Airway Closure and its Relation to Neutrophilic and Eosinophilic Inflammation in Acute Asthma

摘要

Enhanced airway closure has been associated with recurrent exacerbations in patients with severe asthma (in't Veen, AJRCCM, 2000). We hypothesized that airway closure would also be evident in patients presenting to the Emergency Department (ED) with an acute exacerbation of asthma. In an ongoing study, we are measuring lung function (spirometry, respiratory system resistance [Rrs] and elastance [Ers]) and induced sputum cell counts from such patients. Patients are discharged on inhaled fluticasone/salmeterol 500 |xg/50 μg BID and measurements are repeated approximately 4 weeks later. At presentation, data from 29 patients with acute asthma (11 male) have revealed decrements in lung function (FEV_1, FVC, FEVi/FVC) and predominant neutrophilic inflammation (57% neutrophils, 6% eosinophils). Over the subsequent 4 weeks, the percentage of neutrophils and eosinophils decreased slightly but not significantly, while lung function showed small, significant increases in FEVj (+20%) and FVC (+15%), but not FEV_1/ FVC (+5%). At presentation, Rrs was not significantly elevated, nor did it change significantly during the ED treatment period, but decreased slightly after treatment with albuterol at 4 weeks. At presentation, Ers was elevated, and decreased significantly after albuterol at 4 weeks. FEVi and FVC, but not FEVj/FVC, correlated with Ers (rho = -0.63, P < 0.05; -0.56, P < 0.01), but not Rrs. Eosinophils correlated with FEVi and FVC (-0.72, P = 0.02; -0.84, P < 0.01), but not with YEV1/ FVC, Rrs or Ers, while neutrophils correlated with Rrs only (0.77, P = 0.02). These data suggest that at presentation, an acute exacerbation of asthma is associated with substantial peripheral airway dysfunction including airway closure (reduced FVC, elevated Ers). Eosinophils reflect peripheral lung dysfunction, whereas neutrophils are associated with central airway dysfunction (Rrs). There is little improvement after 4 weeks of therapy. We speculate that the persistent inflammation that follows an acute exacerbation of asthma may result in an increased propensity for peripheral airway narrowing and closure leading to future exacerbations.