Impact of climate variability on exercise-induced bronchospasm in adolescents living in a semi-arid region / Influência de alterações climáticas sobre a ocorrência do broncoespasmo induzido por exercício em adolescentes de uma região semiárida

ABSTRACT Objective: To examine the impact of climate variability on the occurrence of exercise-induced bronchospasm in the rainy and dry seasons of a Brazilian semi-arid region. Methods: This sample comprised 82 adolescents aged 15 to 18 years, who were submitted to exercise-induced bronchospasm assessment on a treadmill and outdoors, during the rainy and the dry season. Anthropometric variables, sexual maturity and forced expiratory volume in the first second were analyzed. Air temperature and humidity, decline in forced expiratory volume in the first second (%) and frequency of bronchospasm were compared between seasons using the independent Student's t test, the Wilcoxon and McNemar tests, respectively. The level of significance was set at p<0.05. Results: The mean age was 15.65±0.82 years. Air temperature, air humidity and decline in forced expiratory volume in the first second (%) differed between seasons, with higher air temperature and humidity in the rainy season (29.6ºC±0.1 and 70.8%±0.6 versus 28.5ºC±0.2 and 48.5%±0.6; p<0.05). The decline in forced expiratory volume in the first second (%) was greater in the dry season (9.43%±9.97 versus 12.94%±15.65; p<0.05). The frequency of bronchospasm did not differ between seasons. Conclusion: The dry season had a negative impact on forced expiratory volume in the first second in adolescents, with greater decrease detected during this period. Findings of this study suggested bronchospasm tends to be more severe under low humidity conditions.

RESUMO Objetivo: Verificar a influência das alterações climáticas sobre o broncoespasmo induzido por exercício, nos períodos chuvoso e seco de uma região do semiárido brasileiro. Métodos: Foram submetidos à avaliação do broncoespasmo em esteira ergométrica, em ambiente externo, nos períodos chuvoso e seco, 82 adolescentes, com idades de 15 a 18 anos. Foram avaliadas as variáveis antropométricas, a maturação sexual e o volume expiratório forçado no primeiro segundo. Para comparação da temperatura e umidade, queda do volume expiratório forçado no primeiro segundo (%) e frequência do broncoespasmo entre os períodos, foram utilizados o teste t de Student independente, o teste de Wilcoxon e o teste de McNemar, respectivamente. O nível de significância adotado foi p<0,05. Resultados: A média de idade foi 15,65±0,82 anos. A temperatura, a umidade e a queda do volume expiratório forçado no primeiro segundo (%) diferiram entre os períodos, com valores de temperatura e umidade maiores no período chuvoso (29,6ºC±0,1 e 70,8%±0,6 versus 28,5ºC±0,2 e 48,4%±0,6; p<0,05). A queda do volume expiratório forçado no primeiro segundo (%) foi maior no período seco (9,43%±9,97 versus 12,94%±15,65; p<0,05), e não foi encontrada diferença da frequência do broncoespasmo entre os períodos. Conclusão: O período seco influenciou negativamente no volume expiratório forçado no primeiro segundo de adolescentes, observando maior percentual de queda dessa variável nesse período. De acordo com os achados, propõe-se uma maior gravidade do broncoespasmo induzido por exercício em condições de baixa umidade.

Los efectos del entrenamiento físico en niños asmáticos / Effects of exercise training in children with asthma

Asthma is a chronic obstructive respiratory disease with high prevalence in children. Several factors may trigger asthma symptoms, including exercise, which can lead to exercise-induced bronchoconstriction (EIB). Although physical exercise may represent a risk factor for triggering bronchial obstruction in asthmatics, studies have also indicated several positive effects. Thus, this article aimed to summarize current evidence on the effects of exercise training in children with asthma. There is substantial available evidence on the topic. Most of the findings show that exercise induce positive effects, including the increase of aerobic fitness, decrease of EIB levels, as well as an increase in both disease control and quality of life levels in asthmatic children. As for possible influencing factors in order to obtain exercise-induced positive effects, an adequate prescription of exercise intensity highlights and should be personalized, as well as established close to the anaerobic threshold. Thus, considering the evidence showing beneficial effects and the fact that the practice of physical exercise consists of a low cost and safe non-pharmacological therapy, supervised, personalized and individual recommendation of exercise training by health professionals are indicated to asthmatic children.

El asma es una enfermedad respiratoria obstructiva crónica con alta prevalencia en niños. Varios factores pueden desencadenar síntomas de asma, incluido el ejercicio, que puede conducir a la broncoconstricción inducida por el ejercicio (BIE). Aunque el ejercicio físico puede representar un factor de riesgo para desencadenar la obstrucción bronquial en los asmáticos, estudios también han indicado varios efectos positivos. Este artículo tiene como objetivo resumir la evidencia actual sobre los efectos del entrenamiento físico en niños con asma. Hay evidencia sustancial disponible sobre el tema. La mayoría de los hallazgos muestran que el ejercicio induce efectos positivos, incluido el aumento de la aptitud aeróbica, la disminución de los niveles de la BEI, así como un aumento tanto en el control de la enfermedad como en los niveles de calidad de vida en niños asmáticos. Se destaca la importancia de una prescripción de la intensidad del ejercicio adecuada y personalizada, cerca del umbral anaeróbico, para obtener los efectos positivos inducidos por el ejercicio. Por lo tanto, considerando la evidencia que muestra efectos beneficiosos y el hecho de que la práctica del ejercicio físico consiste en una terapia no farmacológica, segura y de bajo costo, el entrenamiento físico supervisado, personalizado e individualizado por parte de profesionales de la salud es recomendado para niños asmáticos.

