Airway effects of marijuana, cocaine, and other inhaled illicit agents

Several substances besides tobacco are inhaled for recreational purposes, including marijuana, crack cocaine, amyl and butyl nitrites, heroin, methamphetamine, and phencyclidine. Abuse of most of these inhaled substances has risen in recent years, thereby increasing concern about potential pulmonary and other medical complications. Regular marijuana use can lead to extensive airway injury and alterations in the structure and function of alveolar macrophages, potentially predisposing to pulmonary infection and respiratory cancer. Crack cocaine use can lead to a variety of acute pulmonary complications, including severe exacerbations of asthma and an acute lung injury syndrome associated with a broad spectrum of histopathologic changes ("crack lung"). Habitual cocaine smoking may also produce more subtle long-term pulmonary consequences due to chronic alveolar epithelial and microvascular lung injury. Heroin inhalation can induce severe and even fatal exacerbations of asthma. Pulmonary consequences of inhaled amyl and butyl nitrites, crystalline methamphetamine (ice), and phencyclidine have been less well documented.     

Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment

Pulmonary complications occur in 40% to 60% of recipients of bone marrow trans-plants, account for more than 90% of mortality, and develop during identifiable phases. Phase 1 (Days 1-30) includes pulmonary edema; diffuse alveolar hemorrhage; and various bacterial, fungal, and viral infections; Phase 2 (Days 31-100) usually requires a distinction between cytomegalovirus pneumonitis and idiopathic pneumonia syndrome; and Phase 3 (Day 100+) includes complications that are due to chronic graft-versus-host disease and associated bronchiolitis obliterans. The spectrum of pulmonary complications has been influenced by changes in transplantation technique, prophylactic treatment for infections, and the use of new chemotherapeutic agents that contribute to lung injury. Nonetheless, infections remain a leading cause of morbidity and mortality. The most serious complications result in respiratory failure, for which the prognosis has not improved significantly over the last 2 decades. In this article, we describe our algorithmic approach to the diagnosis and management of these complications.     

Nonfatal pulmonary edema after "freebase" cocaine smoking

Pulmonary edema is known to develop in users of heroin and methadone. Its association with cocaine use is usually a postmortem finding. There has been only 1 report of pulmonary edema being diagnosed clinically after cocaine use. In that case the cocaine was used intravenously, and death occurred within 3 h after the onset of symptoms. Here we describe a patient who developed acute pulmonary edema after smoking "freebase" cocaine. The pulmonary edema resolved spontaneously within 72 h. The cause of the acute reversible pulmonary edema was probably related to both pressure- and permeability-related changes.     

Bronchiolar disorders

Bronchiolar abnormalities are relatively common and occur in a variety of clinical settings. Various histopathologic patterns of bronchiolar injury have been described and have led to confusing nomenclature with redundant and overlapping terms. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Herein, we present a scheme separating (1) those disorders in which the bronchiolar disease is the predominant abnormality (primary bronchiolar disorders) from (2) parenchymal disorders with prominent bronchiolar involvement and (3) bronchiolar involvement in large airway diseases. Primary bronchiolar disorders include constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans), acute bronchiolitis, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust airway disease, follicular bronchiolitis, and a few other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia), and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical relevance of a bronchiolar lesion is best determined by identifying the underlying histopathologic pattern and assessing the correlative clinico-physiologic-radiologic context.     

Crack lung: an acute pulmonary syndrome with a spectrum of clinical and histopathologic findings

In this report, we review the hospital course of four patients who presented with an acute pulmonary syndrome after inhaling freebase cocaine and compare them with previously described case reports. Two patients had prolonged inflammatory pulmonary injury associated with fever, hypoxemia, hemoptysis, respiratory failure, and diffuse alveolar infiltrates. Lung tissue specimens from both patients revealed diffuse alveolar damage, alveolar hemorrhage, and interstitial and intraalveolar inflammatory cell infiltration notable for the prominence of eosinophils. Immunofluorescent staining performed on one of the biopsy specimens showed a striking deposition of IgE in both lymphocytes and alveolar macrophages. Both patients were treated with systemic corticosteroids and rapidly improved. In contrast, two patients presented acutely with diffuse pulmonary alveolar infiltrates associated with dyspnea and hypoxemia, but without fever, and within 36 h of discontinuing cocaine their pulmonary infiltrates and symptoms had spontaneously resolved. Our report further supports the finding that an acute pulmonary syndrome can occur after inhalation of freebase cocaine. Furthermore, the lung injury may respond to systemic corticosteroid therapy when it is associated with a prominent inflammatory cell infiltration.     

