title: Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.
abstract: Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93) and after (n = 78) methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw), reflecting large airway volume, and the slope of the alveolar capnogram (slope3), an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20). Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66) and Slope3 (SC = 0.35). By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8) but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways.
authors.affiliation: INSERM UMR 1152, Labex Inflamex, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.|Assistance-Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Service de Physiologie-Explorations Fonctionnelles, DHU FIRE, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Plantier
authors.affiliation: Hôpital Bretonneau, Service de Pneumologie, Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.affiliation: INSERM U955, Créteil, France.|Université Paris-Est, Créteil, France.|Assistance-Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Physiologie-Explorations Fonctionnelles, Créteil, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.affiliation: INSERM UMR 1152, Labex Inflamex, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.|Assistance-Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Service de Pneumologie A, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Taillé
authors.affiliation: Assistance-Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie-Explorations Fonctionnelles, Paris, France.|Université Paris Descartes, Paris, France.|INSERM CIC Plurithématique 9201, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Delclaux
mesh_terms: D000328:Adult; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D008875:Middle Aged; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride