Diagnosis 4: Pleural blebs, bullous and centriacinar emphysema, lymphocytic bronchiolitis, and black pigment


Conclusion: A small, post-operative air leak resolved over the next 3 weeks. The right chest tube was removed, and he was discharged about 3 months after his first pneumothorax. He has remained clinically stable since discharge and continues his directly observed therapy for tuberculosis.

Comment: This patient had a series of life-threatening events at the onset of AIDS. Extrathoracic tuberculosis was treated promptly, but during his convalescence, he developed bilateral pneumothoraces probably related to his apical bullous disease noted on his first chest x-ray. Concomitantly, he developed an infarct and bilateral lung opacities diagnosed on open lung biopsy as acute interstitial pneumonia with granulomas.

This patient's medical problems may all have been related to smoking crack cocaine. Even the tuberculosis may be linked to cocaine smoking. In an epidemiologic study from California, 16% of patients with newly-diagnosed tuberculosis smoked crack cocaine, and 1/3 of these persons frequented crack houses where cocaine is sold and used [1]. In this HIV-positive man with increased susceptibility to tuberculosis, use of crack cocaine in a poorly-ventilated crack house room with another infected person could have caused disease. Other crack cocaine-associated conditions that our patient had include pneumothorax, pulmonary infarction, and interstitial pneumonia. Each of these conditions is discussed below.


Respiratory Complications of Smoking Crack Cocaine

Introduction: In the U.S., habitual cocaine users may number between 5 and 8 million persons [2,3]. Several recent reviews describe the pulmonary complications, which are mostly acute, in crack cocaine smokers [2-5]. In a group of 202 crack smokers, mostly recruited from substance-abuse treatment programs, acute respiratory symptoms occurring 1-12 hr after smoking cocaine included cough productive of black sputum (44%), chest pain (38%), hemoptysis (6%), and cardiac palpitations (53%). In this group, studies confirmed the lack of abnormalities in pulmonary function except for a mild decrease in diffusing capacity [6]. Other complications have been described in small numbers of smokers.

Barotrauma Following Smoking Crack Cocaine

Clinical features: At least 12 cases of barotrauma associated with smoking crack cocaine have been reported in detail (Table 1). Patients were young adults; ages ranged from 19-26, and men outnumbered women (9:3). Patients presented within hours of smoking with pleuritic chest pain, neck pain, dyspnea, sore throat, or muffled voice. Hamman's sign (precordial systolic crunch) was heard in 6. At least three had a previous history of smoking cigarettes ± marijuana. Radiographs showed pneumomediastinum (PM) and interstitial emphysema in most and an accompanying pneumothorax (PT) in 3. Spontaneous resolution occurred over a few days in all but one, who required a tube thoracostomy. In another series of 71 patients, who presented with chest pain or dyspnea following crack smoking and were studied radiographically, 2 had PM; one, PT; and one, hemopneumothorax [7].

Radiologic features: Mediastinal air shifts the mediastinal pleura away from the heart border. The "continuous diaphragm sign" results from air outlining the entire diaphragm. Lateral films, which may be needed for diagnosis in 50% of cases, show retrosternal air [8]. Subcutaneous emphysema and PT may also be present [9].

Mechanism: PM may be primary and caused by extreme exertion (athletes), asthma, parturition, straining at stool, sneezing, coughing, or emesis. Secondary pneumomediastinum may develop following positive-pressure ventilation, chest trauma, or rupture of the esophagus (Boerhaave syndrome) [9]. During cocaine smoking, barotrauma results from vigorous breathing, deep inhalation followed by a Valsalva maneuver, or from mouth-mouth positive pressure from an accomplice. Alveolar air under increased pressure ruptures into the connective tissue or lymphatics of the interlobular septa or bronchovascular bundle and dissects to the mediastinum ± soft tissue planes in the neck. Rupture of air from the mediastinum or dissection peripherally to the pleura with rupture of a pleural bleb causes pneumothorax. The cause of acute chest pain ± dyspnea in 62 crack smokers without radiographic changes described by Eurman, et al. is not clear. They postulate that pulmonary interstitial emphysema without PM or PT may be a factor [7].

Parenchymal Abnormalities Following Smoking Crack Cocaine: Vascular Abnormalities

Parenchymal abnormalities can be classified as vascular or inflammatory. Vascular abnormalities include noncardiogenic pulmonary edema, pulmonary hemorrhage, and pulmonary infarction. Mechanisms are not understood, but vasoconstriction, mediated directly or via the central nervous system and well-documented in the systemic circulation, may occur in the pulmonary arteries. The only evidence for this possibility is the finding of thickened walls of medium- and small-sized pulmonary arteries in autopsies of 4 of 20 selected persons who died from acute cocaine intoxication [16]. However, no quantitation was done to substantiate the claim that these four individuals differed from the others or the 10 control subjects. Increased numbers of hemosiderin-laden macrophages were found in the lungs of 7 of the 20 autopsies, but in none of the controls [16]. If acute constriction of the pulmonary arteries occurs when cocaine is smoked, capillary leakage could account for the transient edema [7,17,18], frequent hemoptysis (sometimes massive) [6,19-22], and rare infarction [23] that have been reported.

