Pulmonary complications of cocaine use

INTRODUCTION — Cocaine is an alkaloid with anesthetic properties obtained from the leaves of Erythroxylon coca, a shrub native to Central and South America, the West Indies, and Indonesia. Coca's unique chemical properties have led to its use in social, religious, and medicinal settings for centuries.

Cocaine was first isolated from coca leaves in 1859. Over the following sixty years, many over-the-counter products containing cocaine were marketed, including asthma remedies and "French Wine Cola," the predecessor of Coca-Cola. While a "pinch of coca leaves" was included in John Styth Pemberton's original 1886 recipe for Coca-Cola, the company began using decocainized leaves in 1906 when the Pure Food and Drug Act was passed. The first cocaine-related fatalities were reported in 1893, and in 1914 the Harrison Narcotic Act banned the nonprescription use of cocaine-containing products [1].

Cocaine is a widely abused substance around the world. Its use has been increasing, often in combination with heroin, fentanyl, or xylazine [2-4]. Toxicity in a variety of organs has been reported, including the cardiovascular, respiratory, and central nervous systems [5]. The pulmonary sequelae that result from cocaine use will be reviewed here. Other aspects of cocaine use are discussed separately. (See "Cocaine: Acute intoxication" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse" and "Cocaine use disorder: Epidemiology, clinical features, and diagnosis".)

PHARMACOLOGY — The local anesthetic properties of cocaine derive from its ability to stabilize cell membranes and block neuronal sodium channels. It also has potent sympathomimetic and central nervous system stimulant effects due to interference with the reuptake of catecholamines and serotonin. (See "Cocaine: Acute intoxication".)

Cocaine hydrochloride is a heat-labile fine white powder that can be inhaled nasally ("snorted") or injected intravenously but cannot be smoked. However, when boiled with baking soda and water and the resultant precipitate filtered or extracted with ether or alcohol, cocaine yields a lipid-soluble, heat-stable, free-base form that can be smoked ("free basing"). This form is commonly called "rock" (because of its gross appearance) or "crack" (because of the characteristic crackling sound it makes when heated and smoked) [6].

Crack cocaine may be smoked by itself through a pipe, or it may be mixed with cannabis or tobacco in cigarettes. It is rapidly absorbed through the pulmonary circulation and reaches the central nervous system within seconds. Its half-life in the blood is 60 to 90 minutes [7].

PATHOLOGY AND PATHOPHYSIOLOGY — An autopsy series that examined lung histopathology among 52 cocaine users found that the findings were similar regardless of the route of cocaine use [8]. Histopathologic changes included lung congestion (88 percent), intraalveolar edema (77 percent), acute hemorrhage (58 percent), chronic hemorrhage (40 percent), and interstitial pneumonitis (38 percent). A high resolution chest computed tomography (HRCT) study of the lungs of patients with a history of cocaine use demonstrated a number of architectural changes, including ground-glass opacities, consolidations, paraseptal emphysema, and centrilobular nodules [9].

Mechanisms of cocaine-induced pulmonary injury include thermal airway injury, direct cellular toxicity, provocation of inflammatory damage (eg, eosinophilia, diffuse alveolar damage), barotrauma, and vasospasm leading to ischemia. Profound pulmonary arterial vasospasm can cause ventilation-perfusion lung scan abnormalities consistent with pulmonary embolism [10,11].

Because many cocaine abusers also smoke cannabis or tobacco, it is difficult to determine whether some physiologic alterations (eg, decreased diffusing capacity) or pathologic changes (eg, chronic inflammation) are specifically caused by cocaine [12-14]. A review of electronic health records of 8244 cocaine users found a correlation between cocaine use and asthma, COPD, and pneumonia, independent of tobacco use. While this study was not designed to assess causality, it does suggest that there may be pulmonary changes specific to cocaine [15].

Although smoking crack cocaine accounts for most cases of pulmonary toxicity, intravenous use, snorting, and "body packing" (the practice among smugglers of swallowing packets of cocaine to facilitate transport) have also resulted in lung damage. (See "Internal concealment of drugs of abuse (body packing)".)

