Bronchial inflammation and airway responses to deep inspiration in asthma and chronic obstructive pulmonary disease.
BACKGROUND
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.


OBJECTIVE
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.


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).
Slats
Annelies M
AM
Leiden University Medical Center, Department of Pulmonology (C2-P-62), P.O. Box 9600, 2300 RC Leiden, and Department of Pediatrics, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. a.m.slats@lumc.nl
Janssen
Kirsten
K
van Schadewijk
Annemarie
A
van der Plas
Dirk T
DT
Schot
Robert
R
van den Aardweg
Joost G
JG
de Jongste
Johan C
JC
Hiemstra
Pieter S
PS
Mauad
Thais
T
Rabe
Klaus F
KF
Sterk
Peter J
PJ
D000328:Adult; D000368:Aged; D000403:Airway Resistance / Q000502:physiology; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D001239:Inhalation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology* / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology