title: Disparity between proximal and distal airway reactivity during methacholine challenge.
abstract: There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV(1) change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R(5), R(20)) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5-20 Hz (R(5-20)) and reactance area (AX). R(5) varied widely during MCT (range -0.8 - 11.3 cmH(2)O/L/s) and correlated poorly with change in FEV(1) (r = 0.17). Changes in R(5) reflected changes in both R(20) and R(5-20) (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R(20) increased only 0.3 cmH(2)O/L/s, while R(5-20) increased 0.7 cmH(2)O/L/s for every 1cmH(2)O/L/s change in R(5,) indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV(1) change (<5%), while R(5) increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV(1) and R(20)) and distal airway heterogeneity (R(5-20) and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV(1). This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment.
authors.affiliation: André Cournand Pulmonary Physiology Laboratory, New York University School of Medicine, New York, New York 10016, USA. Segal@nyumc.org
authors.forename: Leopoldo N
authors.initials: LN
authors.lastname: Segal
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Goldring
authors.forename: Beno W
authors.initials: BW
authors.lastname: Oppenheimer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stabile
authors.forename: Joan
authors.initials: J
authors.lastname: Reibman
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weiden
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D008875:Middle Aged; D009991:Oscillometry; D012189:Retrospective Studies; D013147:Spirometry; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride