• Valérie Siroux, Anne Boudier, Maïa Dolgopoloff, Sébastien Chanoine, Jean Bousquet, Frederic Gormand, Jocelyne Just, Nicole Le Moual, Rachel Nadif, Christophe Pison, Raphaëlle Varraso, Regis Matran, and Isabelle Pin.
• Université Grenoble Alpes, IAB, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France; Inserm, IAB, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France; CHU de Grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France. Electronic address: Valerie.siroux@ujf-grenoble.fr.
• J. Allergy Clin. Immunol. 2016 Jun 1; 137 (6): 1709-1716.e6.

BackgroundWhether small-airway obstruction contributes to the long-term evolution of asthma remains unknown.ObjectivesOur aim was to assess whether the level of forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1.MethodsWe studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF25-75 decreased by 10% of predicted value.ResultsA reduced level of FEF25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV1 and in participants with FEV1 of greater than 80% of predicted value. A reduced FEF25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness (P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation.ConclusionOur analysis is the first to suggest that small-airway obstruction, as assessed based on FEF25-75, might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways.Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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