Acute pulmonary toxicity and crack lung — "Crack lung" refers to a syndrome of diffuse alveolar damage and hemorrhagic alveolitis that occurs within 48 hours of smoking crack cocaine. This presentation is associated with diffuse alveolar hemorrhage or occasionally bronchoalveolar lavage eosinophilia on bronchoscopy, and diffuse alveolar damage and hyaline membrane formation in biopsy or autopsy specimens [16-19]. The roles of particulates, nitric oxide generation, and bronchial artery constriction in the acute lung injury are not known [20].

The pathophysiology of acute cocaine intoxication is discussed separately. (See "Cocaine: Acute intoxication", section on 'Pathophysiology'.)

Acute eosinophilic pneumonia — Acute eosinophilic pneumonia is occasionally reported within hours to days of crack or intranasal cocaine use [6,17,21,22]. When severe, it can have a similar presentation to “crack lung.” In a case report, onset of an eosinophilic pleural effusion and pulmonary eosinophilia developed a few days after the second use of crack cocaine [23]. The mechanism by which cocaine induces pulmonary eosinophilia is not known, although cigarette smoking also appears to be a risk factor for acute eosinophilic pneumonia. (See "Overview of pulmonary eosinophilia" and "Pleural fluid eosinophilia" and "Idiopathic acute eosinophilic pneumonia", section on 'Etiology'.)

Pneumothorax and pneumomediastinum — Spontaneous pneumothorax and pneumomediastinum have been reported among cocaine users, both those who smoke cocaine and those who use it intranasally [24-30]. A common practice among crack smokers is to perform a Valsalva maneuver after inhalation. Smoking partners also exhale forcefully into each other's mouths to increase uptake of the drug. These practices may lead to barotrauma followed by the development of pneumothorax, pneumomediastinum, subcutaneous emphysema, or pneumopericardium [24-30]. Underlying foreign body granulomatous inflammation and fibrotic and/or emphysematous pulmonary parenchymal changes may be predisposing factors [31,32].

Chronic toxicity — Long-term cocaine use is associated with a variety of histopathologic changes in the lung, including foreign body granulomatosis, bronchiectasis, and recurrent alveolar hemorrhage with hemosiderosis [13,16,19,21,33-43]. Recurrent alveolar hemorrhage from prolonged crack cocaine use has been associated with development of severe pulmonary fibrosis [44]. It is speculated that these pathologic manifestations of chronic cocaine use result from direct cellular toxicity, thermal airway injury, and/or an inflammatory or hypersensitivity response. (See "Inhalation injury from heat, smoke, or chemical irritants" and "Inhalation injury from heat, smoke, or chemical irritants", section on 'General care'.)

Foreign body granulomatosis is caused by inhaled or intravenous exposure to excipients such as talc (silica), cellulose, mannitol, and cotton fibers [37,45]. The consequences of foreign body granulomatosis include hilar adenopathy, chronic interstitial lung disease, tissue infarction due to pulmonary vascular impingement by embolized material or perivascular granulomas, and bullous emphysema. Systemic toxicity, such as vasculopathy and agranulocytosis, has also been reported in cases where cocaine has been adulterated with the antihelminthic agent levamisole [46]. The pathophysiology of foreign body granulomatosis is discussed separately. (See "Foreign body granulomatosis", section on 'Pathophysiology'.)

A few cases of organizing pneumonia (previously known as bronchiolitis obliterans organizing pneumonia) have been described among cocaine users, but the mechanism by which cocaine might incite this type of inflammation is not known [47]. (See "Overview of bronchiolar disorders in adults", section on 'Proliferative bronchiolitis' and "Cryptogenic organizing pneumonia", section on 'Histopathologic diagnosis of organizing pneumonia'.)

Pulmonary vascular disease — Cocaine use may cause pulmonary vascular disease through foreign body granulomatosis, vasoconstrictive effects, and thromboembolic disease. (See "The epidemiology and pathogenesis of pulmonary arterial hypertension (Group 1)".)