Exercise-Induced bronchoconstriction and therapeutic modulation in Iraqi Girls Intermediate School Students

EIB (Exercise-Induced Bronchoconstriction) describes the narrowing that accurs in the airway follow a short period of exercise. EIB is found in 8-10% of normal children population as occult bronchospasm during or after physical activities. The mecanisms of EIB are related to rapid ventilation and mouth brathing which cause beat and water loss during breathing leading to bronchoconstriction. Peak Expiratory Flow Rate (PEFR) measured pre and post-exercise in students aged 12-16 years in girl intrmediate school. Any female shows PEFR values reduction 15% after 6 minutes continuous free running considered as asthmatic patient, this give an incidence rate of asthmatic patient of 9% in female students in this age. Treatment of EIB, Zafirlukast treatment gives (85.7%) protection rate. While salbutamol inhalation gives a protection rate 88%. Only 66.6% of girls with EIB give an improvement in PEFR values after sodium cromoglycate treatment. A regular measurement of PEFR in school students appears to be a good indicator of EIB, while inhalation of salbutaol 15 minutes before exercise give a good protection against EIB attacks at least for 4 hours (AU)

Asma inducida por ejercicio / Exercise­induced asthma

El asma es una enfermedad crónica que se caracteriza por la presencia de inflamación de las vías aéreas, que puede ser reversible. El ejercicio físico puede ser uno de los factores que pueden desencadenar síntomas en pacientes con o sin diagnóstico de asma bronquial. Actualmente hay dos hipótesis (térmica y osmótica) que justifican la causa del asma inducida por ejercicio (AIE). El diagnóstico de AIE se establece por cambios en la función pulmonar provocados por el ejercicio, y no en función de los síntomas. Existen diversas medidas farmacológicas y no farmacológicas destinadas al tratamiento de AIE. El entrenamiento físico es beneficioso tanto en niños como en adultos con asma. (AU)

Efecto agudo del ejercicio físico de intensidad moderada sobre las variables espirométricas en sujetos asmáticos broncodilatados. Prueba piloto / Acute effect of moderate-intensity exercise on spirometric variables in broncodilated asthmatic subjects. A pilot study

RESUMEN Introducción: el broncoespasmo inducido por el ejercicio (BIE) ocurre entre el 70 y 80 % de los asmáticos y su aparición es más frecuente al terminar una sesión de ejercicio físico, principalmente de intensidad vigorosa. Objetivo: evaluar el efecto agudo que puede tener el ejercicio físico de intensidad moderada sobre las variables espirométricas en sujetos asmáticos broncodilatados. Metodología: se realizó un estudio cuasi-experimental de tipo antes y después. Se incluyeron diez sujetos (edad promedio = 23 ± 4 años), los cuales fueron divididos en dos grupos: cinco sujetos asmáticos y cinco sanos. Los dos grupos realizaron 10 minutos de calentamiento, 20 minutos de ejercicio en banda sin fin al 60 % de la frecuencia cardíaca de entrenamiento, seguido de 5 minutos de recuperación. La función pulmonar fue evaluada antes del ejercicio y 15 minutos después del ejercicio. Resultados: se encontraron diferencias estadísticamente significativas entre grupos (con asma 6 % vs. sin asma -1 %, p = 0,03) en los cambios pre y pos del ejercicio de la relación del volumen espiratorio forzado en el primer segundo (VEF1) sobre la capacidad vital forzada (CVF). El análisis multivariado mostró que la CVF post ejercicio en el grupo con asma fue significativamente menor que el del grupo sin asma, ajustado por evaluación basal y masa corporal total. Conclusión: el ejercicio de intensidad moderada en banda sin fin, no mostró diferencias clínicamente significativas sobre los cambios del pre y post ejercicio de las variables espirométricas estudiadas, puesto que estos cambios en VEF1 o CVF no superaron el 10 % teniendo como referencia la evaluación basal.

