Comparative effects of aerobic, combined, and intermittent exercise in children and adolescents with asthma: a systematic review / Efeitos comparativos dos exercícios aeróbicos, combinados e intermitentes em crianças e adolescentes com asma: uma revisão sistemática

Asthma is a chronic disease with a heterogeneous pathogenesis and etiology. Inflammation is considered one of the main triggers of bronchospasm and airway obstruction, which lead to clinical manifestations. Exercise is encouraged as a way to avoid cardiovascular, musculoskeletal, and psychosocial disorders and help control the disease. Our objective was to analyze the comparative effects of aerobic, combined (resistance and aerobic), and intermittent exercise on the functional capacity, lung function, and quality of life of children and adolescents with asthma, as well as to identify the relationship between exercise, other functional parameters, and inflammatory components characteristic of asthma. This was a systematic review of randomized clinical trials involving asthmatic populations aged between 6 and 17 years. PEDro, Lilacs, PubMed, and Cochrane Library/Central were searched for studies published in the last 10 years in English or Portuguese. We identified 8136 references, of which only 3 met the eligibility criteria. Considering the intervention time, aerobic exercise showed better functional capacity results. Regarding the common parameters used to assess lung function, intermittent exercise was the only type to result in significant change. Regarding quality of life, intermittent exercise had superior results, while combined exercise stood out for musculoskeletal improvement. Exercise can be a good non-pharmacological strategy for reducing the consequences of this pathology.

A asma é uma doença crônica, com patogênese e etiologia heterogêneas. Considera-se o quadro inflamatório como um dos principais desencadeantes do broncoespasmo e obstrução das vias aéreas, os quais levam às manifestações clínicas. Sugerese que os exercícios físicos sejam uma terapêutica importante para evitar distúrbios cardiovasculares, musculoesqueléticos e psicossociais, e ajudar no controle da doença. O objetivo deste estudo é analisar os efeitos comparativos dos exercícios físicos aeróbicos, combinados (resistência e aeróbico) e intermitentes na capacidade funcional, função pulmonar e qualidade de vida das crianças e adolescentes com asma, identificando também as possíveis relações dos exercícios com outros parâmetros funcionais e componentes inflamatórios característicos da asma. As fontes de buscas utilizadas foram PEDro, LILACS, PubMed e Cochrane Library/Central, dos quais selecionou-se apenas ensaios clínicos randomizados, em crianças e adolescentes com o diagnóstico de asma, com idade entre 6 e 17 anos, publicados nos últimos dez anos, nas línguas inglesa e portuguesa. Foram identificadas 8.136 referências, sendo que destas, apenas três preencheram os critérios de inclusão. Considerando o tempo de intervenção, o exercício aeróbico apresentou melhores resultados referente à capacidade funcional. Em relação ao parâmetro comum utilizado para avaliar a função pulmonar, o exercício intermitente foi o único a obter alterações significativas. Quanto à qualidade de vida, o exercício intermitente obteve resultados superiores, e os exercícios combinados destacam-se pela melhora musculoesquelética. A prática de exercícios físicos pode ser uma boa estratégia, não farmacológica, para reduzir as consequências desta patologia.

Prenatal stress induces long-lasting effects in lung glucocorticoid receptor gene expression in a sex-dependent manner / O estresse pré-natal induz efeitos de longo prazo na expressão gênica de receptores de glicocorticoides no pulmão de uma maneira dependente do sexo

AIM: Stressful events during pregnancy may influence respiratory system development, resulting in long-term effects in the offspring. However, little is known on its long-lasting effects upon the expression of important genes in the lungs. Thus, we aimed to evaluate the effect of two different prenatal stress paradigms on lung glucocorticoid receptor (GR) expression in adulthood. METHODS: Pregnant BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). In both groups (PNS1 and PNS2), restraint stress was used. When adults, male and female offspring were submitted to 30 min of restraint stress. Lung gene expression of GR was evaluated. RESULTS: There was a significant increase in GR expression in males (PNS1), under basal conditions. Restraint stress during adulthood significantly reduced GR expression in PNS1 and PNS2 males as compared to controls. No significant differences were found for females. CONCLUSION: Results indicate that prenatal stress from the second week of gestation modulates adult male mice GR expression in the lungs. Thus, fetal exposure to maternal stress from the second week of gestation seems to modulate mechanisms responsible for pulmonary development in a sex-dependent manner.

