difference +73.1 mL/yr (95% CI -8.6 to 154.8); overall INBUILD progressive-fibrosing ILD annual FVC -80.8 vs -187.8 mL (Δ ~107 mL/yr; Flaherty NEJM 2019 PMID 31566307). RxCUI 1592737 confirmed correct in sibling pulm.idiopathic_pulmonary_fibrosis.v1 §RxCUI-audit 2026-05-16. Diarrhoea most common ADR; hepatotoxicity; bleeding/arterial-thromboembolic caution; CYP3A4/P-gp substrate; AVOID Child-Pugh B/C, reduce to 100 mg BID Child-Pugh A
    rxcui 1592737
  • oxygen
    comorbidity specific
    oxygen
    titrate to resting SpO2 ≥90%; ambulatory O2 for exertional desaturation • inhaled • continuous if resting SpO2 ≤88%
    triggers: resting_SpO2_le_88, exertional_desaturation_lt_88_on_6MWT
    ATS/JRS/ALAT 2020 supportive — LTOT for resting hypoxemia; ambulatory O2 for isolated exertional desaturation in fibrotic HP
    rxcui 7806
  • pulmonary rehabilitation
    comorbidity specific
    rehabilitation
    structured exercise + education program • n/a • program course; maintenance thereafter
    triggers: symptomatic_HP, exertional_limitation
    Supportive — improves 6MWD, dyspnea, QoL in fibrotic ILD including fibrotic HP (extrapolated from ILD rehab evidence)
  • lung transplant referral
    comorbidity specific
    definitive_therapy
    early referral for progressive fibrotic HP without absolute contraindication • n/a • one-time referral + ongoing co-management
    triggers: progressive_fibrotic_HP, FVC_decline_ge_10pct_6_12mo_despite_therapy, DLCO_lt_40, resting_or_exertional_hypoxemia
    Lung transplant is the only disease-modifying option for end-stage progressive fibrotic HP; refer early when progressive despite avoidance + immunosuppression ± antifibrotic (ISHLT candidate-selection principles; ATS/JRS/ALAT 2020)
  • nonfibrotic vs fibrotic phenotype routing (axis selector)
    comorbidity specific
    phenotype_router
    nonfibrotic → avoidance + corticosteroid ± steroid-sparing (often reversible); fibrotic → avoidance + (immunosuppression if inflammatory component) + ANTIFIBROTIC if progressive + transplant/palliative • n/a • at diagnosis + re-evaluated on progression
    triggers: nonfibrotic_HP, fibrotic_HP
    Special-pop branch: the ATS/JRS/ALAT 2020 nonfibrotic-vs-fibrotic dichotomy is the dominant therapeutic fork — nonfibrotic is inflammatory/often reversible (anti-inflammatory axis); fibrotic is UIP-like/progressive (antifibrotic axis, prognosis approaching IPF). Fibroblastic-foci profusion HR 2.36 (Chiba 2016 PMID 26836921) + traction-bronchiectasis HR 1.10 (Walsh 2012 PMID 22466512) gate aggressiveness
  • occupational / avoidable-antigen remediation + work restriction
    comorbidity specific
    occupational_intervention
    environmental remediation + occupational-medicine referral; respirator/engineering controls; job modification or removal if remediation insufficient (farmer's lung, MWF, isocyanate, bird-handler) • n/a • until verified antigen-free
    triggers: occupational_or_avoidable_antigen_identified
    Special-pop branch: occupational/avoidable antigen — the highest-leverage actionable scenario; complete avoidance can arrest or reverse nonfibrotic HP. Verify remediation success at follow-up; partial avoidance often fails
  • unidentified-antigen strategy (empiric remediation + lower IS/antifibrotic threshold)
    comorbidity specific
    risk_modified_strategy
    broad empiric environmental remediation (avian/mold/humidifier sweep) + lower threshold for steroid-sparing immunosuppression / antifibrotic + tighter FVC/DLCO surveillance • n/a • continuous
    triggers: no_culprit_antigen_identified
    Special-pop branch: unidentified antigen confers WORSE survival (ATS/JRS/ALAT 2020) — cannot remove what is not found, so escalate pharmacologic disease modification earlier and surveil more closely
  • azathioprine (pregnancy — preferred steroid-sparing agent; AVOID mycophenolate)
    contraindication substitute
    antimetabolite_immunosuppressant
    1 mg/kg/day titrating per tolerance (TPMT/NUDT15-informed); minimise corticosteroid; antifibrotic CONTRAINDICATED in pregnancy • PO • once daily
    triggers: pregnancy_and_steroid_sparing_required
    Special-pop branch: pregnancy — mycophenolate is teratogenic (contraindicated); azathioprine is the preferred steroid-sparing agent if immunosuppression needed; nintedanib contraindicated in pregnancy; minimise corticosteroid dose; co-manage with maternal-fetal medicine. RxCUI 1256 carries the same verify-flag (see .depth.md §RxCUI-audit)
    rxcui 1256
  • nintedanib 100 mg BID (hepatic impairment — Child-Pugh A; AVOID Child-Pugh B/C) / IS renal-hepatic dose-modify
    contraindication substitute
    antifibrotic_intracellular_TKI
    100 mg PO BID (reduced) for Child-Pugh A; AZA/MMF dose-modify and intensify CBC/LFT in hepatic/renal impairment • PO • BID with food
    triggers: Child_Pugh_A_hepatic_impairment, renal_or_hepatic_impairment_on_immunosuppression
    Special-pop branch: hepatic/renal impairment — nintedanib reduce to 100 mg BID Child-Pugh A, NOT recommended Child-Pugh B/C (DailyMed label); azathioprine + mycophenolate require dose modification and intensified marrow/hepatic surveillance in hepatic/renal impairment
    rxcui 1592737