Bronchopulmonary disease in drug abusers

Drug abuse is a growing problem in industrialized countries, opening the way to new diseases of the respiratory tract. It has been demonstrated that regular inhalation of cannabis has the same consequences as tobacco smoking. The same cannot be said for other drugs. Cocaine, amphetamines or crack expose the patient to particular toxic effects: in addition to barotrauma related to the administration route, syndromes of acute respiratory distress have been described. These result either from bronchial reactions, asthma exacerbation or eosinophil bronchopneumonia, or alveolar involvement: intra-alveolar bleeding, pulmonary edema or organized pneumonia. Respiratory complications induced by opiates, often used in injections, are related to central alveolar hypoventilation and/or the development of injury from pulmonary edema or pneumonia. The pathophysiology of these lesions is not perfectly understood. Besides these specific conditions, infection is a major problem in drug abusers, irrespective of the drug: bacterial pneumonia, tuberculosis, HIV infection are much more frequent in this high-risk group. Finally repeated intravenous injections of various drugs designed for oral intake can lead to severe complications such as pulmonary hypertension or toxic interstitial lung disease. Summarizing, respiratory diseases in drug abuses can take on a wide range of quite complex presentations. Occasional or regular use of illicit drugs can lead, not exceptionally, to severe respiratory complications requiring rapid management. Knowledge of the principal complications and the appropriate diagnostic procedures is indispensable.     

Respiratory effects of cocaine "freebasing" among habitual users of marijuana with or without tobacco

Use of cocaine by smoking its alkaline precursor ("freebasing") has become increasingly prevalent. Recent studies of small numbers of cocaine users suggest that freebasing frequently causes cough, dyspnea, and abnormalities in diffusing capacity (DCO), although these findings could have been due to concomitant use of other drugs. We therefore evaluated the relationship between cocaine use by freebasing and chronic respiratory symptoms and lung dysfunction in a large sample of habitual smokers of marijuana with or without tobacco who denied intravenous drug abuse. The findings suggested that, among habitual marijuana smokers, "moderate" cocaine smoking damaged both large and small airways, as reflected by functional changes that were independent of concomitant marijuana use and appeared to be synergistic with the effects of tobacco. On the other hand, no adverse influence of cocaine smoking on the pulmonary microcirculation was demonstrated in our sample of freebase users.     

High-Resolution Computed Tomographic Findings of Cocaine-Induced Pulmonary Disease: A State of the Art Review

Cocaine is the most commonly used illicit drug among patients presenting at hospital emergency departments and the most frequent cause of drug-related deaths reported by medical examiners. Various respiratory problems temporally associated with cocaine use have been reported. Acute and chronic uses also are responsible for lung complications, such as pulmonary edema, alveolar hemorrhage, pulmonary hypertension, organizing pneumonia, emphysema, barotrauma, infection, cancer, eosinophilic disease, and aspiration pneumonia. Although most imaging findings are nonspecific, they may raise suspicion of a cocaine-related etiology when considered together with patients’ profiles and medical histories. This literature review describes cocaine-induced diseases with pulmonary involvement, with an emphasis on high-resolution chest computed tomographic findings and patterns.     

Significant pulmonary toxicity associated with interferon and ribavirin therapy for hepatitis C

OBJECTIVE: The aim of this study was to analyze the clinical presentation and outcomes of significant pulmonary toxicity associated with interferon and ribavirin. METHODS: We conducted a retrospective review of patients enrolled in four clinical trials at three sites, two academic medical centers and one community practice, and reviewed the literature. RESULTS: Four patients, while on therapy with interferon a and ribavirin for chronic hepatitis C, developed significant pulmonary signs and symptoms. Further workup, which included lung biopsy in three, revealed bronchiolitis obliterans organizing pneumonia in two, and interstitial pneumonitis in two other cases. There were no other predisposing factors for lung disease identified. Resolution of symptoms occurred in all patients upon discontinuation of interferon and ribavirin, with or without corticosteroid therapy. One of the patients developed pulmonary complications while on a clinical trial of pegylated interferon and represents the first reported case associated with the use of long-acting interferon in chronic hepatitis C infection. CONCLUSIONS: A spectrum of significant pulmonary toxicity, including bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis, can occur with interferon or pegylated interferon in combination with ribavirin. Though pulmonary toxicity of interferon is well known, these cases represent the first cases reported in the literature with combination therapy. It is likely that pulmonary toxicity may not be investigated in patients on combination therapy because of the frequent pulmonary symptoms with ribavirin. Though usually reversible, at least one case has required long-term steroids with inadequate resolution. Though pulmonary toxicity is rare, symptoms which are more than mild or progressive in nature should likely be investigated.     

