133 INTERSTITIAL LUNG DISEASE (ILD)
Harrison’s Manual of Medicine
INTERSTITIAL LUNG DISEASE (ILD)
Chronic, nonmalignant, noninfectious diseases of the lower respiratory tract characterized by inflammation and derangement of the alveolar walls; >200 separate diseases of known and unknown cause. Each group can be divided into subgroups according to the presence or absence of histologic evidence of granulomas in interstitial or vascular areas (Table 133-1).
Table 133-1 Major Categories of Alveolar and Interstitial Inflammatory Lung Disease
INITIAL EVALUATION History Most pts come to medical attention for dyspnea or persistent cough. Acute presentation (days to weeks) suggests allergy (drugs, fungi, helminths), acute idiopathic interstitial pneumonia, eosinophilic pneumonia, or hypersensitivity. Pts with pulmonary Langerhans cell histiocytosis, desquamative interstitial pneumonitis, Goodpasture’s syndrome, and respiratory bronchiolitis are almost invariably current or former smokers. A careful occupational history is essential. Familial associations have been identified with tuberculous sclerosis and neurofibromatosis, and family clusters are seen with sarcoidosis and familial pulmonary fibrosis.
Physical Examination Usually reveals tachypnea and end-inspiratory crackles.
Chest Imaging X-ray most commonly reveals bibasilar reticular pattern. Honeycombing portends a poor prognosis. High-resolution CT may be sufficiently specific to avoid a need for histologic examination (sarcoidosis, hypersensitivity pneumonitis, lymphangitic carcinoma, asbestosis, pulmonary Langerhans cell histiocytosis).
Tissue and Cellular Examination Rarely, clinical syndrome can be related to a causative agent, but histologic exam is usually necessary. With exception of sarcoidosis, which can often be diagnosed by transbronchial biopsy, most infiltrative diseases require open-lung biopsy for diagnosis. Gallium scans and bronchoalveolar lavage do not yield a specific diagnosis but help to document the extent and character of inflammation.
IDIOPATHIC PULMONARY FIBROSIS History Average age of 50 at presentation; sometimes familial. First manifestations are dyspnea, effort intolerance, and dry cough. Dyspnea and coughing often accompanied by constitutional symptoms (fatigue, anorexia, weight loss). One-third of pts date symptoms to aftermath of viral respiratory infection. Smoking history is common.
Physical Exam Late inspiratory crackles at posterior lung bases. Signs of pulmonary hypertension and clubbing occur late in course.
Laboratory Findings ESR may be elevated. Hypoxemia is common, but polycythemia is rare. Circulating immune-complex titers and serum immunoglobulin levels may be elevated.
Imaging Studies CXR usually reveals patchy, predominantly peripheral reticulonodular markings, prominent in lower lung zones. About 14% of biopsy- proven cases have normal CXR. High-resolution CT may show abnormalities when CXR is normal, such as ground glass opacities with traction bronchiectasis or honeycombing.
PFTs Typically restrictive pattern (Fig. 127-1) with reduced total lung capacity. DLCO often decreased; mild hypoxemia, which worsens with exercise.
Histologic Findings Surgical biopsy usually required. Evidence of usual interstitial pneumonia (UIP) required. Characteristic is heterogeneous appearance of normal lung, interstitial inflammation, fibrosis, and honeycomb change.
Prognosis 5-year survival from diagnosis is 30–50%. No compelling evidence any therapy alters outcome, although glucocorticoids with or without cytotoxic agents (azathioprine, cyclophosphamide) or antifibrotics (colchicine, perfenidone, or interferon g1b) may provide symptomatic benefit.
DESQUAMATIVE INTERSTITIAL PNEUMONIA (DIP) Rare. Found exclusively in smokers in fourth and fifth decades. Better prognosis than idiopathic pulmonary fibrosis (10-year survival ~ 70%).
ILD ASSOCIATED WITH COLLAGEN VASCULAR DISORDERS Usually follows development of collagen-vascular disorder; typically mild but occasionally fatal.
Rheumatoid Arthritis (RA) 50% of pts with RA have abnormal lung function, 25% have abnormal CXR. Rarely causes symptoms. Males more commonly affected than females.
Progressive Systemic Sclerosis Fibrosis with little inflammation; poor prognosis. Must be distinguished from pulmonary vascular disease.
SLE Uncommon complication. When it occurs, it is most often an acute, inflammatory patchy process.
LANGERHANS CELL PULMONARY HISTIOCYTOSIS (EOSINOPHILIC GRANULOMA OR HISTIOCYTOSIS X) Disorder of the dendritic cell system, related to Letterer-Siwe and Hand-Schuller-Christian disease. Develops between 20 and 40 years of age; 90% are present or former smokers. Complicated frequently by pneumothorax. No therapy available.
CHRONIC EOSINOPHILIC PNEUMONIA Affects females predominantly; often a history of chronic asthma. Symptoms include weight loss, fever, chills, fatigue, dyspnea. CXR shows “photonegative pulmonary edema” pattern with central sparing. Very responsive to glucocorticoids.
IDIOPATHIC PULMONARY HEMOSIDEROSIS Characterized by recurrent pulmonary hemorrhage; may be life-threatening. Not associated with renal disease.
GOODPASTURE’S SYNDROME Relapsing pulmonary hemorrhage, anemia, and renal failure. Adult males most commonly affected. Circulating anti-basement membrane antibodies.
INHERITED DISORDERS ILD may be associated with tuberous sclerosis, neurofibromatosis, Gaucher’s disease, Hermansky-Pudlak syndrome, and Niemann-Pick disease.
Most important is removal of causative agent. With exception of pneumoconioses, which are generally not treated except for discontinuation of further exposure and some other specific disorders, therapy is directed toward suppressing the inflammatory process, usually with glucocorticoids. After diagnosis, pts are given oral prednisone, 1 (mg/kg)/d, for 8–12 weeks. Response is assessed by symptoms and PFTs. For idiopathic pulmonary fibrosis and some other disorders, consider immunosuppressive therapy with cyclophosphamide, 1.0 (mg/kg)/d, added to prednisone, 0.25 (mg/kg)/d. Smoking cessation, supplemental oxygen (when PaO2 < 55 mmHg), and therapy for right- sided heart failure and bronchospasm may all improve symptoms.
For a more detailed discussion, see King TE Jr: Interstitial Lung Diseases, Chap. 259, p. 1499, in HPIM-15.