outpatient playbook — drug actions (4)

  1. 1. antigen identification + complete avoidance/remediation
    remove/remediate culprit (birds/down, mold, hot tub, MWF, isocyanate) • n/a • permanent
    trigger: HP diagnosed (any confidence category)
    Cornerstone; only intervention with a survival signal (ATS/JRS/ALAT 2020 PMID 32706311)
  2. 2. prednisone (nonfibrotic/inflammatory)
    0.5–1 mg/kg/day then taper over weeks–months • PO • daily then tapered
    trigger: Symptomatic/functionally impaired nonfibrotic HP or incomplete response to avoidance
    Acute symptomatic/functional benefit; limited long-term modification (ATS/JRS/ALAT 2020)
  3. 3. mycophenolate OR azathioprine (steroid-sparing)
    MMF 500→1500 mg BID OR AZA 1→2.5 mg/kg/day • PO • BID / daily
    trigger: Progressive inflammatory/chronic HP, steroid-dependent/intolerant
    Steroid-sparing for progressive inflammatory HP; BAL lymphocytosis predicts AZA response (Raimundo 2021 PMID 33621590)
  4. 4. nintedanib (progressive fibrotic HP)
    150 mg BID (100 mg BID Child-Pugh A) • PO • BID with food
    trigger: Progressive fibrotic HP despite avoidance ± immunosuppression
    INBUILD HP subgroup ΔFVC +73.1 mL/yr (Wells 2020 PMID 32145830); overall INBUILD ~107 mL/yr (PMID 31566307)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Subacute/chronic exertional dyspnea + dry cough with a compatible antigen exposure (ATS/JRS/ALAT 2020); Recurrent influenza-like episodes (fever/chills/myalgia/cough) 4–8 h after antigen exposure (Watts/Grammer 2019 PMID 31690386); Inspiratory crackles ± inspiratory squeaks/squawks ± weight loss (ATS/JRS/ALAT 2020).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Hypersensitivity pneumonitis (acute + chronic-fibrotic)** (pulm.hypersensitivity-pneumonitis.v1).
Phenotype framing: §5.5.2 differential-as-data — the ATS/JRS/ALAT 2020 diagnostic-CONFIDENCE-category Bayesian framework encoded as data: confidence is a function of antigen-identification (±IgG), HRCT pattern (typical/compatible/indeterminate), and BAL-lymphocytosis ± histopathology → definite (≥90%) / high (80–89%) / moderate (70–79%) / low (51–69%) / not-excluded. Discriminators carry test characteristics — IPF/UIP (no antigen, no BAL lymphocytosis [~10%], UIP HRCT, older male → pulm.idiopathic_pulmonary_fibrosis.v1); NSIP (younger, GGO-predominant, BAL lymphocytosis overlaps, steroid-responsive); sarcoidosis (perilymphatic nodules + hilar adenopathy, BAL CD4/CD8 >3.5 → pulm.sarcoidosis.v1); CTD-ILD (+ANA/RF/CCP/Scl-70/Jo-1/MDA5/Ro52 + extrathoracic features → rheum MDD, no on-disk dossier); drug-induced ILD (temporal culprit — amiodarone/nitrofurantoin/minocycline/MTX/ICI; reversible if stopped); infection (acute-HP mimic — viral/bacterial/PCP → pulm.cap.core.v1). BAL lymphocyte >20% sens 68.1%/spec 64.8%; >30–40% raises specificity (Adderley 2020 PMID 32265306). Fibrotic-HP UIP-like pattern is the hardest IPF discriminator
Scope: Adult subacute/chronic immune-mediated antigen-driven ILD — establish the NONFIBROTIC-vs-FIBROTIC fork (the dominant prognostic + therapeutic axis) and adjudicate via the ATS/JRS/ALAT 2020 diagnostic-confidence framework at MDD (pulm + thoracic radiology + pathology). Scope excludes IPF/UIP, NSIP, sarcoidosis, CTD-ILD, drug-induced ILD, infection (differential-as-data)

No severity triggers fired against current inputs.

Plan

Regimen axis: **HP antigen-avoidance + anti-inflammatory + steroid-sparing + antifibrotic — ATS/JRS/ALAT 2020**.
1. antigen identification + complete avoidance/remediation identify culprit antigen (structured questionnaire ± serum IgG) then COMPLETE removal/remediation — remove birds/feather/down bedding, mold remediation, stop hot-tub/humidifier, MWF/isocyanate engineering controls or work restriction n/a permanent; verified at every visit (environmental_intervention, first line) — ATS/JRS/ALAT 2020 (PMID 32706311) — antigen identification + avoidance is the CORNERSTONE and the only intervention with a survival signal; unidentified antigen confers worse prognosis. Co-manage with occupational/environmental medicine; re-exposure = treatment failure
2. prednisone 0.5–1 mg/kg/day PO (commonly ~40–60 mg/day) for acute/inflammatory nonfibrotic HP; taper over weeks–months guided by symptoms/PFT/HRCT response (taper documented here — `taper_plan` field does NOT exist in _types.ts) PO once daily then tapered (systemic_corticosteroid, first line) — ATS/JRS/ALAT 2020 — corticosteroid gives acute symptomatic/functional benefit in inflammatory HP but limited long-term disease modification; avoidance remains primary. Taper (not abrupt stop): consolidate 4–8 wk at induction dose then step down over weeks–months with symptom/PFT/HRCT reassessment; monitor glucose/BP/bone/infection during taper
3. methylprednisolone 500–1000 mg IV daily ×3 (pulse) then transition to oral prednisone taper for acute severe HP respiratory failure / AE-like fibrotic deterioration IV pulse ×3 then oral taper (systemic_corticosteroid, rescue) — Acute severe HP / AE-like fibrotic-HP deterioration — high-dose/pulse corticosteroid is common practice with limited controlled evidence; exclude and treat infection/PE/HF first; align ICU/ECMO escalation with transplant candidacy + goals of care (ATS/JRS/ALAT 2020; AE concept from Collard-type ILD-AE definition applied to fibrotic HP)
4. mycophenolate mofetil 500 mg PO BID titrating to 1000–1500 mg BID as tolerated PO BID (antimetabolite_immunosuppressant, second line) — ATS/JRS/ALAT 2020 — steroid-sparing immunosuppression for progressive inflammatory/chronic HP unresponsive to avoidance ± corticosteroid; stabilises lung function in observational cohorts. RxCUI 68149 (mycophenolate mofetil ingredient) NOT independently re-verified via RxNav this pass — see .depth.md §RxCUI-audit (verify-flag). CONTRAINDICATED in pregnancy (teratogen) → use azathioprine branch
5. azathioprine 1 mg/kg/day PO, titrate to ~2–2.5 mg/kg/day (TPMT/NUDT15-informed) PO once daily (antimetabolite_immunosuppressant, second line) — ATS/JRS/ALAT 2020 — alternative steroid-sparing agent; ~61% AZA-responder rate at 12 mo and BAL lymphocytosis predicts favourable response (OR 1.051, 95% CI 1.015–1.089; Raimundo 2021 PMID 33621590). Check TPMT/NUDT15 before start; CBC + LFT surveillance. RxCUI 1256 (azathioprine ingredient) NOT independently re-verified via RxNav this pass — see .depth.md §RxCUI-audit (verify-flag)
6. nintedanib 150 mg PO BID (100 mg BID if hepatic impairment / poor tolerance) PO BID WITH FOOD (antifibrotic_intracellular_TKI, add on) — INBUILD HP subgroup (Wells Lancet Respir Med 2020 PMID 32145830): chronic-HP subgroup nintedanib vs placebo FVC-decline difference +73.1 mL/yr (95% CI -8.6 to 154.8); overall INBUILD progressive-fibrosing ILD annual FVC -80.8 vs -187.8 mL (Δ ~107 mL/yr; Flaherty NEJM 2019 PMID 31566307). RxCUI 1592737 confirmed correct in sibling pulm.idiopathic_pulmonary_fibrosis.v1 §RxCUI-audit 2026-05-16. Diarrhoea most common ADR; hepatotoxicity; bleeding/arterial-thromboembolic caution; CYP3A4/P-gp substrate; AVOID Child-Pugh B/C, reduce to 100 mg BID Child-Pugh A