Pulmonary hypertension is thought to be one of the consequences of foreign body granulomatosis, due to vascular occlusion from embolized adulterant material (eg, talc, silica, cellulose, mannitol) or vascular impingement by perivascular granulomata. (See "Foreign body granulomatosis", section on 'Pathophysiology'.)

It is thought that chronic cocaine use can also lead to pulmonary hypertension through vasoconstriction of the pulmonary vasculature [48]. However, the evidence for this is limited and conflicting [49-53]. In a small number of cases, pulmonary arterial hypertension has developed in cocaine users without other clear cause [49,54]. Echocardiographic measurement of systolic pulmonary artery pressure was performed in a group of 88 cocaine users, most of whom smoked cocaine, and compared with matched controls [54]. Cocaine use was associated with a significantly higher pulmonary artery pressure and a fivefold increase in the odds of having pulmonary hypertension.

In one autopsy study of 20 cocaine users, four patients had pulmonary artery medial hypertrophy of small or medium sized arteries in the absence of foreign particle microembolization or evidence of thromboembolic disease; three used by intravenous injection and one by oral inhalation [51]. In contrast, a separate autopsy series of 28 cocaine users found no pathologic findings suggestive of pulmonary arterial hypertension, although three had evidence of pulmonary thromboembolism and one of pulmonary infarction [52].

CLINICAL FEATURES — A significant portion of individuals who smoke crack develop nonspecific respiratory complaints. A survey of public health center walk-in patients who admitted to having smoked crack in the previous 30 days revealed that 95 percent had at least one respiratory symptom in the previous week [55]. In addition, cocaine use can lead to both acute and more slowly developing serious respiratory symptoms, depending on the route of use and the presence of underlying respiratory disease [21,34,56,57].

Smoking crack cocaine can result in the acute onset of shortness of breath and cough within 48 hours of crack inhalation; some patients also have fever, chest or back pain, sputum production, or hemoptysis [13,16,17,21,40,58]. Shortness of breath may progress rapidly to respiratory failure in patients with acute pulmonary toxicity or acute eosinophilic pneumonia.

Among patients with asthma, snorting or smoking cocaine can cause acute and potentially life-threatening asthma exacerbations with dyspnea, wheezing, chest tightness, and cough [40,56,57,59]. Patients with a history of asthma or chronic obstructive pulmonary disease who smoke cocaine on an ongoing basis also have a higher readmission rate than those who only smoke tobacco [60].

Chronic cocaine-induced pulmonary injury can cause slowly progressive dyspnea, chronic productive or nonproductive cough, and intermittent hemoptysis [21,34,56,57]. In some patients, cough is productive of black sputum (melanoptysis). Melanoptysis is probably due to the inhalation of carbonaceous residue from materials used to ignite crack, such as matches or rags soaked with butane or alcohol. It may also relate to the practice of scraping off and resmoking the black tarry residue left in the pipe after initial use [61].

The presence of thermal burns on fingers or thumbs, the result of handling crack pipes, may raise a suspicion for cocaine as an etiology for pulmonary pathology in patients denying cocaine use [62].

A discussion of the nonpulmonary manifestations of cocaine intoxication is provided separately. (See "Cocaine: Acute intoxication", section on 'Clinical manifestations'.)

EVALUATION AND DIAGNOSIS — The initial evaluation and diagnosis of the various cocaine-induced lung diseases typically includes laboratory studies, pulmonary function testing, pulse oximetry, and chest imaging. Bronchoscopy and bronchoalveolar lavage are frequently performed when diffuse radiographic opacities are noted. Lung biopsy is occasionally required when the radiographic pattern is atypical or the patient fails to improve with supportive care.

Laboratory — There are no specific laboratory findings for acute or chronic cocaine-induced pulmonary toxicity. Routine laboratory testing may include complete blood count with differential, blood chemistries, and blood and sputum cultures, as indicated. The main role of these tests is to exclude alternative diagnoses accounting for the patients’ signs and symptoms. The evaluation of patients with acute cocaine intoxication is discussed separately. (See "Cocaine: Acute intoxication", section on 'Laboratory and radiographic evaluation'.)

