What every physician needs to know:
According to the 2015 National Survey on Drug Use and Health, 27.1 million Americans age twelve years or older use illicit drugs. Pulmonary complications of illicit drug use are common because the lungs are exposed to both the environment and the circulation; hence, all illicit drugs that are inhaled or injected are potentially damaging to the lungs. Physicians should be aware of the pulmonary complications of illicit drug use in order to diagnose these disorders correctly and manage them in a timely fashion.
Non-infectious pulmonary complications
acute non-cardiogenic pulmonary edema
pulmonary arterial hypertension
emphysema and bullous lung disease
Infectious pulmonary complications
pneumonia and bronchitis
septic pulmonary emboli
Are you sure your patient has a pulmonary complication of illicit drug use? What should you expect to find?
Patients with pulmonary complications of illicit drug use are often recognized because of other signs and symptoms of the drug use. However, because patients often abuse illicit drugs surreptitiously, the pulmonary complications are often recognized only with careful questioning of the patient and/or use of laboratory screening for the presence of illicit drugs. Patients who inject heroin or other narcotics or methamphetamines may present with acute pulmonary edema, which may be fatal unless they present to emergency care in a timely fashion, in which case the edema will usually reverse while the patient is receiving supportive care.
Injection drug use with narcotics or with other illicit drugs, particularly crushed oral tablets, may lead to the development of pulmonary granulomatosis. Patients with this condition have progressive shortness of breath with interstitial or emphysematous abnormalities seen on chest imaging. Lung tissue shows the presence of foreign body granulomas that are usually due to talc, in the interstitium and alveolar walls. The rise of illicitly manufactured fentanyl (IMF) has been implicated in the increasing number of opioid-involved overdoses. While primarily injected or snorted, diverted prescription fentanyl patches can also be smoked, with a single case report of pulmonary alveolar proteinosis presumed to result from this route of drug use. IMF is also reported to be mixed with heroin, resulting in a combination with increased potency and rapid progression to overdose and death.
Pulmonary arterial hypertension due to the presence of talc granulomas in the vascular walls is a rare complication of injection drug use. Pulmonary hypertension may also develop in these patients because of co-morbid HIV infection. Severe bullous emphysema is another complication of injection drug use that is related to the presence of talc granulomas. Precocious emphysema, which has been reported in inhaled marijuana as well as in injectors of heroin and methylphenidate, can lead to pneumothorax and pneumomediastinum. Chronic bronchitis and acute bronchospasm are side effects of both injection and inhalation drug use.
Patients who smoke crack cocaine may present with hemoptysis that is due to alveolar hemorrhage. Organizing pneumonia has also been associated with cocaine use.
Extensive studies have been performed in chronic drug abusers to investigate the role of injection and smoked illicit substances on lung function. Chronic marijuana smoking may add to the airway effects of tobacco smoking, while inhaled heroin and inhaled cocaine have been reported to cause acute wheezing and early onset emphysema. Airway hyperreactivity in stimulant use may be related to the additives or solvents with which these drugs are combined, including levamisole, silica and ammonia. Inhalation injury, including thermal damage to the upper airway and trachea, can be caused by “freebasing” cocaine. Exposure to methamphetamine laboratories has caused inhalation injury in illicit drug users and public safety officers. Pleural complications of illicit drug abuse include direct injury to the pleura and resultant pneumothorax from injection and from spontaneous pneumothorax complicating bullous lung disease.
Synthetic cannabinoids are increasing in popularity and have potent agonist activity on cannabinoid receptors as well as dopamine receptors. While their toxicities are primarily neurologic and cardiac in nature, isolated case reports have also noted hemoptysis, pneumothorax and pulmonary infiltrates that resolve with supportive care. These patients may require mechanical ventilatory support depending on the extent of their CNS depression.
Patients who use injected and inhaled drugs are more susceptible to pulmonary infections, including pneumonia and bronchitis, than are those who do not. Aspiration pneumonia is a complication of illicit drug use that results from the altered mental status caused by the drug. Septic pulmonary emboli due to the injection of contaminated illicit drugs via infected needles is another infectious complication of injection illicit drug use. Smoking crack cocaine and other illicit drugs has been implicated in an increased prevalence of pulmonary tuberculosis.
Beware: there are other diseases that can mimic a pulmonary complication of illicit drug use:
Patients with pulmonary complications from abuse of illicit drugs may also be infected with HIV, so the pulmonary complications of HIV infection can overlap with the pulmonary complications of the drug use. The non-infectious and infectious complications of illicit drug use are not unique, as all of these disorders may be seen in patients who do not abuse illicit drugs. Health care providers should be aware of the relationship between illicit drug use and these relatively common pulmonary disorders.
How and/or why did the patient develop a pulmonary complication of illicit drug use?
Injected and inhaled illicit drugs cause direct damage to the pulmonary vasculature, airways and alveoli. Injected drugs can affect the pulmonary vascular permeability and result in pulmonary edema. Sympathomimetic drugs like cocaine and amphetamines can raise the pulmonary arterial pressure. In vivo studies have demonstrated that amphetamine use can lead to DNA damage and pulmonary vascular remodelling. Intravenous injection of foreign material causes septic pulmonary emboli and formation of granulomas along the pulmonary vasculature.
