Relationship between airway pathophysiology and airway inflammation in older asthmatics

Abstract

Background and objective: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR).

Methods: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO).

Results: Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P < 0.001), but not with neutrophils or neutrophil mediators. The Closing Index correlated with total sputum neutrophils (r = 0.66, P = 0.005), neutrophil elastase, matrix metalloproteinase-9 and interleukin-8 (all P < 0.05). Further, FEV1 /FVC and residual volume/total lung capacity at rest correlated with neutrophil elastase (r = -0.46 and 0.66 respectively, P < 0.05) but not with eosinophils or eNO.

Conclusions: In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during bronchoconstriction. The clinical implications of these findings remain to be determined.

Keywords: airway closure; airway hyper responsiveness; airway inflammation; asthma; elderly.