SUMMARY Background: Exercise-Induced Bronchospasm (BIE) occurs in 70 % to 80 % of asthmatics and its occurrence is more frequent at the end of a session of physical exercise, mainly of vigorous intensity. Objective: To evaluate the acute effect of moderateintensity physical exercise on spirometric variables in asthmatic subjects. Methodology: A before-and-after type quasi-experimental design. Ten subjects were included (mean age= 23 ± 4 years), which were divided into two groups: five asthmatic subjects and five healthy subjects. Both groups performed 10 min of warm-up, 20 min of treadmill exercise at an intensity of 60 % of the Heart Rate Reserve, and a final cool-down of 5 minutes. Lung function was assessed before and 15 minutes after exercise. Results: There were statistically significant differences between groups (with asthma = 6 % vs. without asthma = -1 %, p = 0.03) in the pre-post-exercise changes of the ratio of the forced expiratory volume in one second and the forced vital capacity (FEV1/FVC). The multivariate analysis showed that post-exercise FVC in subjects with asthma was significantly lower than in subjects without asthma, after adjusting for the baseline assessment and total body mass. Conclusion: Moderate-intensity exercise on a treadmill did not shows clinically significant differences on the changes pre-post exercise of the studied spirometric variables, since the changes on FEV1 or FVC did not exceed 10 % having as reference the baseline evaluation.

Evaluación de la disnea asociada al ejercicio / Exercise-induced dyspnea evaluation

Exercise-induced dyspnea is a common pediatric question but difficult to address since usually symptoms are described ambiguously by the child or parents. Most of times dyspnea is secondary to poor training but sometimes may be due to an underlying condition like exercise-induced bronchoconstriction or vocal cord dysfunction. To provide clinicians with a practical approach about exercise-induced dyspnea we have review pathogenesis and clinical characteristics of respiratory diseases and proposed an algorithm for study.

Frecuentemente nos vemos enfrentados a evaluar un niño con síntomas vagos asociados al ejercicio que el mismo paciente o sus padres describen como ahogo o sensación de pecho apretado. La mayoría de las veces se trata de cansancio atribuible al ejercicio normal que solo refleja pobre condicionamiento físico del individuo; sin embargo, este cansancio puede ser desproporcionado al esfuerzo, lo que obliga a considerar enfermedades comunes como asma o poco comunes como disfunción de cuerdas vocales. El objetivo de esta revisión es actualizar el conocimiento aquellas enfermedades respiratorias que forman parte del diagnóstico diferencial de la disnea asociada al ejercicio y proponer un algoritmo de estudio que permita un acercamiento práctico según causas de origen.

Respiratory Function and Symptoms Post Cold Air Exercise in Female High and Low Ventilation Sport Athletes

PURPOSE: Cold weather exercise is common in many regions of the world; however, it is unclear whether respiratory function and symptom worsen progressively with colder air temperatures. Furthermore, it is unclear whether high-ventilation sport background exacerbates dysfunction and symptoms. METHODS: Seventeen active females (measure of the maximum volume of oxygen [VO(2max)]: 49.6±6.6 mL·kg⁻¹·min⁻¹) completed on different days in random order 5 blinded running trials at 0℃, -5℃, -10℃, -15℃, and -20℃ (humidity 40%) in an environmental chamber. Distance, heart rate, and rating of perceived exertion (RPE) were measured within each trial; forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%-75% (FEF₂₅₋₇₅), and forced expiratory flow at 50% (FEF₅₀) were measured pre- and post-test (3, 6, 10, 15, and 20 minutes). Respiratory symptoms and global effort were measured post-test spirometry. RESULTS: Mean decreases were found in FEV1 (4%-5% at 0℃, -5℃, -10℃, and -15℃; 7% at -20℃). FEF₂₅₋₇₅ and FEF₅₀ decreased 7% and 11% at -15℃ and -20℃, respectively. Post-exertion spirometry results were decreased most at 3 to 6 minutes, recovering back to baseline at 20 minutes. Respiratory symptoms and global effort significantly increased at -15℃ and -20℃ with decreased heart rate. High-ventilation sports decreased function more than low-ventilation participants but had fewer symptoms. CONCLUSIONS: These results indicate that intense exercise at cold air temperatures up to -20℃ is achievable; however, greater effort along with transient acute bronchoconstriction and symptoms of cough after exercising in temperatures colder than -15℃ are likely. It is recommended that individuals cover their mouth and reduce exercise intensity to ameliorate the effects of cold weather exercise.

Avaliação dos fatores de risco associados ao broncoespasmo induzido pelo exercício em crianças e adolescentes sem diagnóstico prévio de asma / Assessment of risk factors associated with exercise-induced bronchospasm in children and adolescents without prior diagnosis of asthma

Objetivo: Avaliar os fatores de risco associados ao broncoespasmo induzido pelo exercício (BIE) em crianças e adolescentes sem diagnóstico prévio de asma por meio dos parâmetros espirométricos. Métodos: 90 voluntários acima do percentil 85th do peso (EP) e 30 eutróficos (EU) participaram deste estudo. Foi realizado teste de broncoprovocação de acordo com o protocolo de Del Rio-Navarro et al. (2000), utilizando-se esteira ergométrica. O BIE foi considerado positivo quando o voluntário apresentou redução ≥ 10% do volume expiratório forçado no primeiro segundo (VEF1) basal, ou redução ≥ 26% do fluxo expiratório forçado entre 25 e 75% da capacidade vital forçada (FEF25-75%). Resultados: Houve associação do excesso de massa corpórea com o BIE demonstrado nas crianças e adolescentes, o que não foi observado com o nível de atividade física. Além disso, o diagnóstico positivo de BIE apresentou reduções significativas da função pulmonar até uma hora pós-exercício avaliado pelos métodos VEF1 e FEF25-75% da espirometria. Conclusão: O excesso de massa corporal pode influenciar no aumento da frequência de BIE em crianças e adolescentes sem o diagnóstico prévio de asma quando comparado a eutróficos por diferentes parâmetros na espirometria.