Inhalation drug use results in direct airway inflammation and damage; thermal injury to the upper airway and trachea have also been seen in those who “freebase” cocaine. Injected and inhaled drugs can cause granuloma formation in the alveolar walls, resulting in thinning of those walls, which manifests as emphysema. Inflammation of the interstitium and fibrosis may also be caused by the injection or inhalation of drugs.
Which individuals are at greatest risk of developing a pulmonary complication of illicit drug use?
All individuals who use illicit drugs can develop pulmonary complications. HIV co-infection may be an additive risk factor, particularly for pulmonary vascular and infectious pulmonary complications. Injection drug users who reuse and/or share needles and syringes are at particular risk for infectious complications. Chronic heavy smokers of marijuana may be at risk for obstructive lung disease later in life, while habitual smokers of cocaine can develop chronic airway disease, chronic alveolar hemorrhage, and medial hypertrophy of the pulmonary arteries and resultant pulmonary arterial hypertension.
What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?
There are no routine blood or sputum tests that diagnose the pulmonary complications of illicit drug use. Urine and blood testing to detect illicit drugs may be helpful, particularly in surreptitious users, but many of the parent compounds have short half-lives and readily undergo hydrolysis. In the acute period, metabolites of synthetic cannabinoids are detectable in the serum.
What imaging studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
Routine chest radiography may show findings consistent with the pulmonary complications of drug use, particularly interstitial disease, nodular infiltrates, bullous emphysema, pulmonary infections, pneumothorax, and pneumomediastinum. Chest CT is particularly helpful in diagnosing the more subtle manifestations of these conditions. Nodules of varying sizes, ground-glass opacities, consolidation, air trapping, and emphysema are all detected by CT scanning, particularly using protocols that provide high-resolution, thin-cut images.
What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
Pulmonary function testing is helpful in detecting the type and severity of the pulmonary manifestations of illicit drug use. Abnormalities of airflow detected by spirometry confirm the presence of airways disease, and lung volume and diffusing capacity (DLCO) measurements quantify the degree of interstitial disease and/or emphysema. Increased residual volume, increased functional residual capacity, and reduced DLCO are seen in emphysema, while reduced total lung capacity and reduced DLCO are consistent with interstitial disease.
Echocardiography is used to detect vegetations on cardiac valves that cause septic pulmonary emboli. Echocardiograms are also useful in evaluating cardiac function when patients present with pulmonary edema. Indirect measurement of pulmonary artery pressures are also helpful when illicit drug users are suspected of having pulmonary arterial hypertension; a right heart catheterization can confirm the presence of pulmonary arterial hypertension.
What diagnostic procedures will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy can be useful in the evaluation of interstitial lung disease and pulmonary infections. Surgical lung biopsy is rarely required, as the history of drug use coupled with the radiographic and bronchoscopic findings are generally sufficient to confirm the disease type. Right heart catheterization is necessary to confirm pulmonary arterial hypertension.
What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
Bronchoalveolar lavage and transbronchial or surgical lung biopsy can be useful in detecting infections in carefully selected cases. Transbronchial or surgical lung biopsy can also confirm the presence of talc or other foreign bodies and/or granulomatous inflammation and differentiate between airway and alveolar diseases.
Patients in whom cocaine use is suspected as the causative agent in midline destructive lesions may warrant ANCA testing, as cocaine-induced midline destructive lesions (CIMDL) with associated pulmonary findings can be difficult to distinguish from granulomatosis with polyangiitis (GPA).
If you decide the patient has a pulmonary complication of illicit drug use, how should the patient be managed?
Cessation and abstinence from illicit drug use may result in disease reversal or stabilization, but otherwise, treatment options depend on the specific diagnosis.
Non-infectious complications – Airway diseases may benefit from bronchodilators and inhaled corticosteroid therapy, while select interstitial diseases may benefit from systemic steroids (unless there is fixed fibrosis). Pulmonary vascular disease may benefit from vasodilator therapies, and infectious complications require targeted antibiotic therapy.
Acute pulmonary edema from cocaine or heroin abuse is treated with ventilatory support and general supportive care.
The risks of these management options are generally the same in illicit drug users as in the general population.
What is the prognosis for patients managed in the recommended ways?
The prognoses for the various pulmonary complications are similar compared to patients in the general population. The prognosis is largely affected by whether the patient stops inhalation or ingestion of the illicit drug.
What other considerations exist for patients with a pulmonary complication of illicit drug use?
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- What every physician needs to know:
- Are you sure your patient has a pulmonary complication of illicit drug use? What should you expect to find?
- Beware: there are other diseases that can mimic a pulmonary complication of illicit drug use:
- How and/or why did the patient develop a pulmonary complication of illicit drug use?
- Which individuals are at greatest risk of developing a pulmonary complication of illicit drug use?
- What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?
- What imaging studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
- What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
- What diagnostic procedures will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
- What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of a pulmonary complication of illicit drug use?
- If you decide the patient has a pulmonary complication of illicit drug use, how should the patient be managed?
- What is the prognosis for patients managed in the recommended ways?
- What other considerations exist for patients with a pulmonary complication of illicit drug use?