title: Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations.
abstract: BACKGROUND
  Severe exacerbations of asthma are periods of excess functional and pathological changes in the airways that have been proposed to induce airway remodeling.
  
  
  OBJECTIVE
  The objective of this study was to explore whether severe exacerbations are correlated with the decline in post-bronchodilator forced expiratory volume in 1 second (FEV1) and loss of bronchodilator reversibility (BDR).
  
  
  METHODS
  We examined the changes in FEV1 and BDR in 140 nonsmoking patients with well-controlled asthma at baseline and correlated these changes with the frequency of severe asthma exacerbations.
  
  
  RESULTS
  A 3-year follow-up assessment was completed in 128 patients. A total of 28 (21.9%) patients experienced at least 1 severe exacerbation with a mean rate of 0.16 year(-1). The exacerbation rate was significantly correlated with an annual rate of decline in FEV1 (ρ = 0.49, P < .0001). Both patients with 1 exacerbation and those with 2 or more exacerbations had greater declines in FEV1 than patients with no exacerbations (no exacerbation, 13.6 mL/year; 1 exacerbation, 41.3 mL/year; 2 or more exacerbations, 58.3 mL/year; P < .01 and P < .0001, respectively). The changes in BDR from baseline to the end of the study in patients who did or did not experience an exacerbation were -1.2% and 0.1%, respectively (P < .0005). The changes in BDR were significantly correlated with the annual rates of change in FEV1 (r = 0.40, P < .0001).
  
  
  CONCLUSIONS
  The occurrence of severe exacerbations of asthma is correlated with the progression of irreversible airflow limitation over time. This suggests that asthma exacerbations could have the long-term adverse consequences of structural and functional changes in the airways.
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address: kazmatsu@yamaguchi-u.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Oka
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Kuninobu
authors.initials: K
authors.lastname: Kanai
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hayata
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Akamatsu
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Akamatsu
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001993:Bronchodilator Agents; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000503:physiopathology
chemical_list: D001993:Bronchodilator Agents
keywords: Airway inflammation; Airway remodeling; Airway reversibility; Bronchodilator; Lung function