SLOW COMPARTMENT FEATURES AND GAS-EXCHANGE IMPAIRMENT IN MILD ASTHMA - EFFECTS OF BETA-AGONIST INHALATION

Static and dynamic lung volumes, arterial blood gases, alveolar ventil ation and ventilation-perfusion ((V) over dot(A)/(Q) over dot) relatio nships were studied in 14 mild asthmatic patients and in 7 normal subj ects (as controls) before and after fenoterol inhalation. Multiple nit rogen washout curves were analyzed by a bicompartmental distribution m odel, in order to assess the distribution of ventilation and (V) over dot(A)/(Q) over dot mismatch. At baseline, asthmatics showed mild airw ay obstruction and gas exchange impairment [forced expiratory volume i n 1 s (FEV1) = 79% pred; PaO2 = 87.4; alveolar-arterial oxygen tension gradient (AaPO(2)) = 22.9 mm Hg]. By analysing nitrogen washout curve s, an alveolar slow space representing 45.1% of total lung volume (vs. 36.8% in normals; p = 0.044) was identified; its alveolar ventilation per minute per unit lung volume ((V) over dot(A2)/L-2) was lower than in normals (p = 0.01). beta-Agonist inhalation by the asthmatics, whi ch reversed airway obstruction (FEV1 = 98% pred.; p < 0.001) and impro ved gas exchange (PaO2 = 92.6 mm Hg, p < 0.001; AaPO(2) = 16.8 mm Hg, p = 0.003), led to a highly significant increase in (V) over dot(A2)/L -2 (P = 0.001). The improvement in PaO2 was associated with the increa se in ir (V) over dot(A2)/L-2 (r(2) = 0.39; p = 0.017), but not with t he increase in FEV1. Lastly, the changes in FEV1 and (V) over dot(A2)/ L-2 were not correlated with each other. We conclude that even in mild stable asthma there is substantial unevenness of ventilation, detecta ble by bicompartmental analysis of nitrogen washout curves, which is r esponsible for gas exchange impairment and is not related to common sp irometric parameters. In addition, the improvement in gas exchange is probably due to the effect of fenoterol on the tributary airways of th e alveolar slow compartment. This effect can be assessed by this simpl e method, which can be used in clinical pharmacology studies and in th e follow-up of asthmatic patients.