Bronchial asthma: today and tomorrow

A asma é caracterizada por obstrução reversível, inflamação e hiperreatividade brônquicas. O diagnóstico é baseado em informações clínicas e testes de função pulmonar. Os eosinófilos são uma característica importante da fisiopatologia da asma. Eles produzem fatores quimiotáxicos, broncoconstrictores e vasoativos, que conduzem à hiperreatividade brônquica. Além disso, os eosinófilos danificam o tecido circunvizinho, através da liberação do conteúdo protéico de seus grânulos. As recomendações para o tratamento da asma são baseadas em quatro componentes: uso de medidas objetivas da função pulmonar para avaliar a gravidade da asma e monitorar o curso da terapia; controle ambiental para evitar ou eliminar fatores precipitantes de sintomas ou crises; terapia farmacológica a longo prazo, para tratar e prevenir inflamação de via aérea e, também, para tratar as agudizações; e educação do paciente, criando uma parceria entre o paciente, a família e o clínico. Os b2-agonistas são a classe de drogas mais comumente usadas para o tratamento da asma. Usar essas drogas em demanda é freqüentemente mais aceito e recomendado. Em asma aguda, um b2-agonista é ainda o medicamento de escolha. Agonistas de ação prolongada, salmeterol e formoterol, podem diminuir sintomas de asma durante o dia e à noite. A teofilina, cujo uso esteve limitado pela toxicidade, pode recuperar uma posição importante no tratamento da asma, com a descoberta de suas ações antiinflamatórias. O brometo de ipratrópio, uma droga anticolinérgica, ainda espera um papel definido no tratamento da asma. Os corticoesteróides inalatórios têm efeitos mensuráveis nos sintomas, função pulmonar, reatividade brônquica e inflamação. Os efeitos colaterais limitam a administração sistêmica, mas não a administração tópica. Preparações mais novas, como budesonida, flunisolida e fluticasona diminuem a incidência de possíveis efeitos colaterais, porque têm uma melhor relação efeito tópico/efeito sistêmico. Medicamentos recentemente lançados incluem os antileucotrienos (anti-LTs), agentes que funcionam bloqueando a interação dos LTs com seus receptores (antagonistas de receptor) ou inibindo a síntese de LTs (inibidores de síntese). Representantes dos antagonistas são zafirlukast, pranlukast e montelukast. Pranlukast, o primeiro antagonista de receptor a ser comercializado, melhora função pulmonar e sintomas, dependendo da dose. Zileuton, um inibidor de síntese, demostrou melhorar a função pulmonar, reduzir sintomas, reduzir uso de b-agonistas e crises de asma. Esses efeitos positivos são dose-dependentes e anormalidades da função hepática parecem ser um limite relevante ao uso de zileuton, em alguns pacientes.Asthma is characterized by reversible obstruction, inflammation, and hyperreactivity of the airways. The diagnosis is based on clinical information and pulmonary function tests. Eosinophils are a main feature of the asthma pathophysiology. They produce bronchoconstrictor, chemotactic, and vasoactive products that lead to hyperreactivity. Also, they damage surrounding tissue, by releasing their cytotoxic granule content. The recommendations for the treatment of asthma were organized around four components of effective asthma management: use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy; environmental control measures to avoid or eliminate factors that precipitate asthma symptoms or exacerbations; comprehensive pharmacologic therapy for long-term management designed to reverse and prevent the airway inflammation characteristic of asthma as well as pharmacologic therapy to manage asthma exacerbations; and, patient education that foster a partnership among the patient, family, and clinicians. The b2-adrenergic agonists are the most commonly used class of drugs for the treatment of asthma. Using this drug on an as-needed basis is now more frequently accepted and recommended. In acute asthma, a b2-adrenergic agonist is still the medication of choice. Long-acting, salmeterol and formoterol, administered only twice daily, can decrease symptoms of asthma during day and nighttime. Theophylline, whose use has been limited by the potential for serious toxicity, may regain an important position in the asthma treatment with the development of the knowledge about its antiinflammatory actions. Dosing theophylline on a time-related basis also improves the risk/benefit ratio and makes theophylline a useful drug for nocturnal asthma. Ipratropium bromide, an anticholinergic drug, still awaits a defined role in the treatment of asthma. Corticosteroids, including inhaled forms, have measurable effects on symptoms, lung function, bronchial responsiveness, and inflammation associated with asthma. Side-effects of chronic use limit systemic administration, but not inhaled administration. Newer preparations, like budesonide, flunisolide, and fluticasone decrease the incidence of possible side-effects related to inhaled steroids by having better ratio of topical to systemic potency. Newly released medications include anti-leukotrienes (LTs) agents which function either by blocking the interaction of LTs with receptors (receptor antagonists) or by inhibiting leukotriene synthesis (synthesis inhibitors). Representatives of the antagonists discussed here are zafirlukast, pranlukast, and montelukast. Pranlukast, the first leukotriene receptor antagonist to be marketed, improves lung fuction and symptons when 450 mg b.i.d. is used. Zileuton, a leukotriene synthesis inhibitor, has been shown to improve lung fuction, reduce symptoms, reduce use b-agonists and asthma exacerbations. These positive effects are dose dependent and liver function abnormalities seem to be a relevant issue during zileuton use in some patients

