Regional airflow obstruction after bronchoconstriction and subsequent bronchodilation in subjects without pulmonary disease.

Some subjects with asthma have ventilation defects that are resistant to bronchodilator therapy, and it is thought that these resistant defects may be due to ongoing inflammation or chronic airway remodeling. However, it is unclear whether regional obstruction due to bronchospasm alone persists after bronchodilator therapy. To investigate this, six young, healthy subjects, in whom inflammation and remodeling were assumed to be absent, were bronchoconstricted with a PC20 [the concentration of methacholine that elicits a 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine and subsequently bronchodilated with a standard dose of albuterol on three separate occasions. Specific ventilation imaging, a proton MRI technique, was used to spatially map specific ventilation across 80% of each subject's right lung in each condition. The ratio between regional specific ventilation at baseline and after intervention was used to classify areas that had constricted. After albuterol rescue from methacholine bronchoconstriction, 12% (SD 9) of the lung was classified as constricted. Of the 12% of lung units that were classified as constricted after albuterol, approximately half [7% (SD 7)] had constricted after methacholine and failed to recover, whereas half [6% (SD 4)] had remained open after methacholine but became constricted after albuterol. The incomplete regional recovery was not reflected in the subjects' FEV1 measurements, which did not decrease from baseline (P = 0.97), nor was it detectable as an increase in specific ventilation heterogeneity (P = 0.78).NEW & NOTEWORTHY In normal subjects bronchoconstricted with methacholine and subsequently treated with albuterol, not all regions of the healthy lung returned to their prebronchoconstricted specific ventilation after albuterol, despite full recovery of integrative lung indexes (forced expiratory volume in 1 s and specific ventilation heterogeneity). The regions that remained bronchoconstricted following albuterol were those with the highest specific ventilation at baseline, which suggests that they may have received the highest methacholine dose.

Spatial persistence of reduced specific ventilation following methacholine challenge in the healthy human lung.

Specific ventilation imaging was used to identify regions of the healthy lung (6 supine subjects, ages 21-41 yr, 3 men) that experienced a fall in specific ventilation following inhalation of methacholine. This test was repeated 1 wk later and 3 mo later to test for spatial recurrence. Our data showed that 53% confidence interval (CI; 46%, 59%) of volume elements that constricted during one methacholine challenge did so again in another and that this quantity did not vary with time; 46% CI (28%, 64%) recurred 1 wk later, and 56% CI (51%, 61%) recurred 3 mo later. Previous constriction was a strong predictor for future constriction. Volume elements that constricted during one challenge were 7.7 CI (5.2, 10.2) times more likely than nonconstricted elements to constrict in a second challenge, regardless of whether the second episode was 1 wk [7.7 CI (2.9, 12.4)] or 3 mo [7.7 CI (4.6, 10.8)] later. Furthermore, posterior lung elements were more likely to constrict following methacholine than anterior lung elements (volume fraction 0.43 ± 0.22 posterior vs. 0.10 ± 0.03 anterior; P = 0.005), and basal elements that constricted were more likely than their apical counterparts to do so persistently through all three trials (volume fraction 0.14 ± 0.04 basal vs. 0.04 ± 0.04 apical; P = 0.003). Taken together, this evidence suggests a physiological predisposition toward constriction in some lung elements, especially those located in the posterior and basal lung when the subject is supine. NEW & NOTEWORTHY The spatial pattern of bronchoconstriction following methacholine is persistent over time in healthy individuals, in whom chronic inflammation and airway remodeling are assumed to be absent. This suggests that regional lung inflation and airway structure may play dominant roles in determining the spatial pattern of methacholine bronchoconstriction.