OBJETIVO: Eventos estressores durante a gestação podem influenciar o desenvolvimento do sistema respiratório, resultando em efeitos a longo prazo na prole. No entanto, pouco se sabe sobre seus efeitos duradouros sobre a expressão de genes importantes nos pulmões. Assim, nosso objetivo foi avaliar o efeito de dois diferentes modelos de estresse pré-natal na expressão pulmonar do receptor de glicocorticoide (GR) na vida adulta. MÉTODOS: Camundongos BALB/c prenhes foram divididas em 3 grupos: controle (CON), estresse pré-natal a partir da segunda semana de gestação (PNS1) e estresse pré-natal durante a última semana de gestação (PNS2). Nos dois grupos (PNS1 e PNS2), o estresse por contenção foi utilizado. Quando adultas, as proles machos e fêmeas foram submetidas ao estresse por contenção durante 30 min. A expressão do gene GR no pulmão foi avaliada. RESULTADOS: Houve um aumento significativo na expressão de GR em machos (PNS1) sob condições basais. O estresse na vida adulta reduziu significativamente a expressão de GR em machos PNS1 e PNS2 em comparação aos controles. Não foram encontradas diferenças significativas em fêmeas. CONCLUSÃO: Os resultados indicam que o estresse pré-natal a partir da segunda semana de gestação modula a expressão do GR nos pulmões de camundongos machos adultos. Assim, a exposição fetal ao estresse materno a partir da segunda semana de gestação parece modular os mecanismos responsáveis pelo desenvolvimento pulmonar de uma maneira dependente do sexo.

Protective effect of early prenatal stress on the induction of asthma in adult mice: Sex-specific differences.

Adversities faced during the prenatal period can be related to the onset of diseases in adulthood. However, little is known about the effects on the respiratory system. This study aimed to evaluate the effects of prenatal stress in two different time-points during pregnancy on pulmonary function and on the inflammatory profile of mice exposed to an asthma model. Male and female BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). Both PNS1 and PNS2 pregnant females were submitted to restraint stress. As adults, fear/anxiety behaviors were assessed, and animals were subjected to an asthma model induced by ovalbumin. Pulmonary function, inflammatory parameters in bronchoalveolar lavage (BAL) and histology were evaluated. There was a significant decrease in the number of entries and time spent in the central quadrant on the open field test for the PNS1 animals. Females (PNS1) showed improved pulmonary function (airway resistance, tissue damping and pulmonary elastance), significant increase in the percentage of neutrophils and lymphocytes and a decrease in eosinophils when compared to controls. There was a significant decrease in inflammatory cytokines in BAL of both males (IL-5 and IL-13) and females (IL-4, IL-5 and IL-13) from PNS1 and PNS2 when compared to the CON group. Prenatal stress starting from the beginning of pregnancy reduces the impact of asthma development in adult female mice, showing an improved pulmonary function and a lower inflammatory response in the lungs.

Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model.

BACKGROUND: Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. OBJECTIVE: To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. METHODS: Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (chronic protocol). Twenty-four hours after the last intranasal challenge, bronchoalveolar lavage fluid (BALF) was performed for total and differential cells count, cytokine analysis, and eosinophil peroxidase activity. Lung tissue was also removed for histopathologic analysis. RESULTS: Tp extract has shown a significant increase in total cells count from BALF as well as an increase in absolute eosinophils count, eosinophil peroxidase activity, interleukin (IL)-5 and IL-13 levels, in both acute and chronic protocols. Peribronchovascular infiltrate, goblet cells hyperplasia and collagen deposition were shown in the airways of acute and chronic Tp-exposed mice. CONCLUSION: Our data suggest that the intranasal exposure to Tp extract, with no systemic sensitization and no use of adjuvants, induces a robust allergic inflammation in the lungs of mice, in both acute and chronic models. Our Tp extract seems to be a potent allergen extract which may be used in asthma model studies.

Recombinant human deoxyribonuclease attenuates oxidative stress in a model of eosinophilic pulmonary response in mice.

The inflammatory cells infiltrating the airways produce several mediators, such as reactive oxygen species (ROS). ROS and the oxidant-antioxidant imbalance might play an important role in the modulation of airways inflammation. In order to avoid the undesirable effects of ROS, various endogenous antioxidant strategies have evolved, incorporating both enzymatic and non-enzymatic mechanisms. Recombinant human deoxyribonuclease (rhDNase) in clinical studies demonstrated a reduction in sputum viscosity, cleaving extracellular DNA in the airways, and facilitating mucus clearance, but an antioxidant effect was not studied so far. Therefore, we evaluated whether the administration of rhDNase improves oxidative stress in a murine model of asthma. Mice were sensitized by two subcutaneous injections of ovalbumin (OVA), on days 0 and 7, followed by three lung challenges with OVA on days 14, 15, and 16. On days 15 and 16, after 2 h of the challenge with OVA, mice received 1 mg/mL of rhDNase in the lungs. Bronchoalveolar lavage fluid and lung tissue were obtained on day 17, for inflammatory and oxidative stress analysis. We showed that rhDNase did not alter the population of inflammatory cells, such as eosinophil cells, in OVA-treated rhDNase group but significantly improved oxidative stress in lung tissue, by decreasing oxygen reactive species and increasing superoxide dismutase/catalase ratio, glutathione peroxidase activity, and thiol content. Our data provide the first evidence that rhDNase decreases some measures of oxidative stress and antioxidant status in a murine model of asthma, with a potential antioxidant effect to be further studied in human asthma.

Clinical characteristics of children and adolescents with severe therapy-resistant asthma in Brazil.

OBJECTIVE: To describe the clinical characteristics, lung function, radiological findings, and the inflammatory cell profile in induced sputum in children and adolescents with severe therapy-resistant asthma (STRA) treated at a referral center in southern Brazil. METHODS: We retrospectively analyzed children and adolescents (3-18 years of age) with uncontrolled STRA treated with high-dose inhaled corticosteroids and long-acting ß2 agonists. We prospectively collected data on disease control, lung function, skin test reactivity to allergens, the inflammatory cell profile in induced sputum, chest CT findings, and esophageal pH monitoring results. RESULTS: We analyzed 21 patients (mean age, 9.2 ± 2.98 years). Of those, 18 (86%) were atopic. Most had uncontrolled asthma and near-normal baseline lung function. In 4 and 7, induced sputum was found to be eosinophilic and neutrophilic, respectively; the inflammatory cell profile in induced sputum having changed in 67% of those in whom induced sputum analysis was repeated. Of the 8 patients receiving treatment with omalizumab (an anti-IgE antibody), 7 (87.5%) showed significant improvement in quality of life, as well as significant reductions in the numbers of exacerbations and hospitalizations. CONCLUSIONS: Children with STRA present with near-normal lung function and a variable airway inflammatory pattern during clinical follow-up, showing a significant clinical response to omalizumab. In children, STRA differs from that seen in adults, further studies being required in order to gain a better understanding of the disease mechanisms.

Clinical characteristics of children and adolescents with severe therapy-resistant asthma in Brazil / Características clínicas de crianças e adolescentes brasileiros com asma grave resistente a terapia