Cough and dyspnea during bronchoconstriction: comparison of different stimuli

Abstract Background Bronchial challenge tests are used to evaluate bronchial responsiveness in diagnosis and follow-up of asthmatic patients. Challenge induced cough has increasingly been recognized as a valuable diagnostic tool. Various stimuli and protocols have been employed. The aim of this study was to compare cough and dyspnea intensity induced by different stimuli. Methods Twenty asthmatic patients underwent challenge tests with methacholine, bradykinin and exercise. Cough was counted during challenge tests. Dyspnea was assessed by modified Borg scale and visual analogue scale. Statistical comparisons were performed by linear mixed-effects model. Results For cough evaluation, bradykinin was the most potent trigger (p < 0.01). In terms of dyspnea measured by Borg scale, there were no differences among stimuli (p > 0.05). By visual analogue scale, bradykinin induced more dyspnea than other stimuli (p ≤ 0.04). Conclusion Bradykinin seems to be the most suitable stimulus for bronchial challenge tests intended for measuring cough in association with bronchoconstriction

Abordagem terapêutica na exacerbação da doença pulmonar obstrutiva crônica (DPOC)

Exacerbações de DPOC causam aumento da morbimortalidade, internação, piora da qualidade de vida e custos para o paciente e para o sistema de saúde. O paciente com DPOC apresenta, aproximadamente,duas a três exacerbações ao ano, principalmente no inverno, causando progressiva deterioração fisiológica e aumento da inflamação das vias aéreas. O tratamento se faz com broncodilatadores, corticosteróides, oxigenoterapia, ventilação mecânica e antibióticos, em alguns casos.Exacerbations of chronic obstructive pulmonary disease (COPD) cause increase in morbidity and mortality, hospital admissions, influence health-related quality of life and costs to the patient and health system. COPD patient experience 2 to 3 exacerbations per year, specially during winter, causing a progressive physiologic deterioration and increase in the airway inflammation. Treatment is based on bronchodilators, corticosteroids, oxygen therapy, mechanical ventilation and antibiotics

Bronchial asthma clinical approach

A asma é caracterizada por inflamação, obstrução reversível e hiperreatividade brônquica. Esta revisão objetiva oferecer aos estudantes de Medicina e médicos, recomendações para o atendimento do paciente asmático, de forma a mostrar as abordagens terapêuticas e sugerir uma proposta, reunindo opiniões de diferentes consensos.Asthma is characterized by inflammation, reversible bronchial obstruction and bronchial hyperresponsiveness. This review aimed to medical student and doctors offers guidelines for the asthmatic patient approach, in order to show therapeutic options and to suggest a therapeutic proposal involving different consensus reports

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding

Influence of risk factors on the long-term survival of oral rehabilitation with extra-narrow implants: a retrospective study

