12-phase flow (12)

1. 1FRAME
   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)
   inputs: hrct, antigen_exposure_questionnaire
   advance: HP confidence category assigned at MDD
2. 2ENTRY
   Suspicion: subacute/chronic exertional dyspnea + dry cough (± recurrent influenza-like episodes 4–8 h post-exposure, inspiratory crackles ± squeaks, weight loss) in a patient with a compatible antigen exposure → exposure history + HRCT (ATS/JRS/ALAT 2020; six-predictor ~95% accuracy Watts/Grammer 2019 PMID 31690386)
   inputs: age
   advance: Engine entered
3. 3CONTEXT
   Structured exposure questionnaire (birds/feathers/down/duvet, mold/damp building, farming/hay/silage, hot tub/humidifier/sauna, metal-working fluid, isocyanates, hobby — pigeon/parrot fancier), temporal symptom-exposure relationship (improvement away from exposure, recurrence on re-exposure), smoking status, full medication review (drug-induced ILD), autoimmune ROS (exclude CTD-ILD), pregnancy status (MMF teratogenicity), baseline SpO2 (ATS/JRS/ALAT 2020)
   inputs: antigen_exposure_questionnaire, occupational_environmental_hobby, smoking_status, current_meds, pregnancy, spo2_room_air, sex
   advance: Exposure + autoimmune + drug + pregnancy context complete
4. 4RED_FLAGS
   Acute severe HP with hypoxemic respiratory failure after heavy antigen exposure (high-fever, diffuse infiltrate, hypoxemia — exclude infection); rapidly progressive fibrotic HP / acute-exacerbation-like deterioration (AE analogue, IPF-AE Collard-type definition applied to fibrotic HP) — exclude infection (viral PCR/bacterial/PCP), PE (CTPA), cardiogenic edema (BNP/echo). Severe resting hypoxemia (LTOT trigger SpO2 ≤88%)
   inputs: spo2_room_air
   actions: workup.ild_acute_exac
   advance: Stabilised or escalated
5. 5INITIAL_WORKUP
   HRCT (typical/compatible/indeterminate pattern + fibrosis grading — mosaic attenuation, air-trapping, three-density/headcheese sign, centrilobular GGO nodules; fibrotic adds reticulation/traction bronchiectasis/honeycombing), serum IgG / specific precipitins to suspected antigens, spirometry + DLCO, 6MWT + continuous SpO2, autoimmune serology (exclude CTD-ILD), CBC, BMP/LFT (pre-immunosuppressant/antifibrotic), TPMT/NUDT15 if AZA contemplated (ATS/JRS/ALAT 2020)
   inputs: hrct, serum_igg_specific_antigen_panel, spirometry_dlco, six_minute_walk_test, ana_rf_ccp_myositis_panel, cbc, bmp_lft
   actions: panel.cbc, panel.lft, panel.renal
   advance: Stage-1 returned
6. 6BRANCHING_WORKUP
   BAL for lymphocyte differential — RECOMMENDED in nonfibrotic HP, SUGGESTED in fibrotic HP (ATS/JRS/ALAT 2020); pooled BAL lymphocyte 42.8% CHP vs 10.0% IPF, >20% sens 68.1%/spec 64.8%, >30–40% higher specificity at the cost of sensitivity (Adderley 2020 PMID 32265306). Transbronchial lung biopsy / transbronchial cryobiopsy / surgical lung biopsy selected by phenotype + residual diagnostic uncertainty per the 2020 algorithm; exposure-elimination or inhalation challenge in selected cases
   inputs: bal_lymphocyte_differential, lung_biopsy
   actions: workup.ild_acute_exac, workup.pulmonary_nodule
   advance: BAL ± biopsy complete; MDD confidence category finalised
7. 7DIFFERENTIAL
   §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
   inputs: hrct, antigen_exposure_questionnaire, serum_igg_specific_antigen_panel, bal_lymphocyte_differential
   advance: HP confidence category assigned at MDD or routed to sibling engine
8. 8RISK_STRATIFICATION
   NONFIBROTIC vs FIBROTIC is the dominant prognostic split (fibrotic HP survival approaches IPF). Poor-prognosis modifiers (each with test characteristics): UIP-like HRCT pattern, extent of fibrosis, traction-bronchiectasis severity (HR 1.10 per unit; Walsh 2012 PMID 22466512), honeycombing (macrocystic HR 1.06 / microcystic HR 1.09; Walsh 2012), fibroblastic-foci profusion (HR 2.36; Chiba 2016 PMID 26836921), UNIDENTIFIED antigen (worse survival — drives empiric remediation + lower immunosuppression/antifibrotic threshold), ↓FVC ↓DLCO, progressive fibrosing phenotype (≥10% relative FVC decline / worsening fibrosis despite avoidance). mMRC dyspnea trend (calc.mmrc) + ROX (calc.rox, AE-like respiratory failure) + A-a gradient (calc.aa_gradient) as registry-resolved adjuncts (HP-specific prognostic index not in registry — see .depth.md schema-gap)
   inputs: spirometry_dlco, six_minute_walk_test, hrct, antigen_exposure_questionnaire
   actions: calc.mmrc, calc.bode
   advance: Nonfibrotic-vs-fibrotic + progression risk + antigen-identification status documented
9. 9TREATMENT
   ANTIGEN AVOIDANCE is the cornerstone (non-pharm; only intervention with a survival signal — complete source removal/remediation; occupational-medicine + possible work restriction). Nonfibrotic/inflammatory: corticosteroid (prednisone — symptomatic/functional benefit acutely, limited long-term efficacy; taper documented in regimen rationale/monitoring — `taper_plan` not in _types.ts); acute severe HP respiratory failure: high-dose/pulse methylprednisolone + supportive. Progressive inflammatory/chronic: steroid-sparing MMF or azathioprine (BAL lymphocytosis predicts AZA response OR 1.051; Raimundo 2021 PMID 33621590). PROGRESSIVE FIBROTIC HP despite avoidance ± immunosuppression: antifibrotic nintedanib (INBUILD HP subgroup ΔFVC +73.1 mL/yr PMID 32145830; overall INBUILD ~107 mL/yr PMID 31566307). Lung transplant referral for progressive fibrotic HP; LTOT/ambulatory O2; pulmonary rehab; vaccinations; palliative integration (ATS/JRS/ALAT 2020; INBUILD)
   inputs: bmp_lft, spo2_room_air, antigen_exposure_questionnaire
   advance: Antigen avoidance + anti-inflammatory/steroid-sparing/antifibrotic + transplant + palliative plan documented
10. 10DISPOSITION
    Admit if acute severe HP / hypoxemic respiratory failure / AE-like fibrotic deterioration (ICU + transplant/ECMO bridge only in candidates — high mortality, align with goals of care); outpatient ILD/pulmonology + occupational-medicine co-management otherwise (ATS/JRS/ALAT 2020)
    advance: Disposition documented
11. 11MONITORING
    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)
    inputs: bmp_lft, spirometry_dlco, antigen_exposure_questionnaire
    advance: Surveillance schedule + progression thresholds + avoidance verification documented
12. 12FOLLOWUP
    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)
    advance: Follow-up + occupational + transplant + comorbidity + palliative loop booked