Plasma D-dimer testing is commonly used as an initial test in patients suspected of having acute pulmonary embolism. Its accuracy in differentiating acute pulmonary embolism (PE) from vasoconstriction due to cocaine has not been reported, although cocaine use is associated with false positive D-dimer testing. In a prospective, observational study of 4,356 patients undergoing D-dimer measurement for possible PE, multivariate analysis identified cocaine use as a risk factor for a false positive D-dimer [63]. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

The role for toxicology testing for cocaine and its metabolites is limited. Cocaine is rapidly metabolized and detectable in blood and urine only briefly (ie, a few hours) after use, so a negative test does not exclude the possibility that cocaine use caused the pulmonary findings. Benzoylecgonine is the major urinary metabolite of cocaine and can be detected in the blood for two days after cocaine use and in the urine for several more days. (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis", section on 'Drug testing'.)

As cocaine use is a risk factor for HIV infection with its associated complications, HIV testing is appropriate in cocaine-using patients with respiratory complaints. (See "Screening and diagnostic testing for HIV infection".)

Pulmonary function testing — Pulmonary function testing is generally obtained as part of an evaluation of dyspnea in patients with a subacute or chronic presentation. Studies examining the effect of crack cocaine use on pulmonary function have yielded variable results [64]. In the largest study of 202 habitual users of crack cocaine, a mild, but statistically significant reduction in diffusing capacity was noted, but spirometry and lung volumes were normal [64]. The cause of the mild reduction in diffusing capacity is not known, but may be related to the accumulation of hemosiderin-laden macrophages in the alveoli. (See 'Bronchoalveolar lavage' below.)

Pulse oximetry is monitored to determine the adequacy of supplemental oxygen administration. Arterial blood gases (ABGs) are obtained to evaluate for alveolar hypoventilation (if mental status is depressed) and to assess the severity of the gas transfer abnormality. ABGs obtained in patients with acute lung injury due to cocaine usually show acute respiratory alkalosis, hypoxemia, and an elevated alveolar-arterial oxygen gradient (calculator 1).

Imaging — A chest radiograph is obtained in most patients presenting with respiratory complaints in the setting of cocaine use. Abnormalities on chest radiograph among patients presenting with chest pain or dyspnea after using cocaine include atelectasis, pneumothorax, hemopneumothorax, pneumopericardium, pneumomediastinum (image 1 and image 2), focal consolidation, and diffuse parenchymal ground glass (image 3) or consolidative opacities [65].

High resolution computed tomography (HRCT) of the chest is usually obtained for further evaluation of an abnormal chest radiograph. Typical findings include interlobular septal thickening, peribronchial nodules, ground glass opacities, and areas of consolidation that may evolve into cavitations (image 4) [40,47,65]. Patients who inject cocaine intravenously may develop foreign body granulomatosis, due to talc and other agents mixed with the cocaine. The radiographic findings of foreign body granulomatosis include small 2 to 3 mm well-defined nodules, confluent perihilar masses, and ground glass opacities; these findings are discussed separately. (See "Foreign body granulomatosis", section on 'Imaging'.)

Computed tomography with pulmonary angiography (CTPA) is obtained when the acute onset of dyspnea or chest pain suggests possible pulmonary embolism. Visualization of an intraluminal filling defect by CTPA is helpful in differentiating vasoconstriction of the pulmonary arterial circulation due to cocaine from pulmonary embolism. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

Bronchoalveolar lavage — When patients present with respiratory symptoms and radiographic opacities after using cocaine, the main purpose of bronchoscopy with bronchoalveolar lavage (BAL) is to evaluate for infection, eosinophilia, and alveolar hemorrhage. Most patients with respiratory failure will undergo bronchoscopy with BAL, often immediately after intubation. To identify diffuse alveolar hemorrhage (DAH), BAL is performed with three sequential wedged lavages from the same segment. The presence of increasingly bloody lavage returns is diagnostic of DAH. Samples are also sent for total and differential cell counts and microbiologic analysis (including tests for opportunistic infections), and cytology. (See "Basic principles and technique of bronchoalveolar lavage" and "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease".)