Objective: This study aimed to retrospectively collect clinical data to evaluate the influence of possible risk factors on the long-term success of implant treatment with extra-narrow (2.9 mm diameter) implants in a daily dental practice setting. Methodology: Data were collected from records of patients who received at least one extra-narrow implant from 2012 to 2017, regarding implant survival, prosthesis survival, patient characteristics, and implant characteristics. The association between the dependent variables “implant survival”, “prosthesis survival,” and “adverse events” related to patient and implant characteristics was statistically evaluated by chi-square tests. Moreover, implant and prosthesis survival were analyzed by Kaplan-Meier survival curves.&nbsp; Results: The sample was constituted of 58 patients (37 women and 21 men) with a mean age of 54.8 years old (SD: 12.5), followed up for up to eight years. In total, 86 extra-narrow implants were placed within this sample. Four implants were lost, resulting in an implant survival rate of 95.3%. A total of 55 prostheses were inserted and only one (1.8%) was lost, resulting in a prosthesis survival rate of 98.2%. The mean implant and prosthesis survival time was, respectively, 7.1 years and 6.3 years, according to the Kaplan-Meier survival analysis. A correlation was found between smoking and implant loss, which makes implant loss eight times more likely to occur in smokers than non-smokers. A significant association was also found between prosthesis loss and previous need of prosthesis repair. However, it was not considered clinically relevant. No association was found between the occurrence of adverse events and later implant or prosthesis loss. Conclusion: High implant and prosthesis survival rates were found in the long term for treatment with extra-narrow implants. Moreover, a significant correlation between smoking and implant loss was observed

Atopy risk factors at birth and in adulthood

OBJETIVO: Estudar a associação entre atopia e variáveis como peso, comprimento e nível socioeconômico no nascimento e na idade adulta jovem. MÉTODOS: Foram investigados 2.063 indivíduos em um estudo prospectivo de coorte de nascimento com indivíduos nascidos em Ribeirão Preto (SP), em 1978/1979, e examinados aos 23-25 anos de idade. Realizaram-se testes cutâneos de puntura (TCP) para oito alérgenos comuns no Brasil. Foram considerados atópicos os indivíduos que apresentaram reação papular > 3 mm para um ou mais dos oito alérgenos testados. A fim de avaliar a associação entre atopia e variáveis no nascimento e na idade adulta, utilizamos o modelo log-binomial (modelo linear generalizado). RESULTADOS: A prevalência de TCP positivo foi de 47,6%. O gênero masculino esteve associado a aumento do risco de atopia [risco relativo (RR) = 1,18; intervalo de confiança de 95% (IC95%) 1,07-1,30]. O baixo nível de escolaridade foi um fator de proteção contra atopia, com um RR = 0,74; IC95% 0,62-0,89. A convivência com um fumante na infância também esteve associada a um menor risco de atopia (RR = 0,87; IC95% 0,79-0,96). Peso e comprimento ao nascer, ordem de nascimento, idade materna e restrição de crescimento intrauterino não estiveram associados a TPC positivo. CONCLUSÕES: Este estudo demonstrou que o gênero masculino esteve associado a um aumento do risco de atopia. O baixo nível socioeconômico, estabelecido pelo baixo nível de escolaridade, foi um fator de proteção contra a atopia. Esses dados estão de acordo com a teoria da higiene.OBJECTIVE: To study the association between atopy and variables such as weight, length, and socioeconomic level at birth and in young adulthood. METHODS: A total of 2,063 subjects were investigated in a prospective birth cohort study of individuals born in Ribeirão Preto, Brazil, in 1978/1979, and examined at the age of 23-25 years. Skin prick tests (SPT) for eight common allergens in Brazil were performed. Subjects with a wheal reaction > 3 mm to one or more of the eight allergens tested were considered to be atopic. We used the log-binomial model (generalized linear model) in order to assess the association between atopy and birth or adult variables. RESULTS: The prevalence of positive SPT was 47.6%. Male gender was associated with an increased risk of atopy (relative risk [RR] = 1.18; 95% confidence interval [95%CI] 1.07-1.30). Low level of schooling was a protective factor against atopy, with a RR = 0.74; 95%CI 0.62-0.89. Living with a smoker in childhood was also associated with lower risk of atopy (RR = 0.87; 95%CI 0.79-0.96). Birth weight, length and order, maternal age, and intrauterine growth restriction were not associated with positive SPT. CONCLUSIONS: This study showed that male gender was associated with an increased risk of atopy. Low socioeconomic status, assessed by low level of schooling, was a protective factor against atopy. These data agree with the hygiene hypothesis

