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Exercise-induced bronchoconstriction (EIB) describes the condition whereby exercise causes airflow obstruction that lasts for up to 90 minutes without treatment. This double-blind, placebo-controlled, five-way crossover study investigated the dose response and duration of action of a 5-lipoxygenase-activating protein inhibitor, GSK2190915, to inhibit EIB in subjects with asthma. Forty-seven subjects with EIB were enrolled. Exercise challenge testing was scheduled at 2, 9.5, and 24 hours after receiving a single dose of GSK2190915 (10, 50, 100, and 200 mg) or placebo in randomized order. GSK2190915 at 200 and 100 mg significantly attenuated the response to exercise at 2 and 9.5 hours postdose, respectively, compared with placebo. The adjusted mean maximum percentage change from baseline forced expiratory volume at 1 second within 60 minutes postexercise challenge (FEV1 (0-60)) treatment difference for GSK2190915 at 200 mg compared with placebo at 2 hours postdose was 6.30% (95% CI, 3.06, 9.54), corresponding to a 40% attenuation of the placebo response to exercise; the treatment difference between GSK2190915 at 100 mg and placebo at 9.5 hours postdose was 3.49% (95% CI, 1.02, 5.95), corresponding to a 41% attenuation of the placebo response to exercise. No significant effect was seen at 24 hours postdose with any dose; however, investigation of statistically significant treatment-related effects at this time point was limited because of the small fall in adjusted mean FEV1 (0-60) (-7.61%; 95% CI, -10.23, -4.99) after placebo. GSK2190915 may be of benefit in EIB prevention. GSK Clinical Study LPA112025; ClinicalTrials.gov identifier number: NCT00812929. [ABSTRACT FROM AUTHOR]

Background: GSK2190915, a 5-lipoxygenase activating protein inhibitor, inhibits the production of cysteinyl leukotrienes and leukotriene B4 and 5-oxo-6,8,11,14-eicosatetraenoic acid. We have previously reported that GSK2190915 100 mg daily inhibits early and late asthmatic responses to inhaled allergen; the effects of lower doses have not been reported. This study assessed the dose-response effects of GSK2190915 10 mg and 50 mg on the early asthmatic response (EAR) to inhaled allergen. Methods: Nineteen subjects with mild asthma and an EAR were enrolled in a randomized, double-blind, three-way crossover study of GSK2190915 10 mg, 50 mg, and placebo orally once-daily for 3 days. Allergen challenge was performed 2 hours after the third dose. Results: Compared with placebo, GSK2190915 10 mg and 50 mg caused significant, dosedependent attenuation of the minimum forced expiratory volume at 1 second (FEV1) absolute change from baseline; mean treatment differences were 0.21 L (95% confidence interval [CI] 0.04 L, 0.38 L) and 0.41 L (95% CI 0.24 L, 0.58 L), respectively. GSK2190915 50 mg was more effective than 10 mg; mean difference between treatments was 0.20 L, (95% CI 0.03 L, 0.36 L). Compared with placebo, GSK2190915 50 mg, but not 10 mg, significantly inhibited the weighted mean FEV1 absolute change from baseline. Conclusion: GSK2190915 50 mg attenuated the EAR similarly to GSK2190915 100 mg in our previous study, suggesting 50 mg is at the top of the dose-response curve. GSK2190915 10 mg is a suboptimal dose. The EAR can be used to assess the therapeutic dose of a new treatment for asthma. [ABSTRACT FROM AUTHOR]

Understanding how health care system structures, processes, and available resources facilitate and/or hinder the delivery of quality cancer care is imperative, especially given the rapidly changing health care landscape. The emerging field of cancer care delivery research (CCDR) focuses on how organizational structures and processes, care delivery models, financing and reimbursement, health technologies, and health care provider and patient knowledge, attitudes, and behaviors influence cancer care quality, cost, and access and ultimately the health outcomes and well-being of patients and survivors. In this article, we describe attributes of CCDR, present examples of studies that illustrate those attributes, and discuss the potential impact of CCDR in addressing disparities in care. We conclude by emphasizing the need for collaborative research that links academic and community-based settings and serves simultaneously to accelerate the translation of CCDR results into practice. The National Cancer Institute recently launched its Community Oncology Research Program, which includes a focus on this area of research., (© 2015 by American Society of Clinical Oncology.)