Objective: To assess risk factors associated with exercise-induced bronchospasm (EIB) in children and adolescents without prior diagnosis of asthma using spirometric parameters. Methods: 90 volunteers above the 85th percentile for weight (overweight) and 30 eutrophic participants were included in this study. EIB testing was performed according to the protocol proposed in 2000 by Del Rio-Navarro et al., using a treadmill. The EIB test was considered positive when there was a decrease of 10% or more in forced expiratory volume in one second (FEV1) or a reduction of 26% or more in forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75%). Results: There was an association between EIB and excess body mass in children and adolescents, but not between EIB and level of physical activity. Furthermore, the diagnosis of EIB was associated with prolonged significant reductions in pulmonary function parameters FEV1 and FEF 25­75%.Conclusion: Excess body weight may increase the frequency of BIE in children and adolescents without prior diagnosis of asthma when compared with eutrophic subjects, based on different spirometric parameters.

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA). RESULTS: The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other. CONCLUSIONS: Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.

Is Performance of a Modified Eucapnic Voluntary Hyperpnea Test in High Ventilation Athletes Reproducible?

PURPOSE: Exercise-induced bronchoconstriction (EIB) is common in “high ventilation” athletes, and the Eucapnic Voluntary Hyperpnea (EVH) airway provocation test is the standard EIB screen. Although the EVH test is widely used, the in-test performance in high ventilation athletes as well as the reproducibility of that performance has not been determined. Reproducibility of pre- and post-test spirometry and self-reported atopy/cough was also examined. METHODS: High ventilation athletes (competitive swimmers; n=11, 5 males) completed an atopy/cough questionnaire and EVH testing (operator controlled FiCO₂) on 2 consecutive days. RESULTS: Swimmers achieved 85%±9% and 87%±9% of target FEV1 volume on days 1 and 2, respectively, (P=0.45; ICC 0.57 [0.00-0.86]) resulting in a total ventilation of 687 vs 684 L [P=0.89, ICC 0.89 (0.65-0.97]) equating to 83%±8% and 84%±9% of predicted total volume (ICC 0.54 [0.00-0.85]) between days 1 and 2. FiCO₂ required to maintain eucapnic conditions was 2.5%. Pre-test FEV1 was less on day 2 (P=0.04; ICC >0.90). Day 1 to 2 post-test FEV1 was not different, and 4 swimmers were EIB positive (>10% fall in pre-post FEV1) on day 1 (3 on day 2). CONCLUSIONS: EVH in-test performance is reproducible however required less FiCO₂ than standard protocol and the swimmers under-ventilated by 125 and 139 L/min for days 1 and 2, respectively. How this affects EIB diagnosis remains to be determined; however, our results indicate a post-test FEV1 fall of ≥20% may be recommended as the most consistent diagnostic criterion.

Overweight effect on spirometric parameters in adolescents undergoing exercise / Efeito do excesso de peso sobre parâmetros espirométricos de adolescentes submetidos ao exercício

ABSTRACT Objective To evaluate effects of overweight on spirometric parameters in adolescents who underwent bronchial provocation test for exercise. Methods We included 71 male adolescents. The diagnosis of asthma was done based on participants’ clinical history and on the International Study Questionnaire Asthma and Allergies in Childhood, and the diagnosis of obesity was based on body mass index above 95th percentile. The bronchospasm induced by exercise was assessed using the run-walk test on a treadmill for eight minutes. The decrease in forced expiratory volume in one second > or equal to 10% before exercise was considered positive, and to calculate the intensity in exercise-induced bronchospasm we measured the maximum percentage of forced expiratory volume in one second and above the curve area. Data analysis was carried out using the Mann-Whitney U test and Friedman test (ANOVA), followed by Wilcoxon test (p<0.05). In addition, we used Fisher’s exact test to analyze the exercise-induced bronchospasm frequency. Results Significant differences were observed among obese adolescents in exercise-induced bronchospasm frequency (p=0,013) and in relation to time required for recovery after exercise (p=0,007). Conclusion Overweight can influence the increase in the exercise-induced bronchospasm frequency in non-asthmatic adolescents compared with eutrophic adolescents.