AbstractObjective: To describe the clinical characteristics, lung function, radiological findings, and the inflammatory cell profile in induced sputum in children and adolescents with severe therapy-resistant asthma (STRA) treated at a referral center in southern Brazil.Methods: We retrospectively analyzed children and adolescents (3-18 years of age) with uncontrolled STRA treated with high-dose inhaled corticosteroids and long-acting β2 agonists. We prospectively collected data on disease control, lung function, skin test reactivity to allergens, the inflammatory cell profile in induced sputum, chest CT findings, and esophageal pH monitoring results.Results: We analyzed 21 patients (mean age, 9.2 ± 2.98 years). Of those, 18 (86%) were atopic. Most had uncontrolled asthma and near-normal baseline lung function. In 4 and 7, induced sputum was found to be eosinophilic and neutrophilic, respectively; the inflammatory cell profile in induced sputum having changed in 67% of those in whom induced sputum analysis was repeated. Of the 8 patients receiving treatment with omalizumab (an anti-IgE antibody), 7 (87.5%) showed significant improvement in quality of life, as well as significant reductions in the numbers of exacerbations and hospitalizations.Conclusions: Children with STRA present with near-normal lung function and a variable airway inflammatory pattern during clinical follow-up, showing a significant clinical response to omalizumab. In children, STRA differs from that seen in adults, further studies being required in order to gain a better understanding of the disease mechanisms.

ResumoObjetivo: Descrever as principais características clínicas, a função pulmonar, as características radiológicas e o perfil inflamatório do escarro induzido de crianças e adolescentes com asma grave resistente a terapia (AGRT) tratados em um centro de referência do sul do Brasil.Métodos: Foram analisadas retrospectivamente crianças e adolescentes de 3-18 anos com diagnóstico de AGRT não controlada acompanhados durante pelo menos 6 meses e tratados com doses elevadas de corticoide inalatório associado a um β2-agonista de longa duração. Foram coletados prospectivamente dados relativos ao controle da doença, função pulmonar, teste cutâneo para alérgenos, perfil inflamatório do escarro induzido, TC de tórax e pHmetria esofágica.Resultados: Foram analisados 21 pacientes (média de idade: 9,2 ± 2,98 anos). Dos 21, 18 (86%) eram atópicos. A maioria apresentava asma não controlada e função pulmonar basal próxima do normal. Em 4 e 7 pacientes, o escarro induzido revelou-se eosinofílico e neutrofílico, respectivamente, e 67% dos pacientes que repetiram o exame apresentaram mudança no perfil inflamatório. Dos 8 pacientes que receberam omalizumabe (um anticorpo anti-IgE), 7 (87,5%) apresentaram melhora importante da qualidade de vida, com redução importante das exacerbações e hospitalizações.Conclusões: Crianças com AGRT apresentam função pulmonar próxima do normal e padrão inflamatório das vias aéreas variável durante o seguimento clínico, com importante resposta clínica ao omalizumabe. A AGRT em crianças difere da AGRT em adultos, e são necessários mais estudos para esclarecer os mecanismos da doença.

Equações internacionais superestimam a força muscular ventilatória em crianças e adolescentes com fibrose cística / International equations overestimate the respiratory muscle strength in children and adolescents with cystic fibrosis / Ecuaciones internacionales sobreestiman la fuerza muscular ventilatoria en niños y adolescentes con fibrosis quística

O objetivo deste estudo foi comparar os resultados da normalização dos dados de força muscular ventilatória utilizando-se três equações de referência internacionais e uma nacional em crianças e adolescentes com fibrose cística (FC). Estudo retrospectivo, no qual foram incluídos pacientes com FC, idade entre 8 e 12 anos e acompanhamento ambulatorial regular. Foram coletados dados demográficos e variáveis antropométricas. Todos os pacientes incluídos deveriam ter realizado teste de força muscular ventilatória e espirometria nos últimos 12 meses. A normalização dos resultados foi realizada utilizando-se as variáveis preditoras requeridas em cada equação estudada. Os dados foram comparados utilizando-se uma ANOVA de uma via. Foram incluídos 24 pacientes, 62,5% masculinos, média de idade 10,5±1,53 anos, estatura 138,0±0,08 cm, massa corporal 34,6±9,07 kg, VEF1 93,29±29,02% e CVF 103,78±26,12%. As pressões (cmH2O) inspiratória (PIMAX) e expiratória (PEMAX) máximas encontradas foram 92,1±22,8 e 98,9±24,5, respectivamente. Após a normalização pelas diferentes equações, demonstrou-se que as internacionais tendem a superestimar os achados para a nossa população. A equação nacional apresentou valores médios previstos significativamente (p<0,05) menores para PIMAX e PEMAX em comparação com as equações internacionais, sendo que estas classificariam a PIMAX como acima do normal (>100%) em 91,6, 79,1, e 75,0% dos sujeitos e a PEMAX em 66,6, 87,5 e 50%, enquanto a equação nacional estimaria apenas 50,0 e 37,5% dos indivíduos, respectivamente. A normalização dos resultados de força muscular ventilatória em crianças e adolescentes entre 8 e 12 anos com FC utilizando-se equações internacionais superestimam os valores das pressões respiratórias máximas...