7. oxygen titrate to resting SpO2 ≥90%; ambulatory O2 for exertional desaturation inhaled continuous if resting SpO2 ≤88% (oxygen, comorbidity specific) — ATS/JRS/ALAT 2020 supportive — LTOT for resting hypoxemia; ambulatory O2 for isolated exertional desaturation in fibrotic HP
8. pulmonary rehabilitation structured exercise + education program n/a program course; maintenance thereafter (rehabilitation, comorbidity specific) — Supportive — improves 6MWD, dyspnea, QoL in fibrotic ILD including fibrotic HP (extrapolated from ILD rehab evidence)
9. lung transplant referral early referral for progressive fibrotic HP without absolute contraindication n/a one-time referral + ongoing co-management (definitive_therapy, comorbidity specific) — Lung transplant is the only disease-modifying option for end-stage progressive fibrotic HP; refer early when progressive despite avoidance + immunosuppression ± antifibrotic (ISHLT candidate-selection principles; ATS/JRS/ALAT 2020)
10. nonfibrotic vs fibrotic phenotype routing (axis selector) nonfibrotic → avoidance + corticosteroid ± steroid-sparing (often reversible); fibrotic → avoidance + (immunosuppression if inflammatory component) + ANTIFIBROTIC if progressive + transplant/palliative n/a at diagnosis + re-evaluated on progression (phenotype_router, comorbidity specific) — Special-pop branch: the ATS/JRS/ALAT 2020 nonfibrotic-vs-fibrotic dichotomy is the dominant therapeutic fork — nonfibrotic is inflammatory/often reversible (anti-inflammatory axis); fibrotic is UIP-like/progressive (antifibrotic axis, prognosis approaching IPF). Fibroblastic-foci profusion HR 2.36 (Chiba 2016 PMID 26836921) + traction-bronchiectasis HR 1.10 (Walsh 2012 PMID 22466512) gate aggressiveness
11. occupational / avoidable-antigen remediation + work restriction environmental remediation + occupational-medicine referral; respirator/engineering controls; job modification or removal if remediation insufficient (farmer's lung, MWF, isocyanate, bird-handler) n/a until verified antigen-free (occupational_intervention, comorbidity specific) — Special-pop branch: occupational/avoidable antigen — the highest-leverage actionable scenario; complete avoidance can arrest or reverse nonfibrotic HP. Verify remediation success at follow-up; partial avoidance often fails
12. unidentified-antigen strategy (empiric remediation + lower IS/antifibrotic threshold) broad empiric environmental remediation (avian/mold/humidifier sweep) + lower threshold for steroid-sparing immunosuppression / antifibrotic + tighter FVC/DLCO surveillance n/a continuous (risk_modified_strategy, comorbidity specific) — Special-pop branch: unidentified antigen confers WORSE survival (ATS/JRS/ALAT 2020) — cannot remove what is not found, so escalate pharmacologic disease modification earlier and surveil more closely
13. azathioprine (pregnancy — preferred steroid-sparing agent; AVOID mycophenolate) 1 mg/kg/day titrating per tolerance (TPMT/NUDT15-informed); minimise corticosteroid; antifibrotic CONTRAINDICATED in pregnancy PO once daily (antimetabolite_immunosuppressant, contraindication substitute) — Special-pop branch: pregnancy — mycophenolate is teratogenic (contraindicated); azathioprine is the preferred steroid-sparing agent if immunosuppression needed; nintedanib contraindicated in pregnancy; minimise corticosteroid dose; co-manage with maternal-fetal medicine. RxCUI 1256 carries the same verify-flag (see .depth.md §RxCUI-audit)
14. nintedanib 100 mg BID (hepatic impairment — Child-Pugh A; AVOID Child-Pugh B/C) / IS renal-hepatic dose-modify 100 mg PO BID (reduced) for Child-Pugh A; AZA/MMF dose-modify and intensify CBC/LFT in hepatic/renal impairment PO BID with food (antifibrotic_intracellular_TKI, contraindication substitute) — Special-pop branch: hepatic/renal impairment — nintedanib reduce to 100 mg BID Child-Pugh A, NOT recommended Child-Pugh B/C (DailyMed label); azathioprine + mycophenolate require dose modification and intensified marrow/hepatic surveillance in hepatic/renal impairment

