Phosphodiesterase V inhibition reduces airway responsiveness, but does not improve the beneficial effect of deep inspiration
Abstract
Background: Deep inspirations (DIs) can prevent (bronchoprotection; BP) and reverse (bronchodilation; BD) methacholine (Mch)-induced bronchoconstriction, but this effect is reduced or absent in people with asthma or airways hyperresponsiveness (AHR). The mechanisms of this defect are unknown.
Objective: To indirectly examine the role of guanosine 3',5'-cyclic monophosphate (cGMP) by testing the hypothesis that the phosphodiesterase (PDE) V inhibitor, sildenafil, would improve DI-induced BP in individuals with AHR.
Methods: Thirty-two individuals were screened and 15 met all the inclusion/exclusion criteria (7 subjects with AHR and 8 healthy subjects). A single-dose Mch challenge inducing a 20% reduction in FEV1 in the absence of DIs was first identified. Thereafter, every study participant had 4 pairs of visits, each pair testing DI-induced BP and BD against the single-dose Mch, with no drug, or pretreatment with 25, 50 and 100 mg of sildenafil, respectively, in consecutive order.
Results: Sildenafil did not influence baseline lung function. However, in the absence of DIs, the drug caused a dose-dependent attenuation of the Mch-induced decrease in FEV1 by 17% (median value; 25th percentile: 1, 75th percentile: 16), 35% (-3, 61) and 37% (13, 79) for the 25-, 50- and 100-mg doses, respectively (p = 0.0004). No differences between the two participant groups were found. There were no effects of sildenafil on DI-induced BP or BD.
Conclusion: We infer from these results that the…
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Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 8 participants or records.
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