RESUMO Objetivo Avaliar o efeito do excesso de peso sobre parâmetros espirométricos em adolescentes submetidos ao teste de broncoprovocação por exercício. Métodos Participaram do estudo 71 adolescentes do sexo masculino. O diagnóstico de asma foi obtido por meio de histórico clínico e do questionário International Study of Asthma and Allergies in Childhood, e o de obesidade, pelo índice de massa corporal acima do percentil 95. Para avaliar o broncoespasmo induzido pelo exercício, utilizou-se o teste correr/caminhar em esteira ergométrica, com duração de 8 minutos, considerando positivo se diminuição do volume expiratório forçado no primeiro segundo >10% do valor pré-exercício e, para a intensidade do broncoespasmo induzido pelo exercício, foram utilizados o cálculo da queda percentual máxima do volume expiratório forçado no primeiro segundo e a área acima da curva. A análise dos dados foi realizada pelo teste U Mann-Whitney e pela ANOVA de Friedman, seguido do teste de Wilcoxon (p<0,05). O teste de Fisher foi empregado para analisar a frequência de broncoespasmo induzido pelo exercício. Resultados Foram encontradas diferenças significativas quanto à frequência de broncoespasmo induzido pelo exercício (p=0,013) e ao tempo de recuperação pós-exercício (p=0,007) nos adolescentes obesos. Conclusão O excesso de peso pode influenciar no aumento da frequência de broncoespasmo induzido pelo exercício em adolescentes não asmáticos, quando comparados a eutróficos.

Influence of polymorphisms of the beta-2 adrenergic receptor on the presence of exercise-induced bronchospasm in adolescents / Influência dos polimorfismos no receptor beta 2 adrenérgico na presença de broncoespasmo induzido pelo exercício em adolescentes

To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2) in triggering exercise-induced bronchospasm (EIB) in adolescents. Methods: The subjects were divided into two groups: present EIB (EIB+) (n=45) and absent EIB (EIB−) (n=115). The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1). The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann–Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. Results: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB− (p<0.05). There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB− groups (p=0.26; p=0.97 and p=0.43, respectively). However, there was a trend toward statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB− group (p=0.08). Conclusions: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend toward greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents.

Determinar a influência dos polimorfismos dos receptores adrenérgicos beta 2 (ADRB2) no desencadeamento de broncoespasmo induzido pelo exercício (BIE) em adolescentes. Métodos: Os sujeitos foram divididos em dois grupos: BIE presente (BIE+) (n=45) e BIE ausente (BIE−) (n=115). O teste de broncoprovocação com exercício foi feito com protocolo que consistiu em caminhar/correr durante no mínimo oito minutos em intensidade superior a 85% da frequência cardíaca máxima, considerando como BIE presente uma queda de 10% do volume expiratório forçado no primeiro segundo (VEF1). A genotipagem do gene ADRB2 foi feita pelo método Taqman por meio do aparelho Step One Plus. Para análise estatística usaram-se os testes t independente, U de Mann-Whitney, qui-quadrado e coeficiente de correlação de Spearman. Resultados: Idade, massa corporal, estatura, VEF1, CVF e relação VEF1/CVF foram menores no grupo BIE+ em comparação com o BIE− (p<0,05). Não houve diferenças significativas na proporção do alelo na posição 27 e dos genótipos Arg16Gly e Gln27Glu entre os grupos BIE+ e BIE− (p=0,26; p=0,97 e p=0,43, respectivamente). Entretanto, verificou-se uma tendência à significância estatística na maior proporção do alelo Gly16 para o grupo BIE+ comparado com o BIE− (p=0,08). Conclusões: A presença de polimorfismos associados ao alelo Glu27 e os genótipos Arg16Gly e Gln27Glu não influenciam no BIE. Porém, a tendência estatística observada para uma maior frequência do alelo Gly16 nos indivíduos com a presença de BIE pode ser considerado indício da influência de polimorfismos no gene ADBR2 no BIE em adolescentes.

Korean Asthma Guideline 2014: Summary of Major Updates to the Korean Asthma Guideline 2014 / 결핵및호흡기질환

Asthma is a prevalent and serious health problem in Korea. Recently, the Korean Asthma Guideline has been updated by The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) in an effort to improve the clinical management of asthma. This guideline focuses on adult patients with asthma and aims to deliver up to date scientific evidence and recommendations to general physicians for the management of asthma. For this purpose, this guideline was updated following systematic review and meta-analysis of recent studies and adapting some points of international guidelines (Global Initiative for Asthma [GINA] report 2014, National Asthma Education and Prevention Program [NAEPP] 2007, British Thoracic Society [BTS/SIGN] asthma guideline 2012, and Canadian asthma guideline 2012). Updated issues include recommendations derived using the population, intervention, comparison, and outcomes (PICO) model, which produced 20 clinical questions on the management of asthma. It also covers a new definition of asthma, the importance of confirming various airflow limitations with spirometry, the epidemiology and the diagnostic flow of asthma in Korea, the importance and evidence for inhaled corticosteroids (ICS) and ICS/formoterol as a single maintenance and acute therapy in the stepwise management of asthma, assessment of severity of asthma and management of exacerbation, and an action plan to cope with exacerbation. This guideline includes clinical assessments, and treatment of asthma-chronic obstructive pulmonary disease overlap syndrome, management of asthma in specific conditions including severe asthma, elderly asthma, cough variant asthma, exercise-induced bronchial contraction, etc. The revised Korean Asthma Guideline is expected to be a useful resource in the management of asthma.