Alternatively, direct damage to the capillary bed may occur. Evidence for such damage is the mild impairment in diffusing capacity, but not other parameters of pulmonary function, in smokers of crack cocaine [6]. This finding is supported by the increased clearance of inhaled 99mTc diethylenetriamine pentaacetate (DTPA) found in crack smokers compared to non-smokers. This defect reflects damage to the alveolar-capillary membrane and is similar to that found in smokers of tobacco cigarettes. Clearance was more rapid in the upper than lower lobes of crack smokers and was not dependent on time elapsed since last smoking crack [24]. This abnormality might contribute to edema and hemorrhage.

Acute Parenchymal Injury Following Smoking Crack Cocaine

The second type of abnormality consists of parenchymal inflammation. An acute eosinophilic pneumonia, rapidly reversible with steroids, was described in several instances. These cases are sometimes accompanied by a peripheral eosinophilia. Bronchiolitis obliterans organizing pneumonia was described in one case [25].

Clinical features: The 6 reported patients (Table 2) ranged in age from 16 to 47; men and women were equally represented. Symptoms began suddenly within hours of smoking or more gradually after a week of intermittent use. Hemoptysis occurred in 3. All smoked tobacco cigarettes, and 2 smoked marijuana, but all denied current intravenous drug use. Presenting symptoms included cough, dyspnea, chest pain, wheeze, and nausea. On admission, fever was noted in 5. Rales or wheezes were noted on physical examination. Blood eosinophilia (>5%) occurred in 3. Chest radiographs showed bilateral, patchy or diffuse, alveolar opacities except in one case where bilateral small nodules occurred [25]. Most patients required oxygen therapy, and 4 required ventilatory assistance. Most received antibiotics for possible pneumonia. Treatment with steroids in 5 was accompanied by rapid improvement. One patient improved spontaneously.

Histologic features: The histologic appearance is based on 2 open biopsies, 3 transbronchial biopsies, and 1 bronchial wash (Table 3). Various terms have been used to describe the histologic changes. All of the patterns represent acute lung injury, and most fit into the pattern of acute eosinophilic pneumonia (organizing diffuse alveolar damage with eosinophils) (Table 4). Acute eosinophilic pneumonia involves the interstitium and alveoli. Hyaline membranes may be present. Organization occurs in the interstitium and air spaces including airways, and a COP-like picture can be seen. The hallmark is the abundance of eosinophils among the lymphocytes, plasma cells, and scattered PMNs in the interstitium and mixed with alveolar macrophages in air spaces. Type II cell hyperplasia may be prominent. Granulomas have not been described [28] although they can be found in about 10% of cases of chronic eosinophilic pneumonia [29]. The diagnosis of acute eosinophilic pneumonia can be made by finding BAL fluid eosinophilia, as in case 6.

Other findings in the biopsies included hemorrhage and black pigment [5,30,31]. Other reports indicate that adulteration of crack with silica, silicates, or cellulose can lead to granulomatous inflammation or interstitial fibrosis in sniffers or smokers [32-34].


Table 4. Summary of Histologic Features of Eosinophilic Pneumonia [28]

*Described in chronic eosinophilic pneumonia of >2 weeks' duration [29]


Radiographic changes: These consist of diffuse, bilateral, alveolar, interstitial, or mixed opacities.

Treatment: Some patients have spontaneous resolution. Treatment with steroids can be begun when other possible diagnoses, especially infections, have been excluded. Response to steroids is rapid and without relapse. Recurrence, however, may follow resumption of smoking crack [19]. Patients with acute eosinophilic pneumonia following crack smoking appear to respond in the same manner as those with the idiopathic form of the disease [28].

Summary of findings in our case: Our patient is unusual in having bilateral, large pneumothoraces that did not respond to chest tube suction and that required talc pleurodesis and wedge resection. Also, he is older than other reported patients. On his first admission, he already had apical bullae, which may have predisposed to PT. The diagnosis of PT related to crack smoking was not considered until the wedge resection (4th biopsy) when the large number of black, pigment-laden macrophages (iron stain negative) in alveolar spaces, as well as in the interstitium, were first noted. (A history of crack smoking was then obtained.) Intrapleural blebs, as well as subpleural bullae, were noted in the resected lung tissue, but an eosinophilic pleuritis, often found in lung tissue resected for pneumothorax, was absent.

The coagulation necrosis seen in the transbronchial biopsy of our patient probably signified pulmonary infarction related to smoking crack. Infarction would have been impossible to diagnose clinically in our patient with concomitant pneumothorax and interstitial pneumonia, but the biopsy makes the diagnosis likely.

The organizing interstitial pneumonia without significant eosinophils and with granulomas may be a new type of pneumonia in patients who smoke crack cocaine, may represent a reaction to an adulterant of crack, or may represent an eosinophilic pneumonia in a patient who had recently received corticosteroids (last dose 7 days previously). The histologic pattern (organizing, interstitial pneumonia with granulomas) closely resembles an eosinophilic pneumonia that lacks eosinophils, and granulomas have been described in eosinophilic pneumonia of greater than 2 weeks' duration [29]. In retrospect, black pigment-laden macrophages were present in that biopsy also. We favor a diagnosis of crack-associated interstitial pneumonia. It is very unlikely that the granulomas represented a residue of his tuberculosis. They appeared to be integrated into the inflammation and of the same age. Cultures of the biopsy were negative for the tubercle bacillus, and sputum cultures were repeatedly negative after the first hospitalization. The rapid response to steroids further excludes an infectious etiology.

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Clinical Summary

Comments: mw6825@itsa.ucsf.edu

Table of Contents

Last revised 5/12/97

Copyright 1997 Martha L. Warnock. All rights reserved.