Mariana Couto

A systematic review of statin efficacy in asthma.

Background. Statins are known for their lipid-lowering effects and role in the treatment of atherosclerotic disease. They also have anti-inflammatory and immunomodulatory properties which could benefit asthma patients. We aimed to review the evidence on the efficacy and safety of statins in asthma-related outcomes. Methods. A systematic review of the literature on the effects of statins on asthma-related outcomes was performed following a search of the National Guideline Clearinghouse, Cochrane, Scopus, and Pubmed Medline databases in January 2012. Randomized controlled trials (RCTs) and observational studies (cohort/case–control design) assessing the effect of statins were included. The Grading of Recommendations Assessment Development and Evaluation (GRADE) system was used to rate the levels of evidence and grade of recommendation. Results. Twenty-four of the 379 articles retrieved electronically and one article identified by hand search were selected for full-text scrutiny by two independent reviewers. Eight studies were included: six RCTs and two observational studies. Statin use was not associated with consistent, statistical significant improvements in patient outcomes (asthma control, quality of life, steroid-sparing effects) or disease outcomes (lung function, airway responsiveness), and all the studies analyzed had low or very low quality of evidence. Inflammatory outcome improvements were observed in mild allergic asthma. Conclusion. Statins do not seem to have any additional benefit in asthma control or steroid-sparing effect in asthma treatment. Considering the prevalence of both statin use and asthma, more, better designed studies are needed to determine whether a specific phenotype of asthma exists that could benefit from statin treatment.

Two distinct phenotypes of asthma in elite athletes identified by latent class analysis

Abstract Introduction: Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. Methods: In the present cross-sectional study, an analysis of athletes’ records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. Results: Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: “atopic asthma” defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and “sports asthma”, defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype “sports asthma” was significantly increased in athletes practicing water (OR = 2.87; 95%CI [1.82–4.51]) and winter (OR = 8.65; 95%CI [2.67–28.03]) sports, when compared with other athletes. Conclusion: Two asthma phenotypes were identified in elite athletes: “atopic asthma” and “sports asthma”. The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of “sports asthma”. Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments.

Exploratory study comparing dysautonomia between asthmatic and non-asthmatic elite swimmers.

BACKGROUND Dysautonomia has been independently associated with training and exercise-induced bronchoconstriction. In addition, neurogenic airway inflammation was recently associated with swimmers-asthma. We aimed to assess the relation between autonomic nervous system and airway responsiveness of asthmatic elite swimmers. METHODS Twenty-seven elite swimmers, 11 of whom had asthma, were enrolled in this exploratory cross-sectional study. All performed spirometry with bronchodilation, skin prick tests and methacholine challenge according to the guidelines. Pupillometry was performed using PLR-200™ Pupillometer. One pupil light response curve for each eye was recorded and the mean values of pupils maximal and minimal diameters, percentage of constriction, average and maximum constriction velocities (parasympathetic parameters), dilation velocity, and total time to recover 75% of the initial size (sympathetic parameters) were used for analysis. Asthma was defined using IOC-MC criteria; subjects were divided into airway hyperesponsiveness (AHR) severity according to methacholine PD20 in: no AHR, borderline, mild, moderate and severe AHR. Differences for pupillary parameters between groups and after categorization by AHR severity were assessed using SPSS 20.0 (p ≤ 0.05). In individuals with clinically relevant AHR, correlation between PD20 and pupillary parameters was investigated with Spearmans correlation test. RESULTS No statistically significant differences were observed between asthmatic and non-asthmatic swimmers regarding parasympathetic parameters. When stratified by AHR, maximal and minimal diameters and percentage of constriction were significantly lower among those with severe AHR. Among swimmers with clinically relevant AHR (n = 18), PD20 correlated with parasympathetic activity: maximal (r = 0.67, p = 0.002) and minimal diameters (r = 0.75, p<0.001), percentage of constriction (r = -0.59, p = 0.011) and latency (r = 0.490, p = 0.039). CONCLUSIONS No significant differences were observed between asthmatic and non-asthmatic swimmers regarding parasympathetic parameters, but among those with relevant AHR an association was found. Although limited by the sample size, these findings support the relation between dysautonomia and AHR in asthmatic swimmers.

