Pocket Medicine

PULMONARYQ

INTERSTITIAL LUNG DISEASE

WORKUP OF ILD

Rule out mimickers of ILD

•  Congestive heart failure (✓ BNP, trial of diuresis)

•  Infection: viral, atypical bacterial, fungal, mycobacterial, parasitic

•  Malignancy: lymphangitic carcinomatosis, bronchoalveolar, leukemia, lymphoma

History and physical exam

•  Occupational, travel, exposure (including tobacco), meds, FHx, precipitating event

•  Tempo (acute → infxn, CHF, hypersens pneumonitis, eos PNA, AIP, COP, drug-induced)

•  Extrapulmonary s/s (skin Ds, arthralgias/arthritis, clubbing, neuropathies, etc.)

Diagnostic studies (see Appendix & Radiology inserts)

•  CXR and high-resolution chest CT: reticular, nodular or ground glass pattern upper → coal, silicon, hypersens, sarcoid, TB, RA; lower → IPF, asbestos, scleroderma adenopathy → sarcoidosis, berylliosis, silicosis, malignancy, fungal infections pleural disease → collagen-vascular diseases, asbestosis, infections, XRT

•  PFTs: ↓ DLCO (early sign), restrictive pattern (↓ volumes), ↓ PaO2 (esp. w/ exercise); if also obstructive, consider sarcoid, LAM, silicosis

•  Serologies: ✓ ACE, ANA, RF, ANCA, anti-GBM, HIV

•  Bronchoalveolar lavage: dx infxn, hemorrhage, eosinophilic syndromes, PAP

•  Biopsy (transbronch, CT-guided, VATS, open) if no clear precipitant and w/u unrevealing

ETIOLOGIES OF ILD

Sarcoidosis (NEJM 2007;357:2153; JAMA 2011;305:391)

•  Prevalence: African Americans, northern Europeans and females; onset in 3rd–4th decade

•  Pathophysiology: depression of cellular immune system peripherally, activation centrally

•  Löfgren’s syndrome: erythema nodosum + hilar adenopathy + arthritis (good prognosis)

•  Diagnostic studies: LN bx → noncaseating granulomas + multinucleated giant cells 18FDG PET can be used to identify extent and potentially targets for dx bx ↑ ACE (Se 60%, 90% w/ active dis., Sp 80%, false  in granulomatous diseases)

•  To assess extent: CXR, PFTs, full ophtho exam, ECG, CBC (lymphopenia, ↑ eos), Ca, 24-h urine for Ca, LFTs; ± Holter, echo, cardiac MRI, brain MRI, etc., based on s/s

•  Rx: steroids (eg, prednisone 20–40 mg/d) if sx or extrathoracic organ dysfxn (improves sx, but doesn’t Δ long-term course); hydroxychloroquine for extensive skin disease; anti-TNF, MTX, AZA, mycophenolate or cyclophosphamide for chronic/refractory disease

•  Prognosis: ~2/3 spontaneously remit w/in 10 y (60–80% of stage I, 50–60% stage II, 30% stage III), w/ relapses uncommon; ~1/3 have progressive disease

Iatrogenic

•  Amiodarone (~10%; dose & duration depend.): chronic interstitial pneumonia ↔ ARDS; bx → vacuolized Mf w/ lamellar inclusions on EM; Rx: d/c amio, give steroids

•  Other drugs: nitrofurantoin, sulfonamides, thiazides, INH, hydralazine, gold

•  Chemo: bleomycin (triggered by hyperoxia), busulfan, cyclophosphamide, MTX, etc.

•  XRT: COP/BOOP w/ sharply linear, nonanatomic boundaries; DAH

Idiopathic interstitial pneumonias (IIPs) (AJRCCM 2005;172:268)

•  Definition: ILD of unknown cause; dx by radiographic, histologic and clinical features

UIP, usual interstitial PNA (IP); IPF, idiopathic pulm fibrosis (Lancet 2011;378:1949); NSIP, nonspecific IP; COP, cryptogenic organizing PNA; BOOP, bronchiolitis obliterans w/ organizing PNA; AIP, acute IP (Hamman-Rich syndrome); DIP, desquamative IP; RB-ILD, resp bronchiolitis-assoc ILD.

