310.1 🎓 醫孞生版

310.1.0.1 📌 䞀頁重點

310.1.0.1.1 Definition + Scope
310.1.0.1.1.1 ILD
  • Heterogeneous group of > 200 disorders
  • Affects lung parenchyma (interstitium, alveolar walls, small airways, vasculature)
  • Common features:
    • Restrictive physiology (most)
    • Diffuse infiltrates on imaging
    • Variable inflammation + fibrosis
    • Often progressive
310.1.0.1.1.2 Epidemiology
  • Increasing recognition
  • IPF most common idiopathic
  • Sarcoidosis most common granulomatous in young
  • CTD-ILD common in autoimmune patients
310.1.0.1.2 Classification (2013 ATS/ERS Update)
310.1.0.1.2.1 Idiopathic Interstitial Pneumonias (IIPs)
  1. Idiopathic Pulmonary Fibrosis (IPF) — most common, worst prognosis
  2. Idiopathic Non-Specific Interstitial Pneumonia (NSIP)
  3. Cryptogenic Organizing Pneumonia (COP) — formerly BOOP
  4. Acute Interstitial Pneumonia (AIP) — Hamman-Rich
  5. Respiratory Bronchiolitis ILD (RB-ILD) — smoker
  6. Desquamative Interstitial Pneumonia (DIP) — smoker
  7. Lymphoid Interstitial Pneumonia (LIP) — Sjögren, HIV
310.1.0.1.2.2 CTD-Associated ILD
  • Rheumatoid arthritis (RA-ILD)
  • Systemic sclerosis (scleroderma)
  • SLE
  • Sjögren syndrome
  • Polymyositis / dermatomyositis (esp anti-MDA5)
  • Mixed connective tissue disease (MCTD)
  • Antisynthetase syndrome (Jo-1 etc.)
310.1.0.1.2.4 Granulomatous ILD
  • Sarcoidosis
  • Berylliosis
  • Granulomatous fungal / mycobacterial
310.1.0.1.2.5 Other ILDs
  • Lymphangioleiomyomatosis (LAM)
  • Pulmonary Langerhans cell histiocytosis (PLCH)
  • Pulmonary alveolar proteinosis (PAP)
  • Eosinophilic pneumonia (Ch305)
  • Vasculitis (Ch295)
  • Goodpasture syndrome
310.1.0.1.3 Common Idiopathic Interstitial Pneumonias (IIPs)
310.1.0.1.3.1 Idiopathic Pulmonary Fibrosis (IPF)

Demographics: - Older (> 60 yo) - Male predominance - Smoking history common - Median survival untreated: 3-5 years (without therapy)

Pathology: - Usual Interstitial Pneumonia (UIP) pattern - Spatial + temporal heterogeneity - Fibroblast foci - Honeycombing - Acute exacerbations possible

HRCT (UIP Pattern): - Subpleural, basal predominance - Reticular abnormality - Honeycombing (definite UIP) - Traction bronchiectasis - Minimal ground-glass - Absence of features inconsistent with UIP

Diagnosis: - Clinical + HRCT (UIP definite or probable) — biopsy often not needed - Cryobiopsy or surgical biopsy if uncertain - Exclude CTD-ILD, HP, drug, exposure

Treatment: - Antifibrotic (Class I): - Pirfenidone (Esbriet) — anti-TGF-β - Nintedanib (Ofev) — multi-kinase inhibitor (PDGF, FGF, VEGF) - Both slow FVC decline; do not improve symptoms much - Pulmonary rehabilitation - Oxygen therapy - Vaccinations - Lung transplant for select - Treat exacerbations (steroids + supportive)

