Contribution of peripheral airway function to changes in FEV1/FVC and RV/TLC with aging.

Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (Sacin) and conducting (Scond) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1/FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23-89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1/FVC (R2 = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R2 = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1/FVC was strongest in the older group (R2 = 0.20, P = 0.003) but markedly weaker in the younger group (R2 = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R2 = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1/FVC or RV/TLC. Changes in FEV1/FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1/FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging.

Cut-points for response to mannitol challenges using the forced oscillation technique.

The forced oscillation technique (FOT) can be used to determine airway hyperresponsiveness, but the cut-points for changes in respiratory system conductance (Grs) and reactance (Xrs) that define a positive mannitol challenge are not known. Furthermore, the effects of changes in lung volume on these cut-points or on the repeatability of the test are unknown. In 15 non-asthmatic and 52 asthmatic subjects, response to mannitol challenge was measured by Grs and Xrs, using FOT, and by FEV(1). The FOT variables were adjusted for inspiratory capacity (IC) at each dose. Dose response slope (DRS) was used in receiver operator characteristic (ROC) analysis to compare the ability of adjusted and unadjusted DRSGrs and DRSXrs to detect a positive challenge, defined as PD(15)FEV(1) ≤635 mg mannitol. Mannitol challenges were positive in 32 asthmatic and 2 non-asthmatic subjects. Both DRSGrs and DRSXrs detected positive challenges (p < 0.0001 for both), and this was not altered by adjustment for IC for either DRSGrs (p = 0.21) or DRSXrs (p = 0.90). FOT cut-points for a positive challenge were 27% fall in Grs or 0.93 cm H(2)O/L/s decrease in Xrs at 635 mg. Repeatability of DRSGrs (±2.01 doubling doses) and DRSXrs (±1.95dd) was comparable with DRSFEV(1) (±1.67dd) and was not improved by adjustment for IC. Grs and Xrs, measured by FOT, provide a sensitive, repeatable measure of response to mannitol challenge. Adjusting for lung volume does not alter the ability of these variables to detect a positive response or the repeatability of the measurement.