Exhaled breath temperature in elite swimmers: The effects of a training session in adolescents with or without asthma

Cooling of the airways and inflammation have been pointed as possible mechanisms for exercise‐induced asthma (EIA). We aimed to investigate the effect of training and asthma on exhaled breath temperature (EBT) of elite swimmers.

Increased bronchial parasympathetic tone in elite cross-country and biathlon skiers: a randomised crossover study

This article has been retracted.

Exequibilidade do estudo funcional respiratório em idade pré-escolar na prática clínica

INTRODUCTION The assessment of respiratory function in preschool children, which has recently been attracting considerable interest, has several methodological particularities. Whether this is feasible in clinical practice with large groups of patients still needs to be investigated. AIM To assess the feasibility of pulmonary function testing in preschool children in clinical practice, and report the degree of success achieved according to age. METHODS Retrospective analysis of lung function tests performed in children from 2 to 6 years old at the respiratory function laboratory of CUF Descobertas Hospital between September 2006 and August 2011. Whole-body pletismography without occlusion for specific airway resistance (sRaw) assessment and animated spirometry were performed using the equipment Jaeger 4.65 (Viasys Healthcare), before and after 400 μg of inhaled salbutamol via a spacer device. The research fulfilled international criteria (ATS/ERS) for acceptability and reproducibility. RESULTS Of 1,239 lung function tests performed, 1,092 (88%) had acceptable and reproducible criteria for spirometry (children with a mean age of 4.3±0.91 years; 60.7% male), and 979 (79%) for sRaw measurement. We were able to report FEV(1) in 801 (65%) tests (children with a mean age of 4.5±0.89 years). In 23 (2%) tests it was only possible to report FEV(0.5) (children with a mean age of 3.5±0.67 years) and in 268 (22%) only FEV(0.75) (children with a mean age of 4.0±0.89 years). CONCLUSION Spirometry and sRaw assessment in preschool children can be used in clinical practice, with an increasing success rate as children get older. Reporting maneuvers of 0.5 or 0.75 seconds facilitates spirometric evaluation in a larger number of children.

Mechanisms of exercise-induced bronchoconstriction in athletes: current perspectives and future challenges

The evidence of exercise‐induced bronchoconstriction (EIB) without asthma (EIBwA) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms is of major importance as EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby, we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads toward better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.