310.1.0.1.3.2 Non-Specific Interstitial Pneumonia (NSIP)
  • Often associated with CTD (RA, scleroderma, PM/DM)
  • Better prognosis than IPF
  • HRCT: bilateral ground-glass + reticular, basal + peripheral
  • Treatment: immunosuppression (steroids + MMF, azathioprine, rituximab)
310.1.0.1.3.3 Cryptogenic Organizing Pneumonia (COP)
  • Formerly BOOP
  • Subacute, mid-aged patients
  • Migratory consolidation on imaging
  • Dramatic steroid response
  • HRCT: peripheral / subpleural consolidation, often migratory
  • Treatment: oral corticosteroids (prednisone 0.5-1 mg/kg)
  • Most recover; relapses occur
310.1.0.1.3.4 Acute Interstitial Pneumonia (AIP / Hamman-Rich)
  • Rapid onset, ARDS-like
  • High mortality
  • HRCT: bilateral ground-glass + consolidation
  • Pathology: diffuse alveolar damage
  • Treatment: supportive (ventilation), corticosteroids (variable response)
310.1.0.1.3.6 Lymphoid Interstitial Pneumonia (LIP)
  • Sjögren, HIV, immunodeficiency
  • Cysts on HRCT
  • Treatment: immunosuppression; address underlying
310.1.0.1.4 Connective Tissue Disease (CTD) ILD
310.1.0.1.4.1 Common Associations
  • RA-ILD: UIP > NSIP pattern; ↑ mortality
  • Systemic sclerosis: NSIP > UIP; high prevalence (~ 50%)
  • PM/DM: NSIP, OP; anti-MDA5 (rapidly progressive ILD)
  • Antisynthetase syndrome (Jo-1, PL-7, PL-12): NSIP/OP
  • SLE: NSIP, organizing pneumonia, AIP
  • Sjögren: LIP, NSIP
310.1.0.1.4.2 Treatment
  • Immunosuppression (steroids + MMF, AZA, cyclophosphamide, rituximab)
  • Nintedanib for progressive fibrotic phenotype (INBUILD/SENSCIS)
  • Treat underlying CTD
  • Multi-disciplinary (rheumatology + pulmonology)
310.1.0.1.5 Drug-Induced ILD
310.1.0.1.5.1 Common Culprits
  • Amiodarone (lung toxicity 5-10%)
  • Methotrexate
  • Nitrofurantoin
  • Bleomycin
  • Cyclophosphamide
  • Immune checkpoint inhibitors (ICI): pneumonitis in 5-10%
  • TKI inhibitors: gefitinib, erlotinib, others
  • Mammalian target of rapamycin (mTOR) inhibitors
310.1.0.1.5.2 Management
  • Stop offending drug
  • Corticosteroids for severe
  • Specific antidotes rare
310.1.0.1.6 Sarcoidosis
310.1.0.1.6.1 Definition
  • Multisystem granulomatous disorder
  • Non-caseating granulomas
  • Young adults, female slight predominance
  • African American + Scandinavian high rates
310.1.0.1.6.2 Clinical
  • Hilar lymphadenopathy
  • Pulmonary infiltrates (parenchymal involvement late)
  • Skin (erythema nodosum, lupus pernio)
  • Eye (uveitis)
  • Cardiac (Ch295)
  • Neurologic
  • Hepatic, splenic
  • Renal (granulomatous interstitial nephritis, hypercalcemia)
310.1.0.1.6.3 Scadding Stages (CXR)
  • Stage 0: normal
  • Stage I: hilar lymphadenopathy
  • Stage II: lymphadenopathy + parenchymal
  • Stage III: parenchymal alone
  • Stage IV: fibrosis
310.1.0.1.6.4 Diagnosis
  • Tissue (lymph node, lung, skin)
  • Non-caseating granulomas
  • Rule out infection (TB, fungal), other granulomatous
  • ACE level (low specificity)
  • Vitamin D / calcium
  • BAL: CD4/CD8 > 4 (typical, vs HP < 1)
  • Heerfordt syndrome: parotid + uveitis + facial nerve + fever
  • Löfgren syndrome: erythema nodosum + bilateral hilar LAD + arthralgia + fever (good prognosis)
310.1.0.1.6.5 Treatment
  • Observation (many spontaneously remit)
  • Steroids for symptomatic / progressive
  • Methotrexate, azathioprine
  • TNF-α inhibitors (infliximab, adalimumab) — refractory
  • JAK inhibitors emerging
  • Lung transplant for end-stage
310.1.0.1.7 Other Important ILDs
310.1.0.1.7.1 Lymphangioleiomyomatosis (LAM)
  • Sporadic or TSC (tuberous sclerosis) associated
  • Women of childbearing age
  • Cystic lung disease
  • Chylothorax
  • Renal angiomyolipomas
  • Treatment: mTOR inhibitor (sirolimus) — MILES trial
  • Avoid estrogen
  • Lung transplant for end-stage
310.1.0.1.7.2 Pulmonary Langerhans Cell Histiocytosis (PLCH)
  • Smokers (98%)
  • Young adults
  • Upper lobe nodules + cysts (bizarre shapes)
  • BRAF V600E mutation in some
  • Treatment: smoking cessation; steroids; BRAF inhibitors for severe
310.1.0.1.7.3 Pulmonary Alveolar Proteinosis (PAP)
  • Surfactant accumulation in alveoli
  • Autoimmune (anti-GM-CSF antibodies, 90%)
  • Secondary (hematologic, occupational)
  • HRCT: “crazy paving”
  • Treatment: whole lung lavage (mainstay), inhaled GM-CSF (sargramostim), rituximab
310.1.0.1.8 Multidisciplinary Discussion (MDD)
310.1.0.1.8.1 Importance
  • Gold standard ILD diagnosis
  • Combines: clinician + radiologist + pathologist
  • Increases diagnostic accuracy + confidence
  • Reduces unnecessary biopsies
310.1.0.1.8.2 MDD Process
  • Clinical history + physical
  • HRCT pattern
  • Serology + lab
  • BAL (if performed)
  • Biopsy (if performed)
  • Consensus diagnosis
  • Treatment recommendations
310.1.0.1.9 Pulmonary Function Testing in ILD
310.1.0.1.9.1 Common Pattern
  • Restrictive (↓ TLC < 80%)
  • ↓ DLCO
  • Hypoxemia (often exercise-induced first)
310.1.0.1.9.2 Monitoring
  • Serial PFTs (FVC + DLCO + 6MWT)
  • HRCT (less frequent)
  • 6MWT distance
  • Quality of life

310.1.0.2 🩺 床邊速查

  • ILD: 200+ disorders affecting lung parenchyma
  • IPF: UIP pattern, older male, smoker, median survival 3-5 yr untreated
  • NSIP: better prognosis, CTD-associated often
  • COP: migratory consolidation, dramatic steroid response
  • CTD-ILD: RA + scleroderma + PM/DM + Sjögren + MCTD + antisynthetase
  • Sarcoidosis: non-caseating granulomas, BAL CD4/CD8 > 4
  • Antifibrotic (nintedanib, pirfenidone) for IPF + progressive pulmonary fibrosis any cause (INBUILD)
  • MDD is gold standard for ILD diagnosis