The association of forced expiratory volume in one second and forced expiratory flow at 50% of the vital capacity, peak expiratory flow parameters, and blood eosinophil counts in exercise-induced bronchospasm in children with mild asthma

BACKGROUND: Exercise-induced bronchoconstriction (EIB), which describes acute airway narrowing that occurs as a result of exercise, is associated with eosinophilic airway inflammation, bronchial hyperresponsiveness. The forced expiratory volume in one second (FEV₁) is the most commonly used spirometric test in the diagnosis of EIB in exercise challenge in asthma. Other parameters such as forced expiratory flow at 50% of the vital capacity (FEF(50%)) and peak expiratory flow (PEF) are used less often in the diagnosis of EIB. OBJECTIVE: The purpose of this study is to evaluate the association of FEV₁ and FEF(50%), PEF parameters, blood eosinophil counts in EIB in children with mild asthma. METHODS: Sixty-seven children (male: 39, female: 28) with mild asthma were included in this study. Pulmonary functions were assessed before and at 1, 5, 10, 15, and 20 minutes after exercise. The values of spirometric FEV₁, FEF50(%), PEF, and blood eosinophil counts were evaluated in EIB in children with mild asthma. RESULTS: There was a positive correlation between FEV₁ with FEF(50%) and PEF values (p < 0.05; FEF(50%), r=0.68; PEF, r=0.65). Also, a positive correlation was found between blood eosinophil counts and the values of spirometric FEV₁, FEF(50%), and PEF (p < 0.05; FEV₁, r=0.54; FEF(50%), r=0.42; PEF, r=0.26). In addition to these correlations, in the exercise negative group for FEV₁, the FEF(50%) and PEF values decreased more than the cutoff values in 3, and 2 patients, respectively. CONCLUSION: According to the presented study, eosinophil may play a major role in the severity of EIB in mild asthma. FEF(50%) and PEF values can decrease in response to exercise without changes in FEV₁ in mild asthmatic patients.

The role of leukotriene modifier in pediatric allergic disease

Leukotriene (LT) modifiers are composed of leukotriene receptor antagonists and 5-lipoxygenase inhibitors. LTs, C4, D4, and E4 are collectively termed cysteinyl LTs and best are the characterized receptors for cysLTs are cysLT1 and cysLT2. cysLT1 ligation mediates sustained bronchial contraction, mucosal secretion, and edema, which are central to the pathogenesis of asthma. cysLT2 ligation is thought to contribute to edema, inflammation, and tissue fibrosis in asthma. LT modifiers attenuate bronchoconstriction responses and exert anti-inflammatory effects, reflected by reduced eosinophil counts in the peripheral blood, sputum, and bronchoalveolar lavage fluid of asthmatic patients. Inhaled corticosteroids are generally superior to LT modifiers as a first-line controller. However, LT modifiers are easy to administer, have good compliance, and have excellent safety. LT modifiers are recommended for asthmatic children aged < or =5 years as a first-line controller. The Japanese Guideline for Childhood Asthma recommends LT modifiers, as a first-line controller prior to inhaled corticosteroid for children aged <2 years. LT modifiers can improve asthma control as add-on therapy with ICS. They can also be effective for exercise-induced asthma. LT modifiers are recommended for the treatment of allergic rhinitis in combination with H1-antihistamines or as a first-line drug for patients who cannot or do not wish to use intranasal corticosteroids. LT modifiers can also be considered for add-on therapy in the treatment of chronic urticaria, atopic dermatitis, and other allergic diseases.

Prevalência dos sintomas de asma e alergia e avaliação dos mecanismos envolvidos no broncoespasmo induzido pelo exercício em corredores de longa distância / Prevalence of asthmatic and allergic symptoms and mechanism of exercise-induced bronchoconstriction in long distance runners

A prevalência de sintomas de asma, broncoespasmo induzido pelo exercício (BIE), hiperresponsividade brônquica (HRB) e alergia em atletas que praticam modalidades de alto rendimento e longa duração tem aumentado nas últimas décadas e tem sido estudada principalmente em atletas de inverno e nadadores. No entanto, a prevalência de sintomas de asma e alergia e os mecanismos inflamatórios envolvidos no BIE que ocorre em corredores de longa distância permanecem pouco conhecidos. Objetivos: O presente estudo tem como objetivo avaliar a prevalência de sintomas de asma e alergia em corredores de longa distância de elite e investigar os mecanismos inflamatórios envolvidos no BIE nos atletas sem histórico de asma. Casuística e Métodos: Este estudo foi realizado em duas fases: na Fase I, foi avaliada a prevalência de sintomas de asma e alergia em 201 corredores de longa distância, através da aplicação dos questionários ISAAC e AQUA©. Na Fase II, foram avaliados os mecanismos inflamatórios envolvidos no BIE de 40 corredores que não apresentaram sintomas de asma na Fase I e que foram selecionados aleatoriamente. Nesta fase, os atletas compareceram ao laboratório em três momentos, com intervalo máximo de duas semanas entre cada visita, e foram submetidos às seguintes avaliações 1º) escarro induzido e teste cardiopulmonar máximo, 2º) broncoprovocação por metacolina e, 3º) óxido nítrico no ar exalado (FeNO), metabólitos LTE4 e 9alfa, 11beta-PGF2 e teste de hiperventilação eucápnica voluntária (HEV). Resultados: A prevalência de sintomas de asma e alergia foi de 6,5% e 60,5%, respectivamente. Ao analisar as questões do AQUA©, observou-se alta frequência de sintomas de BIE (62,3%) e rinite (56,6%). Os sintomas de alergia não foram associados a variáveis como gênero, idade, experiência em corridas de longa distância, volume de treinamento semanal e desempenho em provas de meia maratona e maratona. Verificou-se ainda que a prevalência de BIE foi de 27,5%. Quando comparados os...

