BackgroundAsthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations.Methodology/Principal FindingsOver the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations.Conclusions/SignificanceThis study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.

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Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.

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Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are suggested, as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.