Magnitude of bronchoprotection of albuterol vs methacholine: relationship to baseline airway caliber.

Airway hyperresponsiveness (AHR) to methacholine likely relates to smooth muscle dysfunction in asthma patients and to a geometric function of reduced airway caliber in COPD patients.1 This geometric phenomenon should contribute to AHR in asthmatic patients with nonreversible obstruction. Therapy with albuterol markedly protects against methacholine-induced smooth muscle contraction.2–5 We hypothesize that the geometric AHR component due to airway narrowing in asthma patients should be less inhibited by the administration of albuterol. In this brief report, we examine data from previous studies2–5 in 28 asthmatic patients. All patients were nonsmokers with no other lung disease. All had refrained from using inhaled 2-agonists for 2 weeks (indicating that 2-agonist tolerance would not affect the magnitude of bronchoprotection), and no patients were using controller medications. Study subjects were chosen only once, sequentially, as follows: 12 patients from one study2; 7 patients from a second study3; 6 patients from a third study4; and 3 patients from a fourth study.5 The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was measured before and 10 min after inhaling 2 puffs (200 g) of albuterol. The bronchoprotective effect of albuterol was expressed as the dose-shift,2–5 which is the number of doubling concentrations that the PC20 had improved after albuterol administration. We examined the baseline FEV1 in the 10% strata, with 3 patients between 70 and 79% predicted, 8 patients between 80 and 89% predicted, 10 patients between 90 and 99% predicted, and 7 patients at 100% predicted. There was a wide range of bronchoprotection (0.7 to 5.4 doubling doses; mean [ SD] number of doubling doses, 3.2 1.0). There was no overall significant relationship between baseline FEV1 and bronchoprotection; however, in the FEV1 stratified data, a trend emerged (Fig 1). The mean bronchoprotection increased from 2.3 doubling concentrations in subjects with an FEV1 in the 70% predicted range to 3.6 doubling concentrations for those with an FEV1 of 100% predicted. The regression of these four data points is significant (r 0.96; p 0.027). These data are not definitive. However, they do support the hypothesis that the AHR component due to airway obstruction is less inhibited by therapy with inhaled 2-agonists. Confirmation in one or more larger studies comparing this in asthma vs COPD patients would be particularly interesting.