An increased prevalence of asthma and allergic symptoms, exercise-induced bronchoconstriction (EIB) and bronchial hyperresponsiveness (BHR) has been observed in elite and endurance athletes, especially winter sports athletes and swimmers. However, the occurrence of allergy symptoms and the inflammatory mechanisms involved in the EIB that occurs in long distance runners remains poorly known. Objectives: the aims of the present study were to assess the prevalence of symptoms of asthma and allergy in long distance runners and to investigate possible inflammatory mediators involved in the EIB that occurs in those without asthma history. Methods: This cross sectional study was performed in two phases. In Phase I, the prevalence of symptoms of asthma and allergy was assessed in 201 long distance runners using ISAAC and AQUA© questionnaires. In Phase II, 40 athletes were randomly selected among those who did not present asthma history and they performed the following measurements: induced sputum, cardiopulmonary exercise testing, methacholine bronchoprovocation challenge, exhaled nitric oxide (FeNO), urinary collection to quantify LTE4 and 9alfa, 11beta-PGF2 metabolites and eucapnic voluntary hyperventilation test (EVH). Results: The prevalence of asthma and allergy symptoms was 6.5% and 60.5%, respectively. In addition, we observed a high frequency of EIB symptoms (62.3%) and rhinitis (56.6%). Allergy symptoms were not associated with anthropometric characteristics, running experience, weekly training volume and best half-marathon and marathon performance. The prevalence of EIB was 27.5% and no difference in baseline lung function, anthropometric data as well as training and performance characteristics was observed between athletes with (EIB+) and without (EIB-) EIB. EIB+ athletes reported more allergy symptoms (p=0.03) and were more resposive to methacholine (p=0.01) than EIB- athletes. A higher percentage of eosinophils in the induced sputum (p=0.03) and...

Beta 2 agonistas en deportistas. ¿Una ayuda ergogénica? / Beta 2 agonists in athletes. An ergogenic aid?

El asma es una condición crónica de las vías aéreas con hiperreactividad bronquial y broncoconstricción. El ejercicio puede desencadenar los síntomas asmáticos, lo que se conoce como broncoespasmo inducido por el ejercicio (BIE). El asma es común en atletas olímpicos, por lo cual los deportistas utilizan los medicamentos β2 agonistas para prevenir y tratar los episodios de asma. Estos fármacos se suministran preferiblemente por inhalación. En el deporte, los β2 agonistas están restringidos por la regulación antidopaje, con base en que estos medicamentos tienen el potencial de mejorar el rendimiento físico, lo que puede resultar en una ventaja competitiva. Los β2 agonistas están prohibidos por la WADA (World Anti-doping Agency), con excepción del salbutamol (con suministro máximo permitido de 1.600 µg en 24 horas) y el salmeterol inhalado. Estos fármacos, administrados por vía oral, pueden tener efectos ergogénicos en los deportistas. Se ha documentado que administrado por esta vía el salbutamol puede mejorar el rendimiento en disciplinas de resistencia, aumentar la fuerza muscular y mejorar la potencia anaeróbica. Sin embargo, según la evidencia científica, los β2 agonistas inhalados no tienen un efecto relevante de aumento en el rendimiento en deportistas no asmáticos.

Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB). Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency), except salbutamol (maximum dose: 1.600 µg over 24 hours) and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

Seasonal Variation in Skin Sensitivity to Aeroallergens

PURPOSE: We previously demonstrated seasonal variation in sensitization to aeroallergens in a small group of patients with exercise-induced asthma. This study was performed to confirm the relationship in a much larger population. METHODS: The charts of 1,891 patients who received allergy skin prick tests were reviewed retrospectively. The test results from subjects aged < or =60 years were compared between the groups classified according to the season when the patients received the tests (spring: March-May, summer: June-August, fall: September-November, winter: December-February). The data from 25 respiratory allergy patients who received the tests two or more times and showed a positive response at least once were analyzed longitudinally. RESULTS: The most prevalent among 29 tested aeroallergens were house dust mites (HDMs) Dermatophagoides pteronyssinus and D. farinae. The skin sensitization rates to D. pteronyssinus (23.2% vs. 32.1%, P=0.004) and D. farinae (22.2% vs. 30.2%, P=0.009) were significantly lower in the summer and higher in the fall (38.3% vs. 26.6% and 35.6% vs. 25.3%; P=0.001 respectively) than those in other seasons in patients with a respiratory allergy (n=1,102). The sensitization rates to weed pollens in the fall (13.9% vs. 8.3%, P=0.006) and to Aspergillus fumigatus in the winter (2.9% vs. 0.7%, P=0.005) were significantly higher. In patients with non-respiratory allergy such as urticaria/anaphylaxis (n=340), the D. farinae sensitization rate was significantly lower in the summer also but higher in the spring. The trend of the HDM sensitization rate being lower in the summer and higher in the fall was observed in the longitudinal study. CONCLUSIONS: Skin sensitivity to aeroallergens such as HDMs, pollens, and molds demonstrates seasonal variation in respiratory allergy patients. Non-respiratory allergy patients also showed seasonal variation in sensitivity to aeroallergens, which might be related to the "priming" effect of allergens.

