Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.

BACKGROUND: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery. OBJECTIVES: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol. METHODS: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes). RESULTS: There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone. CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.

Evaluation of an abbreviated adenosine monophosphate bronchial challenge.

RATIONALE: Airway hyperresponsiveness to adenosine monophosphate (AMP) has been validated as a surrogate marker for airway inflammation. We wished to know whether an abbreviated challenge at the final threshold dose would produce the same fall in FEV1 as a full, conventional dose-response challenge. METHODS: Seventeen patients with mild-to-moderate asthma (mean FEV1, 75.5% predicted) attended for a full dose-response protocol, where the highest concentration of AMP to produce > 20% fall in FEV1 was noted, along with the maximum percentage fall and recovery time. Patients returned within 2 days for a further challenge, when they received only the highest concentration (as a single bolus) reached on the previous visit. RESULTS: The mean (+/- SEM) percentage fall in FEV1 after the full challenge was 25.5 +/- 1.3%, and after the abbreviated challenge was 9.4 +/- 2.4%. The mean recovery after the full challenge was 28.13 +/- 4.65 min, and after the abbreviated test was 10.81 +/- 4.27 min. CONCLUSION: An abbreviated challenge using a single bolus dose of AMP grossly underestimates bronchial hyperresponsiveness. Although the pharmacologic half-life of AMP is short (90 s), the lesser response and shortened recovery with the abbreviated challenge suggest a more prolonged physiologic half-life, which in turn may have implications for abbreviated challenge protocols.

Comparative cutoff points for adenosine monophosphate and methacholine challenge testing.

BACKGROUND: Current use of the PC20 (provocation concentration that causes a decrease in forced expiratory volume in 1 second of 20%) cutoff point for bronchial challenge precludes its use in patients with more severe airflow obstruction. OBJECTIVE: To evaluate the efficacy and safety of lower cutoff points for adenosine monophosphate (AMP) and methacholine (MCH) bronchial challenge tools to monitor response to treatment in chronic asthma. METHODS: We retrospectively examined data from 5 previously published studies (2 using AMP, 2 using MCH, and 1 with MCH and AMP arms) and recalculated 10% and 15% cutoff points for AMP and MCH. Data were analyzed for correlation of single results and doubling dose shifts after anti-inflammatory treatment intervention. RESULTS: A total of 175 individual MCH challenges and 152 AMP challenges were evaluated. Evaluating the doubling dose shift produced by the addition of anti-inflammatory treatment (inhaled corticosteroids or montelukast) produced the following Pearson correlation coefficients: MCH PD20 (provocation dose that causes a decrease in forced expiratory volume in 1 second of 20%) vs PD15, 0.80; MCH PD20 vs PD10, 0.65; AMP PC20 vs PC15, 0.96; and AMP PC20 vs PC10, 0.84 (P < .001 for all). Subgroup analysis of AMP for before and after inhaled corticosteroids only (n = 41) shows AMP PC20 vs PC15 of 0.92 and AMP PC20 vs PC10 of 0.84 (P < .001 for both). CONCLUSIONS: The 10% and 15% cutoff points strongly predict the 20% cutoff value for AMP and MCH, as do the doubling dose shifts after anti-inflammatory treatment. The lower thresholds are suitable for monitoring response to therapy, and they expose patients to significantly less provocation agent.