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Ultrastructure of Human Tracheal Smooth Muscle from Asthmatic and Non-asthmatic Subjects: Standardized Methods for Comparison.

830609516A characteristic feature of asthma is exaggerated airway narrowing, termed airway hyperresponsiveness (AHR) due to contraction of airway smooth muscle (ASM). Although smooth muscle-specific asthma susceptibility genes have been identified, it is not known whether asthmatic ASM is phenotypically different from non-asthmatic ASM in terms of subcellular structure or mechanical function.

The present study is the first to systematically quantify, using electron microscopy, the ultrastructure of tracheal SM from asthmatic and non-asthmatic subjects. Methodological details concerning tissue sample preparation, ultrastructural quantification, and normalization of isometric force by appropriate morphometric parameters are described. We reasoned that genetic and/or acquired differences in the ultrastructure of asthmatic ASM could be associated with functional changes.

We recently reported that asthmatic ASM is better able to maintain and recover active force generation after length oscillations simulating deep inspirations. The present study was designed to seek structural evidence to account for this observation. Contrary to our hypotheses, no significant qualitative or quantitative differences were found in the subcellular structure of asthmatic versus non-asthmatic tracheal smooth muscle. Specifically there were no differences in average smooth muscle cell cross-sectional area; fraction of the cell area occupied by non-filamentous area; amounts of mitochondria, dense bodies, and dense plaques; myosin and actin filament densities; basal lamina thickness; and the number of microtubules.

These results indicate that functional differences in ASM do not necessarily translate into observable structural changes.

Does migration affect asthma, rhinoconjunctivitis and eczema prevalence? Global findings from the international study of asthma and allergies in childhood.

Immigrants to Westernized countries adopt the prevalence of allergic diseases of native populations, yet no data are available on immigrants to low-income or low-disease prevalence countries. We investigated these questions using data from the International Study of Asthma and Allergies in Childhood.

METHODS: Standardized questionnaires were completed by 13-14-year-old adolescents and by the parent/guardians of 6-7-year-old children. Questions on the symptom prevalence of asthma, rhinoconjunctivitis and eczema, and a wide range of factors postulated to be associated with these conditions, including birth in or not in the country and age at immigration, were asked. Odds ratios for risk of the three diseases according to immigration status were calculated using generalized linear mixed models. These were adjusted for: world region; language and gross national income; and individual risk factors including gender, maternal education, antibiotic and paracetamol use, maternal smoking, and diet. Effect modification by gross national income and by prevalence was examined.

RESULTS: There were 326 691 adolescents from 48 countries and 208 523 children from 31 countries. Immigration was associated with a lower prevalence of asthma, rhinoconjunctivitis and eczema in both age groups than among those born in the country studied, and this association was mainly confined to high-prevalence/affluent countries. This reduced risk was greater in those who had lived fewer years in the host country.

CONCLUSIONS: Recent migration to high prevalence/affluent countries is associated with a lower prevalence of allergic diseases. The protective pre-migration environment quickly decreases with increasing time in the host country.

The challenge of objective confirmation of asthma diagnosis in primary care.

Asthma represents one of the most common chronic conditions encountered in primary care and diagnosis should be confirmed objectively with the demonstration of variable airflow obstruction. As many asthmatics have normal lung function at the time of clinical presentation, objective confirmation of airflow limitation may be challenging.

Fluctuations in airflow obstruction can be documented with simple office spirometry after bronchodilator challenge, home monitoring of peak expiratory flow and bronchoconstriction induced by spasmogens such as methacholine. We present a case highlighting the challenge of objective confirmation of asthma diagnosis in primary care and provide a critical review of the diagnostic approaches highlighted above.

Our aim is to provide a pragmatic interpretation of the available literature with a view to assisting clinicians in selecting the diagnostic test best suited for individualised patient encounters.

House dust mite sublingual immunotherapy is safe and appears to be effective in moderate, persistent asthma.

sitThe efficacy and safety of sublingual immunotherapy in house dust mite-induced asthma have yet to be firmly established. We report the results of a double-blind, placebo-controlled, randomized clinical trial performed in mainland China.

METHODS: After a three-month baseline period, 484 asthmatic adults were randomized 2 : 1 to 12 months of daily treatment with either an aqueous, standardized, 300 index of reactivity mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. The primary efficacy criterion was well-controlled asthma for at least 16 of the last 20 weeks of treatment.

RESULTS: In the active (n = 308) and placebo (n = 157) groups, well-controlled asthma was achieved by 85.4% and 81.5% of the patients, respectively (P = 0.244). A subsequent post hoc analysis by asthma severity revealed significant clinical benefits in actively treated subjects with moderate, persistent asthma at baseline [401-800 μg budesonide/day (n = 175)], with greater achievement of well-controlled asthma (80.5% and 66.1% for the active treatment and placebo groups, respectively; P = 0.021) and totally controlled asthma (54.0% and 33.9%, respectively, P = 0.008), a higher percentage of patients with an asthma control questionnaire score < 0.75 (56.6% and 40.0%, respectively; P = 0.039) and a greater mean reduction in inhaled corticosteroid use (218.5 μg and 126.2 μg, respectively; P = 0.004). The active vs placebo differences in disease control and corticosteroid use were not significant for mild, persistent asthma. No treatment-related serious adverse events were reported.

CONCLUSIONS: Sublingual mite allergen immunotherapy was well tolerated in adult asthmatics and effectively controlled disease in patients with moderate (but not mild) persistent asthma (ClinicalTrials.gov: NCT00660452).

Asthma Therapy and Its Effect on Airway Remodelling.

airway-in-asthmaAsthma remains a major health problem with significant morbidity, mortality and economic costs. In asthma, airway remodelling, which refers to all the microscopic structural changes seen in the airway tissue, has been recognised for many decades and remains one of the defining characteristics of the disease; however, it is still poorly understood.

The detrimental pathophysiological consequences of some features of remodelling, like increased airway smooth muscle mass and subepithelial fibrosis, are well documented. However, whether targeting these by therapy would be beneficial is unknown. Although the prevailing thinking is that remodelling is an abnormal response to persistent airway inflammation, recent evidence, especially from studies of remodelling in asthmatic children, suggests that the two processes occur in parallel.

The effects of asthma therapy on airway remodelling have not been studied extensively due to the challenges of obtaining airway tissue in the context of clinical trials. Corticosteroids remain the cornerstone of asthma therapy, and their effects on remodelling have been better studied than other drugs. Bronchial thermoplasty is the only asthma therapy to primarily target remodelling, although how it results in the apparent clinical benefits seen is not exactly clear.

In this article we discuss the mechanisms of airway remodelling in asthma and review the effects of conventional and novel asthma therapies on the process.

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