Published ahead of print on March 22, 2007, doi:10.1164/rccm.200612-1814OC Am. J. Respir. Crit. Care Med., Volume 176, Number 2, July 2007, 121-128 A more recent version of this article appeared on July 15, 2007
Submitted on December 15, 2006 Bronchial Inflammation and Airway Responses to Deep Inspiration in Asthma and COPDAnnelies M Slats1*,1 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, Sao Paulo University Medical School, Sao Paulo, Brazil, 5 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands; Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands * To whom correspondence should be addressed. E-mail: a.m.slats{at}lumc.nl.
Rationale; Deep inspirations provide physiological protection against airway narrowing in healthy subjects, which is impaired in asthma and COPD. Airway inflammation has been suggested to alter airway mechanics during deep inspiration. Objective; We tested the hypothesis that the number of bronchial inflammatory cells is related to deep inspiration-induced bronchodilation in asthma and COPD. Methods and measurements; In a cross-sectional study three modified methacholine challenges were performed in 13 mild persistent asthmatics, 12 mild to moderate COPD patients and 12 healthy control subjects. 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. Main Results; The reduction in expiratory resistance by one and five deep inspirations was significantly less in asthma (mean change±SD -0.5±0.8 cmH2O/L/s and -0.9±1.0 cmH2O/L/s) and COPD (+0.2±1.1 cmH2O/L/s and +0.4±1.0 cmH2O/L/s), as compared to healthy subjects (-1.5±1.3 cmH2O/L/s and -2.0±1.2 cmH2O/L/s, 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=0.72, 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. www.clinicaltrials.gov id: NCT00279136 Key words: Mast cells, airway smooth muscle, resistance of the respiratory system, forced oscillation technique, deep breath.
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