Bronchoalveolar lavage findings in patients with crack lung include carbonaceous debris, eosinophils, Charcot-Leyden crystals, hemosiderin-laden macrophages, and increased cell counts [23,34,37]. Asymptomatic habitual cocaine users have an increased percentage of hemosiderin-laden macrophages compared with tobacco smokers or nonsmokers, suggestive of recurrent subclinical alveolar hemorrhage [37]. Extreme eosinophilia (>25 percent) is indicative of eosinophilic pneumonia.

Lung biopsy — For patients with progressive symptoms and diffuse interstitial disease (without significant emphysematous changes) on chest CT scan, and an unclear diagnosis, transbronchial biopsy is often performed at the time of flexible bronchoscopy (in the absence of contraindications). (See "Role of lung biopsy in the diagnosis of interstitial lung disease", section on 'Transbronchial lung biopsy' and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures", section on 'Transbronchial biopsy'.)

Video-assisted thoracoscopic or open lung biopsy is performed when the diagnosis remains unclear after the above evaluation and the patient's lung function is deteriorating or severely impaired. Generally, an echocardiogram is performed prior to either of these procedures to exclude the possibility that pulmonary hypertension is the cause of dyspnea or hypoxemia. (See "Role of lung biopsy in the diagnosis of interstitial lung disease".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of the acute onset of cocaine-induced pulmonary symptoms includes acute pulmonary toxicity from crack cocaine, acute eosinophilic pneumonia, acute respiratory distress syndrome (from infection, aspiration, and other causes), pulmonary embolism, heart failure, pneumonia, coronavirus disease 2019 (COVID-19) [66], and acute coronary syndrome. The differential diagnosis of chronic cocaine-induced lung toxicity and foreign body granulomatosis includes interstitial lung disease (eg, organizing pneumonia, idiopathic interstitial pneumonias, lymphangitic carcinomatosis, pneumoconioses), and granulomatous lung disease (eg, sarcoidosis, berylliosis, miliary tuberculosis), and emphysema due to cigarette smoking. These possibilities are differentiated by the results of laboratory testing, imaging studies, cultures, bronchoalveolar lavage, and occasionally lung biopsy. (See "Evaluation of diffuse lung disease by conventional chest radiography", section on 'Basic patterns' and "Approach to the adult with interstitial lung disease: Diagnostic testing", section on 'Causes of ILD'.)

High-resolution computed tomography (HRCT) of the chest helps to characterize the pattern of involvement. Focal consolidation is more consistent with pneumonia, pulmonary infarct, or organizing pneumonia, while diffuse ground glass or consolidative opacities are consistent with "crack lung" or acute respiratory distress syndrome due to other causes. Computed tomography with pulmonary angiogram (CTPA) can help differentiate thromboemboli from acute pulmonary vasoconstriction. (See 'Imaging' above and "High resolution computed tomography of the lungs" and "The diffuse alveolar hemorrhage syndromes" and "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults".)

Pulmonary hemorrhage and/or eosinophilic pneumonia due to cocaine are identified by sequential bronchoalveolar lavage (BAL) with cell counts and cultures. (See 'Bronchoalveolar lavage' above and "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease", section on 'Hemorrhagic BAL' and "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease", section on 'Eosinophilic BAL'.)

When an acute coronary syndrome due to the vasoconstrictive effects of cocaine is in the differential due to a combination of chest pain and dyspnea, an electrocardiogram and measurement of serum troponin I are helpful for identifying myocardial ischemia. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse", section on 'Diagnostic evaluation'.)