Montelukast / Montelukast

Forma farmacéutica: tableta. Denominación común internacional: montelukast sódico.Composición: cada tableta contiene 10 mg de montelukast sódico, lactosa.Categoría farmacológica: antagonista de los leucotrienos (categorías farmacológicas).Farmacocinética: la concentración plasmática máxima se alcanza entre 2-4 horas después de su administración por vía oral con una biodisponibilidad del 64 por ciento. La absorción no se ve modificada por la ingestión de los alimentos. La unión a proteínas plasmáticas es del 99 por ciento .Se metaboliza de forma extensa en el hígado por las isoenzimas CYP3A4, CYP2A6 y CYP2C9 del citocromo P450. La semivida de eliminación del montelukast es de 2,7 a 5,5 horas, siendo eliminado, conjuntamente con sus metabolitos casi exclusivamente por vía biliar a través de las heces. Su metabolismo disminuye y su semivida de eliminación aumenta en presencia de disfunción hepática moderada. La farmacocinética es similar en pacientes jóvenes o ancianos y no es afectada por la insuficiencia renal.Indicaciones: asma persistente leve a moderada en pacientes no controlados adecuadamente con corticoides inhalados y beta-2 de acción corta a demanda. Profilaxis de asma cuyo componente principal es la broncoconstricción inducida por el ejercicio. Alivio sintomático de la rinitis alérgica estacional en pacientes asmáticos.Contraindicaciones: hipersensibilidad al montelukast.Uso en poblaciones especiales: ver información adicional en precauciones. Niño: se desconoce la eficacia y seguridad en esta población. LM: evitar, datos no disponibles. E: categoría de riesgo B. DH: usar con cautela.Precauciones: no es efectivo en el ataque agudo de....

Broncoespasmo induzido por exercício em corredores brasileiros de longa distância de elite / Exercise-induced bronchoconstriction in elite long-distance runners in Brazil

OBJETIVO: Determinar a prevalência de broncoespasmo induzido por exercício em corredores brasileiros de longa distância de elite e se há uma diferença na carga de treinamento entre atletas com e sem broncoespasmo induzido por exercício. MÉTODOS: Estudo transversal com corredores de longa distância de elite sem sintomas atuais de asma e sem diagnóstico de broncoespasmo induzido por exercício. Todos os participantes foram submetidos ao teste de hiperventilação voluntária eucápnica e ao teste cardiopulmonar de esforço máximo e responderam a questionários sobre sintomas de asma e atividade física para monitorizar sua carga de treinamento semanal. RESULTADOS: Dos 86 atletas do sexo masculino recrutados, 20 concordaram em participar do estudo, dos quais 5 (25%) foram diagnosticados com broncoespasmo induzido por exercício. Não foram evidenciadas diferenças entre os atletas com e sem broncoespasmo induzido por exercício em relação a características antropométricas, consumo de oxigênio de pico, valores basais de função pulmonar ou sintomas de asma relatados. A carga de treinamento semanal foi significativamente menor nos atletas com broncoespasmo induzido por exercício do que naqueles sem esse diagnóstico. CONCLUSÕES: Nesta amostra de corredores de longa distância brasileiros, a prevalência de broncoespasmo induzido por exercício foi alta.

OBJECTIVE: To determine the prevalence of exercise-induced bronchoconstriction among elite long-distance runners in Brazil and whether there is a difference in the training loads among athletes with and without exercise-induced bronchoconstriction. METHODS: This was a cross-sectional study involving elite long-distance runners with neither current asthma symptoms nor a diagnosis of exercise-induced bronchoconstriction. All of the participants underwent eucapnic voluntary hyperpnea challenge and maximal cardiopulmonary exercise tests, as well as completing questionnaires regarding asthma symptoms and physical activity, in order to monitor their weekly training load. RESULTS: Among the 86 male athletes recruited, participation in the study was agreed to by 20, of whom 5 (25%) were subsequently diagnosed with exercise-induced bronchoconstriction. There were no differences between the athletes with and without exercise-induced bronchoconstriction regarding anthropometric characteristics, peak oxygen consumption, baseline pulmonary function values, or reported asthma symptoms. The weekly training load was significantly lower among those with exercise-induced bronchoconstriction than among those without. CONCLUSIONS: In this sample of long-distance runners in Brazil, the prevalence of exercise-induced bronchoconstriction was high.