Rj. Dockhorn et al., PROVENTIL HFA PROVIDES PROTECTION FROM EXERCISE-INDUCED BRONCHOCONSTRICTION COMPARABLE TO PROVENTIL AND VENTOLIN, Annals of allergy, asthma, & immunology, 79(1), 1997, pp. 85-88
Introduction: During the 1970s, scientists suggested that the growing
use of chlorofluorocarbons (CFCs) was contributing to depletion of the
stratospheric ozone layer with potentially harmful results. A committ
ee on the ozone layer organized the preparation of the Montreal Protoc
ol. This protocol mandated the cessation of production and use of CFCs
by January 1, 1996. The primary exemption to this ban is for the use
of CFCs as propellants in metered dose inhalers (MDIs) for the treatme
nt of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants
, such as HFA-134a, for use in MDIs have been identified. Albuterol, a
selective beta-adrenergic agonist, currently widely available for inh
alation asthma therapy, has been reformulated in HFA-134a (Proventil H
FA). Objective: To compare the efficacy of Proventil HFA to Ventolin,
Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients
from exercise-induced bronchoconstriction. Methods: This was a random
ized, single-blind, placebo-controlled, 4-period crossover study of as
thmatic patients with documented exercise-induced bronchoconstriction.
Twenty patients self administered two puffs of either Proventil HFA,
Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to perfo
rming a standardized exercise challenge at the study site. Spirometry
was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes af
ter completion of the exercise challenge. Heart rate and blood pressur
e were measured just prior to spirometry and a 12-lead ECG was perform
ed 15 minutes after completion of the exercise challenge for measureme
nt of the QT corrected interval. Results: The primary efficacy variabl
e was the smallest percent change from the predose FEV1 following exer
cise. The smallest percent change from predose FEV1 for Proventil HFA
was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and t
he 3.6 +/- 10.2 SD for Proventil. The smallest percent change from pre
dose FEV1 for each of the active treatments was significantly differen
t from placebo, -23.7 +/- 14.5. Twelve of the patients had a greater t
han or equal to 20% fall in FEV1 post-exercise with placebo pretreatme
nt, but only 1, 1, and 0 had greater than or equal to 20% FEV1 falls a
fter treatment with Proventil HFA, Ventolin, and Proventil respectivel
y. Changes in heart rate, blood pressure and QT corrected interval wer
e similar for the three active treatments following exercise. Conclusi
ons: Proventil HFA provides protection against exercise-induced bronch
oconstriction comparable to Ventolin and Proventil and protection supe
rior to placebo. Proventil HFA has a safety profile similar to Ventoli
n when used to prevent exercise-induced bronchoconstriction.