Effect of methacholine on peripheral lung mechanics and ventilation heterogeneity in asthma.
The forced oscillation technique (FOT) and multiple-breath nitrogen washout (MBNW) are noninvasive tests that are potentially sensitive to peripheral airways, with MBNW indexes being especially sensitive to heterogeneous changes in ventilation. The objective was to study methacholine-induced changes in the lung periphery of asthmatic patients and determine how changes in FOT variables of respiratory system reactance (Xrs) and resistance (Rrs) and frequency dependence of resistance (Rrs5-Rrs19) can be linked to changes in ventilation heterogeneity. The contributions of air trapping and airway closure, as extreme forms of heterogeneity, were also investigated. Xrs5, Rrs5, Rrs19, Rrs5-Rrs19, and inspiratory capacity (IC) were calculated from the FOT. Ventilation heterogeneity in acinar and conducting airways, and trapped gas (percent volume of trapped gas at functional residual capacity/vital capacity), were calculated from the MBNW. Measurements were repeated following methacholine. Methacholine-induced airway closure (percent change in forced vital capacity) and hyperinflation (change in IC) were also recorded. In 40 mild to moderate asthmatic patients, increase in Xrs5 after methacholine was predicted by increases in ventilation heterogeneity in acinar airways and forced vital capacity (r(2) = 0.37, P < 0.001), but had no correlation with ventilation heterogeneity in conducting airway increase or IC decrease. Increases in Rrs5 and Rrs5-Rrs19 after methacholine were not correlated with increases in ventilation heterogeneity, trapped gas, hyperinflation, or airway closure. Increased reactance in asthmatic patients after methacholine was indicative of heterogeneous changes in the lung periphery and airway closure. By contrast, increases in resistance and frequency dependence of resistance were not related to ventilation heterogeneity or airway closure and were more indicative of changes in central airway caliber than of heterogeneity.
Woolcock Institute of Medical Research, Glebe, Sydney, New South Wales, Australia. sue.downie@woolcock.org.au
Sue R
SR
Downie
Cheryl M
CM
Salome
Sylvia
S
Verbanck
Bruce R
BR
Thompson
Norbert
N
Berend
Gregory G
GG
King
D000293:Adolescent; D000328:Adult; D000368:Aged; D000403:Airway Resistance; D000704:Analysis of Variance; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D005260:Female; D005541:Forced Expiratory Volume; D005652:Functional Residual Capacity; D006801:Humans; D007320:Inspiratory Capacity; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D016210:Methacholine Chloride; D008875:Middle Aged; D009991:Oscillometry; D011237:Predictive Value of Tests; D012123:Pulmonary Ventilation; D015656:Respiratory Mechanics; D013147:Spirometry; D055815:Young Adult
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride