Adding montelukast to fluticasone propionate/salmeterol for control of asthma and seasonal allergic rhinitis.

Limited information exists comparing fluticasone propionate/salmeterol combination (FSC) versus montelukast (MON) in patients with coexistent asthma and allergic rhinitis. The purpose of this study was to compare the addition of MON to patients receiving FSC on asthma control while experiencing asthma and allergy symptoms. Additionally, the effect of fluticasone propionate aqueous nasal spray (FPANS) and MON were assessed in allergic rhinitis control. Symptomatic patients (n = 1385) with asthma and seasonal allergic rhinitis were randomized to receive FSC, 100/50 micrograms twice daily; FSC twice daily + FPANS, 200 micrograms once daily; FSC twice daily + MON, 10 mg once daily; or MON once daily for 4 weeks during the allergy pollen season. Patients recorded peak expiratory flow, rescue albuterol use, and asthma and rhinitis symptoms. No additional improvements in overall asthma control were seen when MON was added to FSC. Treatment with FSC produced significant (p < 0.001) improvements in all clinical and patient-reported measures versus MON. FSC + FPANS was superior to FSC + MON (p < or = 0.001) in improving daytime and nighttime total nasal symptom scores. Adverse events were similar. In patients with asthma and allergic rhinitis, adding MON to FSC provided no additional benefit in asthma control. FSC resulted in superior improvement in asthma control compared with MON. FPANS also provided superior nasal symptom control versus MON in allergic patients treated with FSC for asthma. Optimal disease control in patients with asthma and allergic rhinitis should be achieved by the most effective therapy directed toward each disease component.

alpha(4)beta(1) Integrin activation of L-type calcium channels in vascular smooth muscle causes arteriole vasoconstriction.

A pathway for the regulation of vascular tone appears to involve coupling between integrins and extracellular matrix proteins or their fragments and the subsequent modulation of ion movement across the smooth muscle cell membrane. Here, we report that the activation of L-type voltage-activated Ca(2+) channels occurs through a novel interaction of alpha(4)beta(1) integrin with peptides containing the Leu-Asp-Val (LDV) integrin--binding sequence, which is found in the CS-1 region of an alternately spliced fibronectin variant. Experiments were conducted on arterioles isolated from rat skeletal muscle. Arterioles exhibited sustained concentration-dependent vasoconstriction to LDV peptides but not to Leu-Glu-Val (LEV) control peptides. The constriction was associated with increased smooth muscle cell [Ca(2+)](i), as measured by using fura 2. The response could be inhibited with a function-blocking anti--alpha(4) integrin antibody. Removal of the endothelium did not alter the vasoconstrictor response. Further experiments demonstrated that the vasoconstriction was abolished by the L-type Ca(2+) channel inhibitor nifedipine and the Src family kinase inhibitor PP2. In studies of isolated smooth muscle cells using whole-cell patch-clamp methods, the L-type current was enhanced by the LDV but not LEV peptide and was blocked by PP2 or antibodies to alpha(4) integrin. Collectively, these data indicate that activation of alpha(4)beta(1) integrin leads to enhanced influx of Ca(2+) through L-type channels by activating a tyrosine kinase pathway, leading to vasoconstriction. Involvement of integrins in the modulation of vascular tone may be particularly important in vascular responses to mechanical signals, such as pressure and flow, and to tissue injury after damage to the extracellular matrix.

Evaluation of fluticasone propionate and fluticasone propionate/salmeterol combination on exercise in pediatric and adolescent patients with asthma.

OBJECTIVE: This study was designed to demonstrate that four weeks of fluticasone propionate (FP) 100 micrograms (mcg) combined with salmeterol 50 mcg twice daily (BID) via DISKUS(®) resulted in protection against bronchospasm induced by activity, as measured by standardized exercise challenge testing in pediatric and adolescent subjects who required regular use of inhaled corticosteroids for the treatment of persistent asthma. METHODS: Prior to study entry, all patients reported regular use of inhaled corticosteroids (ICS). During screening all patients demonstrated ≥20% fall in FEV(1) following exercise. RESULTS: A total of 231 subjects aged 4 to 17 were randomized to the two study treatments: 113 to the FP/salmeterol combination group (FSC) and 118 to receive FP 100 mcg BID. Of the subjects randomized, 106 (94%) subjects in the FSC 100/50 group and 108 (92%) subjects in the FP 100 group completed the study. At the end of treatment (Week 4), both FSC and FP protected against a fall in FEV(1) following exercise in patients who at baseline experienced ≥20% fall in FEV(1) following exercise. A mean decrease in FEV(1) of 9.9% was observed in the FSC 100/50 group as compared with a mean decrease of 11.1% in the FP 100 group; there was no statistical difference between treatments. CONCLUSION: Both FSC 100/50 and FP 100 provided protection against an exercised-induced fall in FEV(1); but statistically significant differences we not noted. Both treatments were well-tolerated over four weeks and FSC 100/50 had an adverse event profile comparable to that observed with FP 100.