title: Forced midexpiratory flow between 25% and 75% of forced vital capacity is associated with long-term persistence of asthma and poor asthma outcomes.
abstract: Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown.
  
  
  
  Our 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.
  
  
  
  We 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.
  
  
  
  A 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.
  
  
  
  Our 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.
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Siroux
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Boudier
authors.affiliation: 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.
authors.forename: Maïa
authors.initials: M
authors.lastname: Dolgopoloff
authors.affiliation: 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Chanoine
authors.affiliation: Inserm U1168, VIMA (Aging and chronic diseases, Epidemiological and public health approaches), Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny-le-Bretonneux, France; University Hospital, Montpellier, and MeDALL (Mechanisms of the Development of Allergy, FP7), Montpellier, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.affiliation: CHU de Lyon, Pneumology Department, Lyon, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Gormand
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, Allergology Department, Paris, France; Université Paris 6 Pierre et Marie Curie, Paris, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Just
authors.affiliation: Inserm U1168, VIMA (Aging and chronic diseases, Epidemiological and public health approaches), Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny-le-Bretonneux, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Le Moual
authors.affiliation: Inserm U1168, VIMA (Aging and chronic diseases, Epidemiological and public health approaches), Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny-le-Bretonneux, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Nadif
authors.affiliation: Clinique Universitaire de Pneumologie, Pôle de Cancérologie, Médecine Aiguë et Communautaire, CHU Grenoble, Grenoble, France; Inserm 1055, Grenoble, France; Universite Joseph Fourier, Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pison
authors.affiliation: Inserm U1168, VIMA (Aging and chronic diseases, Epidemiological and public health approaches), Villejuif, France; Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny-le-Bretonneux, France.
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Varraso
authors.affiliation: Université Lille Nord de France, Lille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Matran
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pin
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000503:physiopathology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D063868:Patient Outcome Assessment; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D013147:Spirometry; D014797:Vital Capacity; D055815:Young Adult
keywords: Asthma; FEF(25-75); epidemiology; longitudinal; small airways