title: Clinical significance of small airway obstruction markers in patients with asthma.
abstract: BACKGROUND
  The role of small airway obstruction in the clinical expression of asthma is incompletely understood.
  
  
  OBJECTIVE
  We tested the hypotheses that markers of small airway obstruction are associated with (i) increased asthma severity, (ii) impaired asthma control and quality of life and (iii) frequent exacerbations.
  
  
  METHODS
  Seventy-four adults with asthma and 18 healthy control subjects underwent impulse oscillometry (IOS), multiple breath inert gas washout (MBW), body plethysmography, single-breath determination of carbon monoxide uptake and spirometry. Patients completed the six-point Asthma Control Questionnaire (ACQ-6) and standardized Asthma Quality of Life Questionnaire [AQLQ(S)]. Asthma severity was classified according to the Global Initiative for Asthma (GINA) treatment steps.
  
  
  RESULTS
  The putative small airway obstruction markers Sacin , resistance at 5 Hz minus resistance at 20 Hz (R5-R20) and reactance area (AX) were not independently associated with asthma severity, control, quality of life or exacerbations. In contrast, markers of total (R5) and mean airway resistance of large and small airways (R20) were significantly higher in the severe asthma group compared with the mild-moderate group (0.47 vs. 0.37, P < 0.05 for R5; 0.39 vs. 0.31, P < 0.01 for R20). The strongest independent contributors to ACQ-6 score were R20 and forced expiratory volume in one second (% pred.), and the strongest independent contributors to AQLQ(S) score were R20 and forced vital capacity (% pred.). A history of one or more exacerbations within the previous year was independently associated with R20.
  
  
  CONCLUSIONS
  Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.
authors.affiliation: Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Gonem
authors.forename: S
authors.initials: S
authors.lastname: Natarajan
authors.forename: D
authors.initials: D
authors.lastname: Desai
authors.forename: S
authors.initials: S
authors.lastname: Corkill
authors.forename: A
authors.initials: A
authors.lastname: Singapuri
authors.forename: P
authors.initials: P
authors.lastname: Bradding
authors.forename: P
authors.initials: P
authors.lastname: Gustafsson
authors.forename: R
authors.initials: R
authors.lastname: Costanza
authors.forename: R
authors.initials: R
authors.lastname: Kajekar
authors.forename: H
authors.initials: H
authors.lastname: Parmar
authors.forename: C E
authors.initials: CE
authors.lastname: Brightling
authors.forename: S
authors.initials: S
authors.lastname: Siddiqui
mesh_terms: D000402:Airway Obstruction / Q000503:physiopathology*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index
keywords: asthma; impulse oscillometry; multiple breath washout; small airway disease