Setting playbook (outpatient) — Establish HP confidence category + nonfibrotic-vs-fibrotic phenotype at MDD, identify + remove the antigen (cornerstone), initiate anti-inflammatory/steroid-sparing/antifibrotic by phenotype, surveil progression, integrate occupational medicine + transplant + palliative (ATS/JRS/ALAT 2020)
15. antigen identification + complete avoidance/remediation remove/remediate culprit (birds/down, mold, hot tub, MWF, isocyanate) n/a permanent — HP diagnosed (any confidence category) (Cornerstone; only intervention with a survival signal (ATS/JRS/ALAT 2020 PMID 32706311))
16. prednisone (nonfibrotic/inflammatory) 0.5–1 mg/kg/day then taper over weeks–months PO daily then tapered — Symptomatic/functionally impaired nonfibrotic HP or incomplete response to avoidance (Acute symptomatic/functional benefit; limited long-term modification (ATS/JRS/ALAT 2020))
17. mycophenolate OR azathioprine (steroid-sparing) MMF 500→1500 mg BID OR AZA 1→2.5 mg/kg/day PO BID / daily — Progressive inflammatory/chronic HP, steroid-dependent/intolerant (Steroid-sparing for progressive inflammatory HP; BAL lymphocytosis predicts AZA response (Raimundo 2021 PMID 33621590))
18. nintedanib (progressive fibrotic HP) 150 mg BID (100 mg BID Child-Pugh A) PO BID with food — Progressive fibrotic HP despite avoidance ± immunosuppression (INBUILD HP subgroup ΔFVC +73.1 mL/yr (Wells 2020 PMID 32145830); overall INBUILD ~107 mL/yr (PMID 31566307))