•  Rx for UIP/IPF: ?? NAC (NEJM 2005;353:2229); pred + AZA harmful (NEJM 2012;366:1968)

Experimental: tyrosine kinase inhib (NEJM 2011;365:1079); pirfenidone (Lancet 2011;377:1760; not avail in U.S.); ? sildenafil (NEJM 2010;363:621); thalidomide for cough (Annals 2012;157:398)

•  Steroids for other IIPs: NSIP (esp. cellular type) and COP (AJRCCM 2000;162:571); ? benefit for AIP and DIP/RB-ILD (for which Pts should stop smoking)

Environmental & occupational exposures (NEJM 2000;342:406; Lancet 2012;379:2008)

•  Pneumoconioses (inorganic dusts)

Coal worker’s: upper lobe coal macules; may progress to massive fibrosis

Silicosis: upper lobe opacities ± eggshell calcification of lymph nodes; ↑ risk of TB

Asbestosis: lower lobe fibrosis, calcified pleural plaques, DOE, dry cough, rales on exam. Asbestos exposure also → pleural plaques, benign pleural effusion, diffuse pleural thickening, rounded atelectasis, mesothelioma, lung Ca (esp. in smokers).

Berylliosis: multisystemic granulomatous disease that mimics sarcoidosis

•  Hypersensitivity pneumonitides (organic dusts): loose, noncaseating granulomas

Antigens: farmer’s lung (spores of thermophilic actinomyces); pigeon fancier’s lung (proteins from feathers and excreta of birds); humidifier lung (thermophilic bacteria)

Collagen vascular diseases (NEJM 2006;355:2655)

•  Rheumatologic disease

Scleroderma: fibrosis in ~67%; PHT seen in ~10% of CREST Pts

PM-DM: ILD & weakness of respiratory muscles; MCTD: PHT & fibrosis

SLE & RA: pleuritis and pleural effusions more often than ILD; SLE can cause DAH

•  Vasculitis (can p/w DAH)

Wegener’s granulomatosis ( c-ANCA) w/ necrotizing granulomas

Churg-Strauss syndrome ( c- or p-ANCA) w/ eosinophilia & necrotizing granulomas

Microscopic polyangiitis ( p-ANCA) w/o granulomas

•  Goodpasture’s syndrome = DAH + RPGN; typically in smokers;  anti-GBM in 90%

•  Lymphangioleiomyomatosis (LAM): cystic, ↑ in , Rx w/ sirolimus (NEJM 2011;364:1595)

Pulmonary infiltrates w/ eosinophilia (PIE) = eos on BAL ± periph. blood

•  Allergic bronchopulmonary aspergillosis (ABPA): allergic reaction to Aspergillus

Criteria: asthma, pulm infiltrates (transient or fixed), skin rxn & serum precipitins to Aspergillus, ↑ IgE to Aspergillus & total (>1000), ↑ eos, central bronchiectasis

Rx: steroids ± itraconazole for refractory cases (NEJM 2000;342:756)

•  Löffler’s syndrome: parasites/drugs → transient pulm infilt + cough, fever, dyspnea, eos

•  Acute eosinophilic PNA (AEP): acute hypox febrile illness; Rx: steroids, tobacco cessation

•  Chronic eosinophilic pneumonia (CEP): “photonegative” of CHF, typically in women

•  Other: Churg-Strauss syndrome; hypereosinophilic syndrome

Miscellaneous

•  Pulm alveolar proteinosis (PAP): accum of surfactant-like phospholipids;  smokers; white & gummy sputum; BAL milky fluid (NEJM 2003;349:2527); Rx w/ lung lavage & GMCSF

•  Langerhans cell granulomatosis (LCG): young  smokers; apical cysts; PTX (25%)

•  Lymphocytic interstitial PNA: polyclonal B-cell infiltration (? lymphoma); Rx: steroids