Pulmonary edema after freebase cocaine smoking--not due to an adulterant

A case of pulmonary edema following smoking freebase cocaine is described. We did not clearly establish the mechanism, but this case is unique since adulterants and contaminants were excluded unlike all previously reported patients.     

Pulmonary disease due to antirheumatic agents

Drug-induced lung disease presents several diagnostic and therapeutic problems to the clinician. This is especially true in the case of lung disease associated with antirheumatic agents in which pulmonary disease may be due to the underlying disorder. Unfortunately, no specific markers exist to differentiate drug-induced lung disease from other pathologic processes. In addition, the numerous drugs often used simultaneously or in close sequence in rheumatic disorders make assignment of toxicity to a specific agent difficult. Six groups of drugs used as anti-inflammatory/antirheumatic agents have been discussed in association with pulmonary damage penicillamine, gold, methotrexate, salicylates, NSAIDs, and colchicine. The major clinical syndromes ascribed to these drugs include hypersensitivity pneumonitis and chronic alveolitis/fibrosis (penicillamine, gold, methotrexate, NSAIDs), pulmonary-renal syndrome (penicillamine), bronchiolitis obliterans (penicillamine, gold), and noncardiogenic pulmonary edema (salicylates, colchicine). Unfortunately, treatment options remain limited. Withdrawal of the offending drug and supportive care are the mainstays of therapy. In cases in which active inflammation causes significant derangement of gas exchange, corticosteroids are warranted. More aggressive management using immunosuppressive drugs has been recommended in cases of refractory PABO and PAGS, but these recommendations are at present based only on isolated case reports.     

Gut microecological regulation on bronchiolitis and asthma in children: A review

Introduction

Asthma and bronchiolitis in children are considered common clinical problems associated with gut microbiota. However, the exact relationship between gut microbiota and the above-mentioned diseases remains unclear. Here, we discussed recent advances in understanding the potential mechanism underlying immune regulation of gut microbiota on asthma and bronchiolitis in children as well as the role of the gut–lung axis.

Methods

We retrieved and assessed all relevant original articles related to gut microbiota, airway inflammation-induced wheezing in children, and gut–lung axis studies from databases that have been published so far, including PubMed/MEDLINE, Scopus, Google Scholar, China National Knowledge Infrastructure (CNKI) and the Wanfang Database.

Results

The infant period is critical for the development of gut microbiota, which can be influenced by gestational age, delivery mode, antibiotic exposure and feeding mode. The gut microbiota in children with asthma and bronchiolitis is significantly distinct from those in healthy subjects. Gut microbiota dysbiosis is implicated in asthma and bronchiolitis in children. The presence of intestinal disturbances in lung diseases highlights the importance of the gut–lung axis.

Conclusion

Gut microbiota dysbiosis potentially increases the risk of asthma and bronchiolitis in children. Moreover, a deeper understanding of the gut–lung axis with regard to the gut microbiota of children with respiratory diseases could contribute to clinical practice for pulmonary diseases.     

A hitherto unreported pulmonary complication in an IV heroin user

IV heroin use is associated with several well-described complications, including noncardiogenic pulmonary edema, aspiration pneumonitis, ARDS, pneumonia, lung abscess, septic pulmonary emboli, and atelectasis. Foreign-body granulomatosis may develop when drug users inject solutions containing crushed oral tablets in which talc is used as filler and can be complicated by pulmonary fibrosis. The effects are distinct from pulmonary edema, which may occur acutely with heroin injection. We describe the case of a young female patient who was an IV heroin user who also smoked cigarettes, and presented with progressive dyspnea, hypoxia, and bilateral lung infiltrates. The final pathologic diagnosis in this case was one that had not been previously reported in IV heroin users.     

Rheumatoid arthritis and cryptogenic organising pneumonitis

We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.     

