311.1 🎓 醫孞生版

311.1.0.1 📌 䞀頁重點

311.1.0.1.1 Idiopathic Pulmonary Fibrosis (IPF) — Deep Dive
311.1.0.1.1.1 Definition
  • Specific form of chronic, progressive, fibrosing IIP
  • Unknown cause
  • Histopathologic / radiologic UIP pattern
  • Older adults (> 60 yo)
  • Median survival 3-5 years untreated (worse than many cancers)
311.1.0.1.1.2 Epidemiology
  • Incidence: 5-15 per 100,000
  • Increasing recognition
  • Male > female (1.5-2x)
  • Risk factors:
    • Smoking (strong association)
    • GERD (microaspiration hypothesis)
    • Occupational exposures (dust, metal)
    • Familial (15-20% have family history)
    • Genetic: MUC5B promoter polymorphism, TERT/TERC (telomere), SFTPC, surfactant protein mutations
311.1.0.1.1.3 Pathogenesis
  • Repetitive alveolar epithelial injury
  • Aberrant wound healing
  • Fibroblast / myofibroblast proliferation
  • Excessive collagen + ECM deposition
  • “Two-hit” hypothesis: genetic predisposition + environmental insult
311.1.0.1.1.4 Clinical Features
  • Progressive exertional dyspnea
  • Dry cough (often debilitating)
  • Bibasilar inspiratory crackles (“velcro crackles”)
  • Clubbing (50%)
  • No constitutional symptoms (usually)
  • Late: cor pulmonale, pulmonary HTN, hypoxemia
311.1.0.1.1.5 Diagnosis (2018 ATS/ERS/JRS/ALAT)

Required: - Exclusion of other known ILD causes (HP, CTD, drug, exposure, environmental) - HRCT pattern: definite, probable UIP OR indeterminate / alternative - Multidisciplinary discussion (MDD) - Biopsy if uncertain (cryobiopsy or surgical)

HRCT Patterns:

Definite UIP: - Subpleural + basal predominance - Reticular pattern - Honeycombing + traction bronchiectasis - Absence of features inconsistent

Probable UIP: - Subpleural + basal predominance - Reticular + traction bronchiectasis - No honeycombing - Absence of features inconsistent

Indeterminate: - Variable distribution, subtle features - May need biopsy

Alternative Diagnosis: - Features pointing to other cause (cysts, GG, nodules, consolidation, mosaic, upper/mid lung)

311.1.0.1.1.6 Pulmonary Function
  • Restrictive: ↓ TLC, ↓ FVC, normal or ↓ FEV1, FEV1/FVC ≥ 0.7
  • ↓ DLCO (often most sensitive)
  • Hypoxemia (especially exercise-induced)
311.1.0.1.1.7 Treatment

Antifibrotic (Class I): - Pirfenidone (Esbriet) - 801 mg TID with meals - Side effects: photosensitivity, GI, LFT elevation - CAPACITY (2011), ASCEND (2014) trials - Nintedanib (Ofev) - 150 mg BID - Side effects: diarrhea, LFT, weight loss - INPULSIS (2014), INBUILD (2019) trials - Both slow FVC decline by ~ 50% - No improvement in symptoms or survival benefit demonstrated in trials, but slows progression - May reduce acute exacerbations

Supportive Care: - Smoking cessation - Treat GERD (PPI, fundoplication if severe) - Oxygen for hypoxemia - Pulmonary rehabilitation - Vaccinations (flu, pneumococcal, COVID, RSV) - Palliative care for advanced

Lung Transplant: - Only “cure” - Refer early when FVC < 70-80% or DLCO < 50% (some advocate at diagnosis) - 5-year survival post-transplant ~ 50% - Bilateral preferred

