Published ahead of print on March 22, 2007, doi:10.1164/rccm.200612-1814OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200612-1814OC
Bronchial Inflammation and Airway Responses to Deep Inspiration in Asthma and Chronic Obstructive Pulmonary Disease1 Department of Pulmonology, Leiden University Medical Center, Leiden. The Netherlands; 2 Department of Pulmonology, Medical Center Alkmaar, Alkmaar, The Netherlands; 3 Department of Pediatrics, Erasmus University Medical Center–Sophia Children's Hospital, Rotterdam, The Netherlands; 4 Department of Pathology, Saõ Paulo University Medical School, Saõ Paulo, Brazil; and 5 Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Correspondence and requests for reprints should be addressed to Annelies M. Slats, M.D., Leiden University Medical Center, Department of Pulmonology (C2-P-62), P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: a.m.slats{at}lumc.nl Rationale: Deep inspirations provide physiologic protection against airway narrowing in healthy subjects, which is impaired in asthma and chronic obstructive pulmonary disease (COPD). Airway inflammation has been suggested to alter airway mechanics during deep inspiration. Objectives: We tested the hypothesis that the number of bronchial inflammatory cells is related to deep inspiration–induced bronchodilation in asthma and COPD. Methods: In a cross-sectional study, three modified methacholine challenges were performed in 13 patients with mild, persistent asthma, 12 patients with mild to moderate COPD, and 12 healthy control subjects. Measurements and Main Results: After a 20-minute period of deep inspiration avoidance, inhalation of methacholine was followed by either one or five deep inspirations, or preceded by five deep inspirations. The response to deep inspiration was measured by forced oscillation technique. Inflammatory cells were counted within the lamina propria and airway smooth muscle area in bronchial biopsies of patients with asthma and COPD. The reduction in expiratory resistance by one and five deep inspirations was significantly less in asthma (mean change ± SD: –0.5 ± 0.8 and –0.9 ± 1.0 cm H2O/L/s, respectively) and COPD (+0.2 ± 1.1 and +0.4 ± 1.0 cm H2O/L/s, respectively) as compared with healthy subjects (–1.5 ± 1.3 and –2.0 ± 1.2 cm H2O/L/s, respectively; p = 0.05 and p = 0.001, respectively). In asthma, this was related to an increase in mast cell numbers within the airway smooth muscle area (r = 0.73; p = 0.03), and in CD4+ lymphocytes in the lamina propria (r = 0.61; p = 0.04). Conclusions: Inflammation in the airway smooth muscle bundles and submucosa of bronchial biopsies is positively associated with impaired airway mechanics during deep inspiration in asthma, but not in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT OO279136).
Key Words: airway smooth muscle • deep breath • forced oscillation technique • mast cells • resistance of the respiratory system
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