Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience.

The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnostic approach to such patients. Seventy-two consecutive physician-referred patients had dyspnea greater than one-month duration unexplained by the initial history, physical examination, chest roentgenogram, and spirometry. Patients underwent a standard diagnostic evaluation. A definite cause for dyspnea was recognized in 58 patients, and no answer was found in 14. Twenty-two diseases were recognized in the patient group. Dyspnea was due to pulmonary disease in 26 (36 percent) patients, cardiac disease in ten (14 percent) patients, hyperventilation in 14 (19 percent) patients, and only 3 patients had extrathoracic disease causing dyspnea. Age younger than 40 years, intermittent dyspnea, and normal alveolar-arterial oxygen pressure difference (P[A-a]O2) at rest breathing room air was strongly predictive of bronchial hyperreactivity or hyperventilation. No patient diagnosed as having disease of the lung parenchyma or vasculature had a P(A-a)O2 less than or equal to 20 mm Hg. The differential diagnosis to explain dyspnea in patients with nondirective histories, normal findings from physical examinations, normal chest roentgenograms, and normal spirograms is extensive. The patient's age and measurement of gas exchange at rest help to formulate a diagnostic approach.

Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.

Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspiration pneumonia.

The clinical presentation and course of chemical pneumonitis after inhalation of gastric contents ranges from mild and self-limited to severe and life-threatening, depending on the nature of the aspirate and the underlying condition of the host. In the absence of witnessed inhalation of vomit, diagnosis is difficult and requires a high index of suspicion in a patient who has risk factors for aspiration. In the absence of an obvious predisposition, the abrupt onset of a self-limited illness characterized by dyspnea, cyanosis, and low-grade fever associated with diffuse rales, hypoxemia, and alveolar infiltrates in dependent lobes should suggest aspiration. Treatment consists of supportive care with high-flow oxygen and volume replacement. Bacteria usually play no role in the initial lung injury, and antibiotics should be withheld until there is evidence of superinfection. Prophylactic corticosteroids should not be used. Preventive measures should be employed in patients at high risk for aspiration. Patients with unexplained chronic respiratory syndromes should be evaluated for gastric regurgitation and aspiration.

Interstitial lung disease.

The interstitial lung diseases are comprised of a group of pulmonary disorders characterized clinically by diffuse infiltrates on the chest radiograph and histologically by distortion of the gas exchanging portion of the lung. The physiologic correlates are restriction of lung volumes and impaired oxygenation. The term "interstitial" when applied to these diseases is actually a misnomer because it implies that the inflammatory process is limited specifically to the area between the alveolar epithelial and capillary endothelial basement membranes. The diseases currently grouped as "interstitial" also frequently involve the alveolar epithelium, alveolar space, pulmonary microvasculature, and less commonly, the respiratory bronchioles, larger airways, and even the pleura. The enormous differential diagnosis of interstitial lung disease can be made manageable by understanding that pneumoconiosis, drug-induced disease, and hypersensitivity pneumonitis account for over 80% of the responsible entities and can usually be identified from the patient's history. The nine remaining diseases/disease categories include: sarcoidosis, idiopathic pulmonary fibrosis, bronchiolitis obliterans-organizing pneumonia, histiocytosis X, chronic eosinophilic pneumonia, collagen vascular disease-associated interstitial lung disease, granulomatous vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome, lymphomatoid granulomatosis), Goodpasture's syndrome, and pulmonary alveolar proteinosis. The diagnosis of a specific interstitial lung disease can be made via various means including the patient's history, specific serologies, bronchoalveolar lavage, transbronchial biopsy, and biopsy of extrathoracic tissues or open lung biopsy. A directed diagnostic approach can be formulated based on an understanding of these techniques and a thorough knowledge of the clinical presentations and specific diagnostic criteria for each of the major diseases. This monograph will serve as a guide for the clinician to use in evaluating and treating patients with interstitial lung disease. We begin by reviewing the clinical presentation, diagnostic criteria, and management of specific interstitial lung diseases excluding pulmonary infection, neoplasm, and sarcoidosis. Pneumoconiosis and drug-induced syndromes are not discussed in detail, but the agents responsible and pertinent exposures are presented in tabular form in the discussion of the general diagnostic approach.