Medikamenteninduzierte Lungenerkrankungen

Adverse effects of drug therapy may affect all compartments of the respiratory system and simulate a wide variety of bronchopulmonary disorders. The spectrum of drug induced lung and bronchial diseases include simple cough, bronchial obstruction, and obstructive bronchiolitis. Lung parenchyma may be affected by alveolitis/pneumonia or lung fibrosis. Further damage pattern are noncardiac pulmonary edema, diffuse alveolar damage or diffuse alveolar hemorrhage. Drugs are potential causes of eosinophilic lung diseases, pulmonary vascular disorders as well as pleural affections. These side effects rarely have pathognomonic features. Therefore they are relevant differential diagnoses of genuine pulmonary diseases. Diagnostics is mainly based on the verification of a compatible disease pattern, exclusion of differential diagnoses, assessment of the temporal relationship and the consequences of drug abstention. Reexposure is rarely indicated. Strict elimination of the responsible drugs is the most important therapeutic measure. Additional drug therapy, mostly with glucocorticosteroids, may be indicated.     

Minocycline-induced neutrophilic alveolitis?

A 53-year-old man was treated for hypoxic pneumonia. Alveolar lavage revealed neutrophilic alveolitis and search for an infectious agent was negative. Lung biopsy revealed discrete endo-alveolar edema and polymorphous infiltration in moderately thickened alveolar walls. After 17 days, an ineffective antibiotic regimen was replaced by corticosteroids. Clinical and radiological signs improved in a few days and pneumonia did not recur after corticosteroid withdrawal. The most likely causal agent was minocycline which the patient had received for two Years for the treatment of rhinophyma. Minocycline had been interrupted several weeks when the pulmonary disorder developed after re-introduction of minocycline. Different clinical manifestations of minocycline-induced lung disease have been described including eosinophilic pneumopathy, bronchiolitis obliterans with organized pneumonitis, and hypersensitivity pneumonitis. There has only been one report of polymorphonuclear neutrophils observed in the lavage fluid.     

Is bronchiolitis in infancy an antecedent of chronic lung disease in adolescence and adulthood?

Acute bronchiolitis in infancy appears to be associated with persistence of wheezing or subsequent asthma in later life. Chest imaging techniques have demonstrated persistent structural lung damage such as atelectasis, bronchiectasis, and obliterative bronchiolitis among survivors of the more severe forms of bronchiolitis. In addition, in a significant number of survivors without demonstrable structural damage, pulmonary function studies have revealed a spectrum of disturbances including air-trapping, reduced air flow at low lung volumes, hypoxemia (all indicating disease in the small airways), and bronchial hyperreactivity. However, it has not yet been proven definitively whether the relationship between severe bronchiolitis in infancy and chronic obstructive lung disease is causal or noncausal. Further prospective clinical studies are needed to resolve this question.     

Pulmonary manifestations of systemic lupus erythematosus: review of twelve cases of acute lupus pneumonitis.

Acute lupus pneumonitis was the presenting manifestation of systemic lupus erythematosus in six of 12 cases in this series. The clinical picture was characterized by severe dyspnea, tachypnea, fever and arterial hypoxemia. Radiographic findings included an acinar filling pattern which was invariably found in the lower lobes and was bilateral in 10 of the cases. Studies failed to reveal evidence of infection as a cause of the acute pulmonary infiltrates. All patients were treated with oxygen and corticosteroids; seven received azathioprine. Six patients survived and are clinically well 14 months to four years following their acute illness. Three of these patients have residual interstitial infiltrates with persistent pulmonary function test abnormalities indicating progression to chronic interstitial pneumonitis. Histologic sections of the lungs available from four patients revealed hyaline membranes and interstitial edema (four cases), acute alveolitis (two cases), arteriolar thrombosis (one case) and a prominent lymphocytic interstitial pneumonitis with organizing bronchiolitis (one case).     

Pulmonary complications of treatment with pegylated interferon for hepatitis C infection-Two case reports

Pegylated interferon (Peg-IFN) in combination with ribavirin is the standard of care in the treatment of chronic hepatitis C (HCV). Peg-IFN is known to have a number of side effects but severe respiratory complications are uncommon. We report two cases, one of Peg-IFN induced interstitial pneumonitis (IP) and the other of bronchiolitis obliterans organising pneumonia (BOOP) in patients with chronic hepatitis C infection. In general, respiratory complications of Peg-IFN are mild and resolve with withdrawal of Peg-IFN. However, as illustrated in our first case fatal interstitial pneumonitis can occur. We present a review of the available literature on Peg-IFN induced lung toxicity. In conclusion, pulmonary toxicity with Peg-IFN is rare but fatality can occur. We highlight the importance of maintaining a high index of suspicion for early diagnosis and prompt treatment, which includes withdrawal of Peg-IFN and consideration of corticosteroid treatment.