In habitual cocaine users with chronic respiratory symptoms, pulmonary radiographic opacities, and no history of other exposures (eg, beryllium, silica) or clear evidence of infection, lung biopsy may be necessary to determine whether the patient has occult infection, organizing pneumonia, foreign body granulomatosis, or other non-cocaine-related interstitial lung disease. Usually, video-assisted lung biopsy is performed to obtain a sample of sufficient size, although transbronchial biopsy may be performed first when foreign body granulomatosis is suspected. (See "Role of lung biopsy in the diagnosis of interstitial lung disease" and "Foreign body granulomatosis", section on 'Lung biopsy' and "Foreign body granulomatosis", section on 'Histopathology' and "Cryptogenic organizing pneumonia", section on 'Diagnosis'.)

For patients with insidious onset of dyspnea, desaturation on exertional pulse oximetry, a reduced diffusing capacity, and no evidence of radiographic parenchymal opacities, an echocardiogram is used to screen for pulmonary hypertension as an explanation of the patient's symptoms; right heart catheterization would be needed for confirmation. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)

COMORBIDITIES

Pulmonary infection — Cocaine users, particularly crack smokers, are at increased risk for pulmonary infections. To some degree, this is a consequence of cocaine's depressant effects on lymphocyte and macrophage activity and mucociliary clearance [67,68]. However, much of the excess risk probably relates to the association of crack use with other behavioral patterns that predispose to pulmonary infection. These include:

●Concomitant use of narcotics or alcohol, which increase the risk of aspiration. (See "Overview of pulmonary disease in people who inject drugs".)

●Increased exposure to tuberculosis because of the crowded conditions, transient population, and frequent coughing from crack use that are found in crack houses [69]. In addition, it has been suggested that crack use may directly predispose to infection with tuberculosis by suppressing antimicrobial activity of alveolar macrophages [69].

●Increased frequency of malnutrition.

●Increased risk of HIV infection because of concomitant intravenous drug use or the practice of exchanging sex for drugs. (See "Screening and diagnostic testing for HIV infection".)

Respiratory tract cancers — The carcinogenicity of cocaine smoking has been much less well studied than that of tobacco smoking. Several reports have shown that smoking cannabis and cocaine can cause similar histologic and molecular changes in the bronchial epithelium as those found in tobacco smokers [70]. A case-control study, which included approximately 1200 patients with lung cancer or upper aerodigestive cancer and 1000 control subjects, investigated the link between heavy crack cocaine smoking and cancer. After adjusting for potential confounders, including ever-use of tobacco or alcohol, use of crack cocaine was associated with an increased risk of developing upper aerodigestive cancers [71]. Lung cancers were more common among crack cocaine smokers, but the increase was not statistically significant after accounting for demographic factors, use of tobacco, and alcohol use.

MANAGEMENT — Treatment of the pulmonary consequences of cocaine use is largely based on observations from case reports. Supportive care is the most important modality, along with cessation of crack cocaine use. Referral to a drug use disorder treatment program is advised for all patients. This is particularly important in cases where lung injury has occurred secondary to chronic cocaine use. (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis" and "Stimulant use disorder: Treatment overview".)

The general management of acute cocaine intoxication is discussed separately. (See "Cocaine: Acute intoxication".)

Crack lung — The initial management of crack lung is supportive to maintain adequate oxygenation while the acute lung injury resolves. Noncardiogenic pulmonary edema is treated with administration of supplemental oxygen and conservative fluid management to reduce edema fluid formation. Many patients require ventilatory support, either noninvasive positive pressure ventilation or endotracheal intubation with mechanical ventilation for respiratory failure [18]. For patients with acute intoxication who require intubation, use of a nondepolarizing neuromuscular blocker, such as rocuronium, is preferred over succinylcholine. (See "Noncardiogenic pulmonary edema" and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "Cocaine: Acute intoxication", section on 'Initial management'.)

As the differential diagnosis of "crack lung" includes infections, such as community acquired pneumonia, aspiration pneumonia, and opportunistic infections (in patients with underlying AIDS), broad-spectrum antibiotics are usually initiated on presentation while awaiting culture results [34,72,73]. (See "Treatment of community-acquired pneumonia in adults who require hospitalization" and "Treatment of community-acquired pneumonia in adults in the outpatient setting".)