Non-pharmacologic actions:
- Occupational/environmental-medicine referral + remediation verification (ATS/JRS/ALAT 2020)
- Early lung transplant referral for progressive fibrotic HP (ISHLT principles)
- Pulmonary rehabilitation + vaccinations
- Smoking cessation
- Palliative care + advance care planning for progressive fibrotic HP (ATS/JRS/ALAT 2020)

AVOID / contraindication checks:
- Antigen avoidance is primary pharmacotherapy is adjunct not substitute (ATS/JRS/ALAT 2020 PMID 32706311)
- Corticosteroid acute benefit limited long term taper not abrupt stop monitor glucose BP bone infection (ATS/JRS/ALAT 2020)
- Azathioprine check TPMT NUDT15 before start then CBC LFT surveillance myelosuppression (azathioprine DailyMed label)
- Mycophenolate TERATOGEN contraindicated in pregnancy REMS counsel contraception (mycophenolate DailyMed label)
- Mycophenolate myelosuppression and infection risk CBC periodic (mycophenolate DailyMed label)
- Nintedanib hepatotoxicity LFT baseline then monthly x3 then periodic (nintedanib DailyMed label)
- Nintedanib bleeding and arterial thromboembolic risk caution on full anticoagulation (nintedanib DailyMed label)
- Nintedanib GI perforation and diarrhoea loperamide then dose reduce 150 to 100 BID (nintedanib DailyMed label)
- Nintedanib not recommended Child Pugh B C reduce to 100 BID Child Pugh A and contraindicated in pregnancy (nintedanib DailyMed label)
- Exclude and treat infection PE HF before attributing acute deterioration to AE like HP (ATS/JRS/ALAT 2020; ILD AE concept)
- Verify antigen remediation success at followup re exposure equals treatment failure (ATS/JRS/ALAT 2020)

Monitoring

Regimen monitoring:
- antigen avoidance verified at every visit re-exposure equals treatment failure (ATS/JRS/ALAT 2020 PMID 32706311)
- FVC q3-6m progression trigger ge 10pct relative decline (ATS/JRS/ALAT 2020; INBUILD PMID 31566307)
- DLCO q6-12m (ATS/JRS/ALAT 2020)
- 6MWT q6m with continuous SpO2 for exertional desaturation (ATS/JRS/ALAT 2020)
- HRCT per change to track nonfibrotic to fibrotic transition (ATS/JRS/ALAT 2020)
- corticosteroid taper glucose BP bone infection surveillance (ATS/JRS/ALAT 2020; corticosteroid DailyMed)
- azathioprine TPMT NUDT15 then CBC LFT periodic (azathioprine DailyMed label)
- mycophenolate CBC LFT periodic and pregnancy avoidance (mycophenolate DailyMed label)
- nintedanib LFT baseline then monthly x3 then periodic GI weight bleeding (nintedanib DailyMed label)
- transplant referral timing for progressive fibrotic HP (ATS/JRS/ALAT 2020; ISHLT principles)

Setting (outpatient) monitoring:
- FVC q3–6 mo, DLCO q6–12 mo, 6MWT q6 mo, HRCT per change (ATS/JRS/ALAT 2020)
- Antigen-avoidance verification at every visit (ATS/JRS/ALAT 2020)
- Immunosuppressant CBC/LFT (TPMT/NUDT15-informed for AZA); nintedanib LFT monthly ×3 then periodic (DailyMed labels)

