Forty healthy young subjects, ages 20 to 49 yr, underwent videobronchoscopy, mucosal biopsy, and bronchial lavage to evaluate the airway inflammation produced by habitual smoking of marijuana and/or tobacco. Videotapes were graded in a blinded manner for central airway erythema, edema, and airway secretions using a modified visual bronchitis index. The bronchitis index scores were significantly higher in marijuana smokers (MS), tobacco smokers (TS), and in combined marijuana/tobacco smokers (MTS), than in nonsmokers (NS). As a pathologic correlate, mucosal biopsies were evaluated for the presence of vascular hyperplasia, submucosal edema, inflammatory cell infiltrates, and goblet cell hyperplasia. Biopsies were positive for two of these criteria in 97% of all smokers and for three criteria in 72%. By contrast, none of the biopsies from NS exhibited greater than one positive finding. Finally, as a measure of distal airway inflammation, neutrophil counts and interleukin-8 (IL-8) concentrations were determined in bronchial lavage fluid. The percentage of neutrophils correlated with IL-8 levels and exceeded 20% in 0 of 10 NS, 1 of 9 MS, 2 of 9 TS, and 5 of 10 MTS. We conclude that regular smoking of marijuana by young adults is associated with significant airway inflammation that is similar in frequency, type, and magnitude to that observed in the lungs of tobacco smokers.
Abstract-Patients with obstructive and restrictive ventilatory abnormalities suffer from exercise intolerance and dyspnea. Breathing pattern components (volume, flow, and timing) during incremental exercise may provide further insight in the role played by dynamic hyperinflation in the genesis of dyspnea. This study analyzed the breathing patterns of patients with obstructive and restrictive ventilatory abnormalities during incremental exercise. It also explored breathing pattern components with dyspnea at maximum oxygen uptake (VO 2 max). Twenty patients, thirteen obstructive patients (forced expiratory volume 38% ± 13% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 39 ± 8%), and seven restrictive patients (forced vital capacity 55 ± 16% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 84% ± 11%) performed symptom-limited incremental exercise tests on a cycle ergometer with breath-by-breath determination of ventilation and gas exchange parameters. Breathing patterns were analyzed at baseline, 20, 40, 60, 80, and 100 percent of VO 2 max. Dyspnea was measured at end-exercise with a 100 mm visual analogue scale. The timing ratio of inspiratory to expiratory time (T I /T E ) and the flow ratio of inspiratory flow to expiratory flow ratio ( I / E ) were different (p < 0.008) between obstructive and restrictive patients at all exercise intensity levels. The timing components of expiratory time (T E ) and inspiratory time to total time (T I T TOT ) were significantly different (p < 0.008) at baseline and maximum exercise. Dyspnea scores were not significantly different. For obstructive patients, correlations were noted between T I /T E , I / E , T I T TOT and dyspnea (p < 0.05). Breathing pattern-timing components, specifically T I /T E , in patients with obstructive and restrictive ventilatory abnormalities during exercise provided further insight into the pathophysiology of the two conditions and the contribution of dynamic hyperinflation to dyspnea.
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