There are no definitive data supporting the use of glucocorticoids for alveolar hemorrhage caused by cocaine, but case reports have described clinical and radiographic improvement with administration of methylprednisolone or prednisone [19,65]. It is possible that some of these patients had a component of acute eosinophilic pneumonia, which is described after smoking crack cocaine and improves with systemic glucocorticoids (see 'Acute eosinophilic pneumonia' above). The limited role of glucocorticoids for relatively early, moderate to severe acute respiratory distress syndrome (ARDS) is discussed separately. (See 'Acute eosinophilic pneumonia' above and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults", section on 'Glucocorticoids'.)

In the presence of significant eosinophilia in the BAL fluid (ie, >25 percent), treatment would follow that for acute eosinophilic pneumonia. (See 'Acute eosinophilic pneumonia' below.)

Acute eosinophilic pneumonia — The diagnosis of acute eosinophilic pneumonia (AEP) due to cocaine is based on the presence of eosinophilia in the BAL fluid (ie, >25 percent). The management of AEP in cocaine users includes complete cessation of cocaine use and supportive care with supplemental oxygen and ventilatory support, as needed. In addition, after exclusion of infection, systemic glucocorticoid therapy is usually initiated following the management of idiopathic AEP, which is discussed separately. (See "Idiopathic acute eosinophilic pneumonia", section on 'Treatment'.)

Initial therapy is based on the severity of disease:

●In the absence of respiratory failure, initial treatment is with oral prednisone (40 to 60 mg daily)

●In the presence of respiratory failure, methylprednisolone (60 to 125 mg every six hours) is given intravenously until respiratory failure resolves and is then changed to oral therapy with prednisone

Pneumothorax, hemothorax, and pneumomediastinum — The management of pneumothorax, hemothorax, and pneumomediastinum depends upon the severity of respiratory impairment and the size of the pneumothorax or hemothorax. All patients are provided with supportive care, including supplemental oxygen. The indications for tube thoracostomy and other treatment options for pneumothorax are discussed separately. Generally, pneumomediastinum does not require specific therapy in adults. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children" and "Treatment of secondary spontaneous pneumothorax in adults".)

Organizing pneumonia — When organizing pneumonia develops in association with crack cocaine use, systemic glucocorticoids are the mainstay of treatment, as in the treatment of cryptogenic organizing pneumonia. (See "Cryptogenic organizing pneumonia", section on 'Treatment'.)

Foreign body granulomatosis — The management of foreign body granulomatosis is largely supportive with cessation of drug use, administration of supplemental oxygen, and ventilatory support, as needed. (See "Foreign body granulomatosis", section on 'Management'.)

Bronchoconstriction — Based on clinical experience, bronchodilators, such as inhaled beta agonists, are used to treat cocaine-induced bronchoconstriction and wheezing. The general treatment of asthma exacerbations is discussed separately. (See "Acute exacerbations of asthma in adults: Home and office management".)

Pulmonary hypertension — The role of vasodilator therapy in pulmonary hypertension due to foreign body granulomatosis has not been well-studied. If vasodilator testing is undertaken in this setting, it is most safely done with short acting agents and concomitant monitoring of pulmonary artery pressures and cardiac output in an experienced center. The general management of pulmonary arterial hypertension is discussed separately. (See "Foreign body granulomatosis", section on 'Pulmonary hypertension' and "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cocaine use and cocaine use disorder".)

SUMMARY AND RECOMMENDATIONS

●Pharmacology – Cocaine hydrochloride is a heat-labile fine white powder that can be inhaled nasally ("snorted") or injected intravenously but cannot be smoked. However, when cocaine is boiled with baking soda and water, and the resultant precipitate filtered or extracted with ether or alcohol, the product known as "crack cocaine" can be smoked ("free-basing"). (See 'Pharmacology' above.)