Follow-up plan: ILD clinic q3–6 mo, occupational/environmental-medicine continuity (verify successful remediation; home/workplace inspection; respirator/work-restriction adherence), transplant clinic co-management for progressive fibrotic HP, comorbidity sweep (Group-3 PH-ILD, lung-cancer surveillance in fibrotic HP, depression, GERD), pulmonary rehab continuity, palliative care + advance care planning for progressive fibrotic HP (ATS/JRS/ALAT 2020)
- Close-out criterion: Follow-up + occupational + transplant + comorbidity + palliative loop booked

Monitoring phase: FVC q3–6 mo + DLCO q6–12 mo (progression = antifibrotic/transplant trigger; ≥10% relative FVC decline = progressive phenotype), 6MWT q6 mo, HRCT per change, ANTIGEN-AVOIDANCE verification at every visit (re-exposure = treatment failure). Immunosuppressant safety: AZA CBC + LFT (TPMT/NUDT15-informed) periodic; MMF CBC + LFT periodic. Antifibrotic safety: nintedanib LFT baseline → monthly ×3 → periodic, GI/weight, bleeding review. Corticosteroid: glucose/BP/bone/infection surveillance during taper (ATS/JRS/ALAT 2020; DailyMed labels)

Disposition

Current setting: outpatient — Establish HP confidence category + nonfibrotic-vs-fibrotic phenotype at MDD, identify + remove the antigen (cornerstone), initiate anti-inflammatory/steroid-sparing/antifibrotic by phenotype, surveil progression, integrate occupational medicine + transplant + palliative (ATS/JRS/ALAT 2020)

Disposition criteria:
- Continue avoidance + phenotype-directed therapy + surveillance if stable (ATS/JRS/ALAT 2020)
- Expedite transplant clinic if progressive fibrotic HP

Escalation triggers (move to higher acuity):
- Acute severe HP / hypoxemic respiratory failure → ED (ATS/JRS/ALAT 2020)
- AE-like deterioration of fibrotic HP (acute dyspnea + new GGO) → ED
- FVC ≥10% relative decline in 6–12 mo despite therapy → escalate to antifibrotic + expedite transplant + palliative

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Acute severe HP with hypoxemic respiratory failure after heavy antigen exposure — high fever + diffuse infiltrate + hypoxemia closely mimicking infection
- [LIFE_THREATENING] Acute-exacerbation-like deterioration of fibrotic HP — acute worsening dyspnea + new bilateral GGO/consolidation on background fibrosis not fully explained by HF/PE/infection (IPF-AE Collard-type definition applied to fibrotic HP)
- [SEVERE] Progressive fibrotic HP — ≥10% relative FVC decline (or worsening fibrosis/symptoms) over 6–12 mo despite antigen avoidance ± immunosuppression

Citations

- ATS/JRS/ALAT 2020 Hypersensitivity Pneumonitis Diagnosis Guideline (Raghu AJRCCM 2020) + INBUILD progressive-fibrosing-ILD program (HP subgroup) [PMID:32706311](https://pubmed.ncbi.nlm.nih.gov/32706311/)
- Cited evidence (PMID 33385222) [PMID:33385222](https://pubmed.ncbi.nlm.nih.gov/33385222/)
- Cited evidence (PMID 35969192) [PMID:35969192](https://pubmed.ncbi.nlm.nih.gov/35969192/)
- Cited evidence (PMID 32145830) [PMID:32145830](https://pubmed.ncbi.nlm.nih.gov/32145830/)
- Cited evidence (PMID 31566307) [PMID:31566307](https://pubmed.ncbi.nlm.nih.gov/31566307/)

Last reconciled with current guidelines: 2026-05-16.
References
  • ATS/JRS/ALAT 2020 Hypersensitivity Pneumonitis Diagnosis Guideline (Raghu AJRCCM 2020) + INBUILD progressive-fibrosing-ILD program (HP subgroup) — PMID:32706311
  • Cited evidence (PMID 33385222) — PMID:33385222
  • Cited evidence (PMID 35969192) — PMID:35969192
  • Cited evidence (PMID 32145830) — PMID:32145830
  • Cited evidence (PMID 31566307) — PMID:31566307