The large spectrum of pulmonary complications following illicit drug use: Features and mechanisms q Bruno Mégarbane a,b,⇑ , Lucie Chevillard b a Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, Paris, France b INSERM U1144, Paris-Descartes University, Variability of the response to psychotropic drugs, Paris, France article info Article history: Available online 18 October 2013 Keywords: Drug of abuse Heroin Cocaine Marijuana Pulmonary complication Acute respiratory distress syndrome abstract Damage to lungs may occur from systemic as well as inhalational exposure to various illegal drugs of abuse. Aspiration pneumonia probably represents the most common pulmonary complication in relation to consciousness impairment. Some pulmonary consequences may be specifically related to one given drug. Prolonged smoking of marijuana may result in respiratory symptoms suggestive of obstructive lung disease. Non-cardiogenic pulmonary edema has been attributed to heroin, despite debated mechanisms including attempted inspiration against a closed glottis, hypoxic damage to alveolar integrity, neurogenic vasoactive response to stress, and opiate-induced anaphylactoid reaction. Naloxone-related precipitated withdrawal resulting in massive sympathetic response with heart stunning has been mistakenly impli- cated. In crack users, acute respiratory syndromes called ‘‘crack-lung’’ with fever, hemoptysis, dyspnea, and pulmonary infiltration on chest X-rays have been reported up-to 48 h after free-base cocaine inha- lation, with features of pulmonary edema, interstitial pneumonia, diffuse alveolar hemorrhage, and eosinophil infiltration. The high-temperature of volatilized cocaine and the presence of impurities, as well as cocaine-induced local vasoconstriction have been suggested to explain alveolar damage. Some other drug-related pulmonary insults result from the route of drug self-administration. In intravenous drug users, granulomatous pneumonia with multinodular patterns on thoracic imaging is due to drug contaminants like talcum. Septic embolism from right-sided endocarditis represents an alternative diag- nosis in case of sepsis from pulmonary origin. Following inhalation, pneumothorax, and pneumomedias- tinum have been attributed to increased intrathoracic pressure in relation to vigorous coughing or repeated Valsalva maneuvers, in an attempt to absorb the maximal possible drug amount. In conclusion, pulmonary consequences of illicit drugs are various, resulting in both acute life-threatening conditions and long-term functional respiratory sequelae. A better understanding of their spectrum and the impli- cated mechanisms of injury should help to improve patient management. Ó 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Illicit drug use represents a worldwide health problem, involv- ing about 5% of the world’s adult population and contributing to crime, misery, insecurity and the spread of human immunodefi- ciency virus (HIV) [1]. The two most widely used illicit drugs are cannabis and amphetamine-type stimulants, with a global annual prevalence ranging from 2.6% to 5.0% and 0.3% to 1.2%, respec- tively. Consumption of both cocaine and opiates (including opium and heroin) has remained stable during the last few years, with ranges from 0.3–0.4% to 0.3–0.5%, respectively. However, new chemically engineered psychotropic substances, designed to re- main outside international control recently emerged as recrea- tional drugs. The most commonly identified drug families are piperazine derivatives, synthetic cannabinoids, and cathinones including 4-methylmethcathinone (mephedrone) and methylen- edioxypyrovalerone (MDPV), sold as ‘‘bath salts’’ or ‘‘plant food’’ and used as stimulant substitutes [2]. Each year, between 99,000 and 253,000 deaths are attributed to the use of illicit drugs, accounting for 0.5–1.3% of all-causes of mor- tality in 15–64 year-old adults [1]. Besides the well-known risks of HIV and viral hepatitis transmission in intravenous drug use (IVDU) patients, illicit drugs may acutely or chronically alter organ function, leading to life-threatening conditions or persistent inju- ries. Pulmonary involvement accounts for a major part of illicit drug-related morbidities. Insults to the lung may be attributed either to a direct effect of the drug itself – and thus be mediated by one specific drug-related mechanism of toxicity – or to an indi- rect effect, generally in relation to its route of administration. 0009-2797/$ - see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cbi.2013.10.011 q This work has been presented orally at the 14th Medical Chemical Defense Conference, Munich, 2013. ⇑ Corresponding author at: Department of Medical and Toxicological Critical Care, Lariboisière Hospital, INSERM U1144, Paris-Diderot University, Paris, France. Tel.: +33 1 49 95 84 42. E-mail address: bruno-megarbane@wanadoo.fr (B. Mégarbane). Chemico-Biological Interactions 206 (2013) 444–451 Contents lists available at ScienceDirect Chemico-Biological Interactions journal homepage: www.elsevier.com/locate/chembioint