●Types of lung injury – Acute cocaine pulmonary toxicity occurs within 48 hours of smoking cocaine; patients typically develop a combination of fever, dyspnea, hypoxemia, and diffuse ground glass or consolidative opacities. This presentation has been termed "crack lung." (See 'Acute pulmonary toxicity and crack lung' above.)

Other acute pulmonary complications of cocaine use include acute eosinophilic pneumonia, pneumothorax, and pneumomediastinum. (See 'Acute eosinophilic pneumonia' above and 'Pneumothorax and pneumomediastinum' above.)

Long-term cocaine exposure can result in recurrent alveolar hemorrhage, hemosiderosis, bronchiectasis, foreign body granulomatosis, hilar lymphadenopathy (due to foreign body granulomatosis), organizing pneumonia, pulmonary infarction, and bullous emphysema. Pulmonary hypertension and thromboembolic disease are additional potential causes of hypoxemia in chronic cocaine users. (See 'Chronic toxicity' above and 'Pulmonary vascular disease' above.)

●Clinical features – Symptoms and signs of both acute and chronic cocaine-induced pulmonary injury may include fever, chest or back pain (frequently pleuritic), dyspnea, cough with or without sputum production, hyperpnea, wheezing (potentially life-threatening exacerbations in patients with a history of asthma), hemoptysis, melanoptysis (expectoration of black sputum), and finger burns. (See 'Clinical features' above.)

●Diagnostic evaluation – The diagnosis of the various cocaine-induced lung diseases is based upon a history of cocaine use and compatible clinical, radiographic, and bronchoscopic findings. Most patients with acute respiratory failure and radiographic opacities suggestive of "crack lung" will undergo bronchoscopy and sequential bronchoalveolar lavage (BAL). BAL samples are sent for cell counts, differential, microbiologic analysis, and cytology. (See 'Evaluation and diagnosis' above and 'Differential diagnosis' above.)

In patients with persistent respiratory symptoms, pulmonary radiographic opacities, and no clear evidence of infection or pulmonary eosinophilia, lung biopsy is sometimes performed to determine whether the patient has occult infection, organizing pneumonia, foreign body granulomatosis, or other non-cocaine-related interstitial lung disease. (See 'Differential diagnosis' above.)

●Treatment of “crack lung” – Treatment of "crack lung" is largely supportive, following the usual measures for acute lung injury, with administration of supplemental oxygen, bronchodilator therapy (when wheezing is present), and noninvasive or invasive mechanical ventilation when indicated. Broad spectrum antibiotics are usually administered pending the results of microbiologic investigations. (See 'Crack lung' above and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults".)

The role of glucocorticoids is limited and aligns with the guidance for acute respiratory distress syndrome (ARDS), which reserves glucocorticoids for patients with a concomitant glucocorticoid-responsive illness or relatively early, moderate to severe ARDS, as described separately. (See 'Crack lung' above and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults", section on 'Glucocorticoids'.)

The presence of significant eosinophilia in the BAL fluid (>25 percent) indicates a diagnosis of acute eosinophilic pneumonia, which is associated with crack cocaine use. The treatment regimen should include systemic glucocorticoids as described for idiopathic acute eosinophilic pneumonia. (See 'Acute eosinophilic pneumonia' above and "Idiopathic acute eosinophilic pneumonia", section on 'Treatment'.)

●Other management considerations – Discussions of the management of pneumothorax, acute eosinophilic pneumonia, organizing pneumonia, foreign body granulomatosis, exacerbations of asthma, and pulmonary hypertension are provided separately. (See "Idiopathic acute eosinophilic pneumonia", section on 'Treatment' and "Foreign body granulomatosis", section on 'Management' and "Acute exacerbations of asthma in adults: Home and office management" and "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy" and "Thoracostomy tubes and catheters: Indications and tube selection in adults and children" and "Cryptogenic organizing pneumonia", section on 'Treatment'.)

●Prevention of chronic pulmonary toxicity – Prevention of chronic pulmonary toxicity requires cessation of crack cocaine use; referral to a substance use disorder treatment program is advised for all patients. (See 'Management' above and "Stimulant use disorder: Treatment overview".)