The aim of the present study was to compare the results of standardization of ventilatory muscle strength data using three international reference values and one Brazilian reference in children and adolescents with cystic fibrosis (CF). This was a retrospective study, which included patients with CF aged 8 to 12 years and in regular follow-up at an outpatient facility. Demographic and anthropometric data were collected. All patients included in the sample should have had ventilatory muscle strength and lung function measured in the past 12 months. The standardization of the results was made using predicted values from each equation. Data were compared using one-way ANOVA. We included 24 patients, 62.5% males, with mean age of 10.5±1.53 years, height 138.0±0.08 cm, weight 34.6±7.9 kg, FEV1 93.29±29.02% and FVC 103.78±26.12%. The maximum inspiratory (MIP) and expiratory (MEP) pressures (cmH2O) observed were 92.1±22.8 and 98.9±24.5, respectively. After standardization by the different equations, we found that the international reference tend to overestimate the findings. The Brazilian equation showed values significantly lower (p<0.05) for MIP and MEP compared to international reference equations, and these would consider MIP values above normal (>100%) in 91.6, 79.1, and 75.0% of the subjects and MEP in 66.6, 87.5 and 50% of them, while using the national equation only 50.0 and 37.5% of subjects were above 100%, respectively. The results of standardization of ventilatory muscle strength in children and adolescents with CF aged 8 to 12 years using international equations overestimate the values of maximal respiratory pressures...

El objetivo de este estudio fue comparar los resultados de la normalización de los datos de fuerza muscular ventilatoria utilizando tres ecuaciones de referencia internacionales y una nacional en niños y adolescentes con fibrosis quística (FC). Estudio retrospectivo, en el cual fueron incluidos pacientes con FC, edad entre 8 y 12 años y control ambulatorio regular. Fueron colectados datos demográficos y variables antropométricas. Todos los pacientes incluidos deberían haber realizado test de fuerza muscular ventilatoria y espirometría en los últimos 12 meses. La normalización de los resultados fue realizada utilizando las variables predictoras requeridas en cada ecuación estudiada. Los datos fueron comparados utilizando una ANOVA de una vía. Fueron incluidos 24 pacientes, 62,5% masculinos, media de edad 10,5±1,53 años, estatura 138,0±0,08 cm, masa corporal 34,6±9,07 kg, VEF1 93,29±29,02% y CVF 103,78±26,12%. Las presiones (cmH2O) inspiratoria (PIMAX) y expiratoria (PEMAX) máximas encontradas fueron 92,1±22,8 y 98,9±24,5, respectivamente. Después de la normalización por las diferentes ecuaciones, se demostró que las internacionales tienden a sobreestimar los hallazgos para nuestra población. La ecuación nacional presentó valores medios previstos significativamente (p<0,05) menores para PIMAX y PEMAX en comparación con las ecuaciones internacionales, siendo que estas clasificarían la PIMAX como encima de lo normal (>100%) en 91,6, 79,1, y 75,0% de los sujetos y la PEMAX en 66,6, 87,5 y 50%, mientras la ecuación nacional estimaría apenas 50,0 y 37,5% de los individuos, respectivamente. La normalización de los resultados de fuerza muscular ventilatoria en niños y adolescentes entre 8 y 12 años con FC utilizando ecuaciones internacionales sobreestiman los valores de las presiones respiratorias máximas...