Effect of competitive swimming on airway inflammation: A 3-yr longitudinal study

To the Editor, In recent years, the observation that regular pool attendance, especially by young children, was associated with lung hyperpermeability and increased risk of developing asthma led to the ‘pool chlorine hypothesis’ (1). Accordingly, the increasing and largely uncontrolled exposure of young children to chlorination byproducts contaminating the air of indoor swimming pools could contribute to the childhood asthma rise in industrialized countries (1). Moreover, an increasing body of literature suggests an association between competitive swimming and asthma (2). A higher prevalence of asthma and asthma-like symptoms has been identified in elite swimmers. Environmental exposures, mechanical stress to the airways, increased prevalence of respiratory infections and dysautonomia, have been recognized as asthma contributory factors (2). Increased numbers of both eosinophils and mast cells were observed in bronchial biopsies of competitive adult swimmers, leading to believe that airway inflammation and hyper-responsiveness develop during the training career (3). While the latter seems to be a transient phenomenon (4), whether airway inflammation persists is still debated (5–7). Therefore, we aimed to assess changes in airway inflammation of swimmers during a 3-yr follow-up. Competitive non-elite young swimmers from the two main Portuguese swimming teams were invited (n = 120) to participate in this cohort prospective study. Informed consent was obtained from 105, which were assessed at the baseline visit. From these, 86 attended the 3-yr follow-up visit and were included in the final analysis. No significant differences were observed between the 19 lost to follow-up subjects and the remaining (Table 1). ‘Active swimmers’ were defined as those remaining at high level of competitive swimming; those who quitted at least 6 months before the follow-up visit were considered ‘past swimmers’. None of the subjects smoked. The local hospital ethical committee approved the study. Subjects completed a self-administered questionnaire, including questions from the ISAAC questionnaire, reporting physician diagnosis of asthma and allergic rhinitis, and use of asthma medication. Physical activity (PA) was measured using the short 7 days International Physical Activity Questionnaire (IPAQ) (8). A combined total physical activity was computed as the sum of the activity domains scores (total PA = walking + moderate-intensity PA + vigorous-intensity PA) and reported as a continuous measure (total PA score = total MET-min/wk). Eosinophilic airway inflammation was assessed measuring lower airway’s exhaled nitric oxide (NO) levels according to guidelines, before a training session, using NIOX MINO (Aerocrine AB, Solna, Sweden), and expressed in parts per billion (p.p.b.). Atopy was defined by positive skin prick testing to common aeroallergens (Laboratorios LETI S.L., Spain). The study was performed at the swimming pool in which swimmers trained, except for the follow-up visit of past swimmers which occurred at the laboratory. Results were expressed as mean (SD) or, if not normally distributed, as median (interquartile range). Levels of exhaled NO and of physical activity were log-transformed because of skewed distribution. Differences between groups were assessed with one-way ANOVA or Kruskal–Wallis for normally or nonnormally distributed data or chi-Square for categorical variables. Differences in changes in exhaled NO after the 3-yr follow-up were assessed by general linear model adjusting on confounding factors: gender, age, atopy, physician-diagnosed asthma, and use of asthma medication. We observed a significant difference in changes in exhaled NO; those who remained active significantly increased their levels of eosinophilic airway inflammation independently of their gender, age, atopy, or asthma status (Table 2, Fig. 1). After the 3-yr follow-up, the prevalence of asthma, allergic rhinitis, and use of asthma medication increased significantly in both groups. All subjects increased their overall physical activity levels; however, significant increases in moderate and vigorous physical activity level were only observed in active swimmers.

Impact of changes in anti-doping regulations (WADA Guidelines) on asthma care in athletes.

Objective:To investigate how changes to the World Anti-Doping Agency (WADA) guidelines on asthma medication requests have impacted the management of asthmatic athletes in Portugal. Design:Retrospective analysis of asthma medication requests submitted in 2008 to 2010. Setting:Portuguese Anti-Doping Authority database. Participants:Athletes requesting the use of inhaled corticosteroids and/or &bgr;2-agonists. Independent Variables:Demographic, therapeutic, and diagnostic test data. Main Outcome Measures:Yearly changes in number of asthma medication requests and diagnostic procedures. Results:We analyzed 326 requests: 173 abbreviated Therapeutic Use Exemptions (TUEs) in 2008 (objective tests not required), 9 Declaration of Use (DoU) and 76 TUEs in 2009, and 39 DoU and 29 TUEs in 2010. Spirometry was performed in 87% and 37% of athletes in 2009 and 2010, respectively; the corresponding figures for bronchoprovocation were 59% and 16%, almost all positive in both years. Conclusions:Applications for inhaler use have decreased by approximately half since objective asthma testing became mandatory. Our findings show that WADA guidelines have an impact on asthmatic athletes care: In 2009 a more rigorous screening was possible, leading to withdrawal of unnecessary medication. Constant changes, however, jeopardize this achievement and nowadays introduce safety issues stemming from the unsupervised use of inhaled &bgr;2-agonists.

Oxidative stress in asthmatic and non-asthmatic adolescent swimmers—A breathomics approach

We hypothesize that oxidative stress induced by trichloramine exposure during swimming could be related to etiopathogenesis of asthma among elite swimmers.