311.1.0.1.1.8 Acute Exacerbation of IPF
  • Sudden worsening (within 30 days)
  • Often preceded by infection, surgery, biopsy
  • New ground-glass on HRCT
  • Diagnosis of exclusion (infection, HF, PE)
  • 30-day mortality 50%+; 6-month mortality 70%+
  • Treatment: supportive, often high-dose steroids (debated efficacy)
  • Antifibrotic may not prevent
311.1.0.1.1.9 Prognosis
  • GAP score (Gender, Age, Physiology)
  • 3-year mortality 25-50%
  • Acute exacerbation: very high mortality
  • Lung transplant: improves survival
311.1.0.1.2 Non-Specific Interstitial Pneumonia (NSIP)
311.1.0.1.2.1 Categorization
  • Cellular NSIP: inflammatory predominant
  • Fibrotic NSIP: fibrotic predominant
311.1.0.1.2.2 Demographics
  • Mid-aged (40-50 yo)
  • Female predominance
  • Strong CTD association (40-60%): RA, scleroderma, PM/DM
311.1.0.1.2.3 Clinical
  • Dyspnea + cough
  • Slower progression than IPF
  • Often non-smokers
311.1.0.1.2.4 HRCT
  • Bilateral ground-glass opacity
  • Reticular pattern
  • Basal + peripheral predominance
  • No or minimal honeycombing
  • Sub-pleural sparing (sometimes)
311.1.0.1.2.5 Treatment
  • Immunosuppression: corticosteroids + MMF / AZA / rituximab
  • Cyclophosphamide for severe / progressive
  • Treat underlying CTD if applicable
311.1.0.1.2.6 Prognosis
  • Better than IPF
  • 5-year survival 80% (cellular) vs 60% (fibrotic)
311.1.0.1.3 Cryptogenic Organizing Pneumonia (COP)
311.1.0.1.3.1 Background
  • Formerly BOOP (bronchiolitis obliterans organizing pneumonia)
  • Subacute (weeks-months)
  • Mid-aged adults
311.1.0.1.3.2 Etiology Categories
  • Cryptogenic (idiopathic)
  • Secondary to: infection, drugs, autoimmune (RA), radiation, transplant rejection
311.1.0.1.3.3 Clinical
  • Subacute dyspnea + cough
  • Fever, malaise
  • Weight loss
  • Flu-like prodrome
311.1.0.1.3.4 HRCT
  • Peripheral / subpleural consolidation
  • Migratory (moves over weeks)
  • Ground-glass opacity
  • Bronchocentric pattern
  • Reverse halo sign (“atoll sign”)
311.1.0.1.3.5 Pathology
  • Organizing pneumonia: granulation tissue plugs in alveoli + bronchioles
  • Masson bodies
311.1.0.1.3.6 Treatment
  • Oral corticosteroids dramatic response
  • Prednisone 0.5-1 mg/kg/d for 4-12 weeks → slow taper over 6-12 months
  • Most recover
  • Relapses common (30-50%) — slow taper important
311.1.0.1.3.7 Prognosis
  • Generally good
  • Recovery most cases
311.1.0.1.4 Acute Interstitial Pneumonia (AIP / Hamman-Rich Syndrome)
311.1.0.1.4.1 Definition
  • Idiopathic ARDS-like syndrome
  • Rapid onset (days-weeks)
  • Diffuse alveolar damage (DAD)
311.1.0.1.4.2 Clinical
  • Acute respiratory failure
  • Sometimes febrile
  • Healthy individuals
  • ICU management often required
311.1.0.1.4.3 Treatment
  • Mechanical ventilation
  • High-dose corticosteroids
  • ECMO for severe
311.1.0.1.4.4 Prognosis
  • High mortality (50-70%)
  • Survivors may have residual fibrosis
311.1.0.1.6 Pulmonary Langerhans Cell Histiocytosis (PLCH)
311.1.0.1.6.1 Demographics
  • Almost exclusively smokers (98%)
  • Young adults (20-40 yo)
  • Female:male equal
311.1.0.1.6.2 Pathology
  • Langerhans cell infiltration with bronchiolocentric distribution
  • BRAF V600E mutation in some
  • Stellate granulomas → cysts
311.1.0.1.6.3 HRCT
  • Upper + mid lung predominance
  • Bizarre-shaped cysts + nodules
  • Often with pneumothorax
  • Spares costophrenic angles
311.1.0.1.6.4 Clinical
  • Cough, dyspnea
  • Pneumothorax (recurrent)
  • Constitutional symptoms (some)
  • Diabetes insipidus (rare; pituitary involvement)
311.1.0.1.6.5 Treatment
  • Smoking cessation (mainstay)
  • Steroids (severe)
  • Cladribine (refractory)
  • BRAF inhibitors (vemurafenib, dabrafenib) for BRAF-mutated severe
  • Lung transplant for end-stage
311.1.0.1.7 Lymphangioleiomyomatosis (LAM)
311.1.0.1.7.1 Background
  • Almost exclusively in women of childbearing age
  • Sporadic OR TSC-associated (tuberous sclerosis complex)
  • Spectrum: lung, kidney (AML), lymphatic
311.1.0.1.7.2 Pathology
  • Smooth muscle proliferation (LAM cells) along airways + lymphatics + blood vessels
  • Cysts replace lung tissue
311.1.0.1.7.3 Clinical
  • Progressive dyspnea
  • Pneumothorax (recurrent)
  • Chylothorax (chylous effusion)
  • Hemoptysis
  • TSC features (skin, neuro, renal)
311.1.0.1.7.4 HRCT
  • Diffuse thin-walled cysts (uniform distribution)
  • Throughout lung
  • Renal angiomyolipoma (CT/MRI abdomen)
311.1.0.1.7.5 Diagnosis
  • HRCT + TSC features OR chylothorax / AML
  • Genetic testing for TSC1/TSC2
  • VEGF-D serum elevation
  • Lung biopsy if uncertain
311.1.0.1.7.6 Treatment
  • Sirolimus (mTOR inhibitor) — Class I (MILES trial 2011)
  • Stabilizes FEV1 decline
  • Continued use needed
  • Avoid estrogen (worsens disease)
  • Avoid pregnancy (worsens disease)
  • Pleurodesis for recurrent pneumothorax
  • Lung transplant for end-stage
  • TSC management (epilepsy, renal)
311.1.0.1.8 Pulmonary Alveolar Proteinosis (PAP)
311.1.0.1.8.1 Categorization
  • Autoimmune (90%): anti-GM-CSF antibodies; adult onset
  • Secondary (10%): hematologic malignancy, infections, immune deficiency, dust exposure
  • Congenital: rare; mutations in surfactant proteins or GM-CSF receptor
311.1.0.1.8.2 Pathology
  • Surfactant accumulation in alveoli
  • Surfactant lipoproteinaceous material
  • PAS-positive
311.1.0.1.8.3 HRCT
  • “Crazy paving” (ground-glass + septal thickening)
  • Bilateral, often symmetric
311.1.0.1.8.4 Diagnosis
  • BAL: milky fluid + PAS+ material
  • Anti-GM-CSF antibody (autoimmune)
  • Specific clinical context
311.1.0.1.8.5 Treatment
  • Whole lung lavage (mainstay): bronchoscopic + general anesthesia
  • Inhaled GM-CSF (sargramostim, molgramostim): for autoimmune
  • Rituximab: for refractory autoimmune
  • Plasmapheresis: refractory cases
311.1.0.1.8.6 Prognosis
  • Variable; many improve with treatment
  • Some progression to fibrosis
311.1.0.1.9 Sarcoidosis (Pulmonary)
311.1.0.1.9.1 See Ch295 for systemic + cardiac involvement
311.1.0.1.9.2 Pulmonary Sarcoidosis

Demographics: - Young adults (20-40) - African American (4x), Scandinavian high rates - Female slight predominance

Clinical: - Dyspnea, cough - Constitutional (fever, weight loss, fatigue) - Often asymptomatic (incidental CXR) - Löfgren syndrome (good prognosis): erythema nodosum + hilar LAD + arthralgia + fever - Heerfordt syndrome: parotid + uveitis + facial nerve + fever

Imaging — Scadding Stages: - Stage 0: normal CXR - Stage I: hilar/mediastinal LAD alone - Stage II: LAD + parenchymal - Stage III: parenchymal alone - Stage IV: fibrosis

Diagnosis: - Tissue biopsy (lymph node, lung, skin) - Non-caseating granulomas - Exclude infection (TB, fungal) - BAL: CD4/CD8 > 4 (typical) - ACE elevated (low sensitivity) - Vitamin D / calcium (hypercalcemia from granuloma 1α-hydroxylase) - 18-F FDG-PET: active inflammation

Treatment: - Observation: many spontaneously remit (~ 50%) - Glucocorticoids: for symptomatic / progressive (prednisone 20-40 mg/d → taper) - Methotrexate, azathioprine, leflunomide: steroid-sparing - TNF-α inhibitors (infliximab, adalimumab): refractory - JAK inhibitors (tofacitinib, ruxolitinib): emerging - Lung transplant: end-stage stage IV

Prognosis: - Stage I: 70-80% spontaneous remission - Stage II: 50% - Stage III-IV: less likely to remit; chronic - Mortality 5%; depends on extent

311.1.0.1.10 Approach to Diagnosing ILD
311.1.0.1.10.1 Algorithm
  1. Detailed history: occupational, environmental, drug, family, autoimmune, smoking
  2. Physical exam: skin, joints, lymph nodes, neurologic
  3. Labs: CBC, ANA, RF, anti-CCP, ANCA, autoantibodies, immunoglobulins, ACE, IgE, Aspergillus IgE, hepatitis B/C, HIV
  4. HRCT: assess pattern (UIP, NSIP, OP, mosaic, cysts, nodular, etc.)
  5. PFTs + DLCO + 6MWT
  6. BAL (selected cases)
  7. Cryobiopsy or surgical biopsy (if MDD uncertain)
  8. MDD: consensus diagnosis
311.1.0.1.10.2 When to Biopsy
  • HRCT inconclusive
  • Atypical features
  • Uncertain about IPF vs CTD vs HP
  • Treatment decision depends on diagnosis

311.1.0.2 🩺 床邊速查

  • IPF: UIP pattern, older male, median survival 3-5 yr untreated; antifibrotic (nintedanib, pirfenidone) standard
  • INBUILD 2019: nintedanib for PPF any cause, not just IPF
  • NSIP: better prognosis, CTD-associated, immunosuppressive
  • COP: migratory consolidation, dramatic steroid response, relapses common
  • AIP: ARDS-like, high mortality
  • PLCH: smokers + bizarre cysts + upper lobe + smoking cessation
  • LAM: women + cysts + TSC + sirolimus
  • PAP: anti-GM-CSF + crazy paving + whole lung lavage
  • Sarcoidosis: non-caseating granulomas, BAL CD4/CD8 > 4, Scadding stages