Exposure to high endotoxin concentration increases wheezing prevalence among laboratory animal workers: a cross-sectional study

Background: Endotoxin from Gram-negative bacteria are found in different concentrations in dust and on the ground of laboratories dealing with small animals and animal houses. Methods: Cross-sectional study performed in workplaces of two universities. Dust samples were collected from laboratories and animal facilities housing rats, mice, guinea pigs, rabbits or hamsters and analyzed by the "Limulus amebocyte lysate" (LAL) method. We also sampled workplaces without animals. The concentrations of endotoxin detected in the workplaces were tested for association with wheezing in the last 12 months, asthma defined by self-reported diagnosis and asthma confirmed by bronchial hyperresponsiveness (BHR) to mannitol. Results: Dust samples were obtained at 145 workplaces, 92 with exposure to animals and 53 with no exposure. Exposed group comprised 412 subjects and non-exposed group comprised 339 subjects. Animal-exposed workplaces had higher concentrations of endotoxin, median of 34.2 endotoxin units (EU) per mg of dust (interquartile range, 12.6-65.4), as compared to the non-exposed group, median of 10.2 EU/mg of dust (interquartile range, 2.6-22.2) (p < 0.001). The high concentration of endotoxin (above whole sample median, 20.4 EU/mg) was associated with increased wheezing prevalence (p < 0.001), i.e., 61 % of workers exposed to high endotoxin concentration reported wheezing in the last 12 months compared to 29 % of workers exposed to low endotoxin concentration. The concentration of endotoxin was not associated with asthma report or with BHR confirmed asthma. Conclusion: Exposure to endotoxin is associated with a higher prevalence of wheezing, but not with asthma as defined by the mannitol bronchial challenge test or by self- reported asthma. Preventive measures are necessary for these workers16CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçã

Influence of asthma definition on the asthma-obesity relationship

Background: Epidemiological studies suggest an association between obesity and asthma in adults and children. Asthma diagnosis criteria are different among studies. The aim of this study was to test the influence of asthma definition on the asthma-obesity relationship. Methods: In a cross-sectional analysis of 1922 men and women, subjects completed a translated questionnaire from the European Community Respiratory Health Survey and underwent spirometry and a bronchial challenge test. Weight, height and waist circumference were measured. Multiple logistic regression analysis was carried out to assess the association of variables related to obesity and asthma. Asthma was defined either by the presence of symptoms with bronchial hyperresponsiveness (BHR) or by a self-report of a physician-made diagnosis. The following variables were separately tested for associations with asthma: socioeconomic characteristics, schooling, physical activity, smoking status, anthropometry and spirometry. Results: No association was detected between asthma confirmed by BHR and obesity indicators, odds ratio (OR) = 1.08 (95% confidence interval: 0.69 - 1.68) for obesity assessed by body mass index &gt;= 30 kg/m(2); OR = 1.02 (0.74 - 1.40) for obesity assessed by abnormal waist-to-height ratio; and, OR = 0.96 (0.69 - 1.33) for abnormal waist circumference. On the contrary, a previous diagnosis of asthma was associated with obesity, OR = 1.48 (1.01 - 2.16) for body mass index &gt;= 30 kg/m(2); OR = 1.48 (1.13 - 1.93) for abnormal waist-to-height ratio; and, OR = 1.32 (1.00 - 1.75) for abnormal waist circumference. Female gender, schooling &gt;= 12 years and smoking were associated with BHR-confirmed asthma. Physically inactive subjects were associated with a previous diagnosis of asthma. Conclusions: Our findings indicate that the relationship between asthma and obesity in epidemiological studies depends on the definition adopted. Certain components of asthma, for instance, symptoms may be more prone to the obesity influence than other ones, like bronchial hyperresponsiveness.FAPESPFAPES