title: Ventilation defect formation in healthy and asthma subjects is determined by lung inflation.
abstract: BACKGROUND
  Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion.
  
  
  OBJECTIVE
  We studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma.
  
  
  METHODS
  Spirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous ¹³NN-saline positron emission tomography were measured before and after a challenge with nebulized methacholine. Vdefs were defined as regions with elevated residual ¹³NN after a period of washout. The average location, ventilation, volume, and fractional gas content of the Vdefs, relative to those of the rest of the lung, were calculated for both groups.
  
  
  RESULTS
  Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed Vdefs. These Vdefs tended to form in regions that, at baseline, had a lower degree of lung inflation and, in healthy subjects, tended to occur in more dependent locations than in subjects with asthma.
  
  
  CONCLUSIONS
  The formation of Vdefs is determined by the state of inflation prior to bronchoconstriction.
authors.affiliation: Department of Medicine-Pulmonary and Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. rsharris@mgh.harvard.edu
authors.forename: R Scott
authors.initials: RS
authors.lastname: Harris
authors.forename: Hanae
authors.initials: H
authors.lastname: Fujii-Rios
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.forename: Guido
authors.initials: G
authors.lastname: Musch
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Vidal Melo
authors.forename: José G
authors.initials: JG
authors.lastname: Venegas
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011659:Pulmonary Gas Exchange; D012123:Pulmonary Ventilation / Q000502:physiology*; D011859:Radiography; D012119:Respiration; D013147:Spirometry; D055815:Young Adult