Efficacy of Inhaled Corticosteroids in Treatment of Exercise-Induced Bronchoconstriction in Adolescent Swimmers

Introduction: Exercise-induced bronchoconstriction (EIB) is a pulmonary disorder mostly associated with athletes that causes acute airway narrowing during exercise. The treatment of choice is a short-acting beta agonist such as albuterol to assist with airway dilation, but this treatment has been inefficient in athletes who are exposed to inhaled irritants such as swimmers. The swimming world fears that repetitive albuterol use can give athletes a boost due to its side effects. Therefore, this review examines the use of inhaled corticosteroids (I) for management of symptoms such as wheezing and shortness of breath (O) in adolescent swimmers diagnosed with EIB (P) compared to the treatment of choice (C). Methods: A literature search was performed in November 2018 which yielded six results consisting of two randomized control trials, two cross-sectional studies, a cohort study and a case-control study. Results were obtained from Google Scholar and PubMed, where their results and study design were compared and analyzed. Results: Five of the six studies revealed statistically significant improvement in Forced Expiratory Volume (FEV1) among subjects when given either a short-acting beta agonist (SABA) or an inhaled corticosteroid (ICS). Although the studies were not specific enough or necessarily directed at answering the objective question, each study gave an answer to a piece of the puzzle that determines a positive outcome for inhaled corticosteroid use in swimmers specifically. One study determined that mannitol challenge testing was the most sensitive and specific test for diagnosing EIB in swimmers. Two studies revealed that the athlete’s symptoms improved after ICS use and had long-term improvements in FEV1 after mannitol challenge testing. One study determined that basophils play a role in the pathophysiology of EIB determining that immune modulation therapy could be beneficial in EIB Discussion: Most of the studies found positive outcomes in their results, and this analysis uses multiple different types of studies. Variables in the analysis that were strong across the studies were statistical significance of results, lack of bias, and data analysis. Variables that needed improvement were sample size, age of subjects, blinding, and treatment timelines. Even though there is positive evidence from strong studies for the benefit of inhaled corticosteroids for swim athletes, the study topics themselves are not specific enough to the study question. Conclusion: Inhaled corticosteroids are already considered a long-term maintenance therapy of obstructive pulmonary conditions such as asthma, but this analysis was performed to determine the significance of this therapy for exercise-induced bronchoconstriction in swimmers specifically. After piecing the results of these articles together, it was determined that inhaled corticosteroids are a rather safe alternative for long-term management of EIB in swimmers

Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response

Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen