House dust mite allergen avoidance and self-management in allergic patients with asthma: randomised controlled trial

BACKGROUND: The efficacy of bed covers that are impermeable to house dust mites has been disputed. AIM: The aim of the present study was to investigate whether the combination of 'house dust mite impermeable' covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone. DESIGN OF STUDY: Prospective, randomised, double blind, placebo-controlled trial. SETTING: Primary care in a south-eastern region of the Netherlands. METHOD: Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intervention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms. RESULTS: One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups. CONCLUSION: House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone.     

Low-dose inhaled budesonide once or twice daily for 27 months in children with mild asthma

This study is an extended follow-up for 24 months of a 12-week trial to study the long-term clinical efficacy of low-dose inhaled budesonide (BUD) once or twice daily in children with mild asthma. A total of 122 children (mean age 9.7 years, girls/boys; 42/80) with mild asthma (FEV1 103.7% of predicted, reversibility in FEV1 3.5%, and fall in FEV1 after exercise 12.2%), not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. The children were treated with inhaled BUD 100 or 200 microg administered via Turbuhaler once daily in the morning, 100 microg twice daily, or placebo for 27 months. Exercise and methacholine challenges were performed at 3-month intervals the first year and at 6-month intervals the second year, in a total of seven visits. A significant dose-response effect favoring BUD 200 microg daily (vs 100 microg daily) was found when comparing changes in FEV1, FEF25%, and FEV50%; the fall in FEV1 after an exercise test; and the effect on blood eosinophils. Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 microg daily compared to placebo. Growth rate was not significantly affected except in children aged 7-11 years at baseline after 12 months of treatment. In conclusion, 100 or 200 microg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise-induced asthma and achieving nearly normal lung function. Baseline lung function was not significantly affected in this group of children with mild asthma.     

Corticosteroid enhances TNF‐α‐mediated leukocyte adhesion to pulmonary microvascular endothelial cells

Background: Some severe asthma patients are characterized by elevated levels of tumor necrosis factor alpha (TNF‐α) and neutrophilic inflammation in the airways. Although such phenotypic changes in asthma might contribute to corticosteroid refractoriness, the role of TNF‐α in the process remains unclear. TNF‐α exerts its biological effects mainly by acting on the vascular endothelium, and thereby upregulates leukocyte recruitment into inflamed tissues. The aim of this study was to investigate the effects of dexamethasone (DEX) on the TNF‐α‐mediated responses of human microvascular endothelial cells from lung blood vessels (HMVEC‐LBl) in vitro. Methods: HMVEC‐LBl were cultured with TNF‐α in the presence and absence of DEX. The effects of DEX on various TNF‐α‐mediated responses, such as the expressions of chemokines and cellular adhesion molecules, leukocyte adhesion were determined. Results: TNF‐α significantly induced growth‐related oncogene alpha (GRO‐α), interleukin 8 (IL‐8), regulated on activation, normal T‐cell expressed and secreted (RANTES) and interferon‐inducible protein 10 (IP‐10) productions and cell surface expressions of intracellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1) on HMVEC‐LBl. TNF‐α‐induced GRO‐α and IL‐8 were slightly attenuated by DEX treatment (reaches to 89% and 79%, respectively), whereas expressions of IP‐10, ICAM‐1 and VCAM‐1 were significantly enhanced by the same treatment (up to 172%, 152% and 139%, respectively). Correspondingly, in vitro adhesion of eosinophils and neutrophils to TNF‐α‐treated HMVEC‐LBl were significantly enhanced by DEX. Conclusions: Some proinflammatory effects of DEX, a corticosteroid, were found in TNF‐α‐mediated in vitro reactions of pulmonary microvascular endothelial cells, i.e. chemokine productions and leukocyte adhesion. These in vitro results may explain, at least in part, the corticosteroid refractoriness accompanied by a marked increase in TNF‐α production that is seen in severe asthmatic patients.     

Sleep disturbance and daytime symptoms in wheezing school-aged children

The aim of the study was to investigate whether wheezing is associated with disturbed sleep and increased daytime symptoms in school-aged children. A random sample of 1234 children, aged 6-14 years, participated in a respiratory health study in the region of Antwerp. The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed. In the children who wheezed in the last 12 months, sleep quality was more frequently disturbed due to nocturnal awakenings and restless sleep compared with children who did not wheeze. Daytime sleepiness and tiredness were more common in wheezing than in non-wheezing children. After adjusting for possible confounders a positive association was found between wheeze and: difficulties falling asleep [odds ratio (OR) = 2.0], restless sleep (OR = 5.0), daytime sleepiness (OR = 3.8) and daytime tiredness (OR = 5.1). Chronic cough (OR = 2.4), snoring (OR = 2.0), chronic rhinitis (OR = 2.6) and eczema (OR = 3.3) were associated with disturbed sleep. Chronic cough (OR = 2.5) and rhinitis (OR = 4.1) were related to daytime tiredness. Chronic rhinitis was an important risk factor for snoring (OR = 1.9). In wheezing school-aged children, decreased quality of sleep and increased daytime tiredness and sleepiness were more often reported. Upper airway symptoms were related to the sleep disturbances.     

Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin-induced asthma to threshold dose of aspirin

BACKGROUND: The exact mechanism of aspirin-induced asthma is not clear. It has been postulated that precipitation of asthma attacks by aspirin is linked to inhibition of COX activity and massive release of cysteinyl leukotriene into the airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for immunosuppression in organ transplantation and also for allergic diseases such as atopic dermatitis. OBJECTIVE: We evaluated the effects of tacrolimus in aspirin-induced asthma by using a double-blind, crossover study design. METHODS: Twelve patients with aspirin-induced asthma (male:female, 3:9; mean age +/- SD, 36.7 +/- 7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the threshold dose of oral aspirin. RESULTS: In the placebo arm, oral aspirin significantly decreased FEV 1 concomitant with significant increases in sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. Tacrolimus significantly inhibited bronchoconstriction and abrogated aspirin-induced increase in both sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. CONCLUSION: The current study suggested that tacrolimus inhibited bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl leukotriene excretion.     

Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitization in Mongolia

BACKGROUND: Studies in countries, such as Mongolia, which are in transition from farming to industrial society permit evaluation of the impact of environmental change on atopic diseases. METHODS: In the screening study, questionnaire data were obtained from 9453 subjects aged 10-60 years. In the clinical study, a subsample of 869 subjects (participation rate 50.0%) was examined. A questionnaire-based interview, clinical examination, skin prick tests, spirometry and bronchodilation test or methacholine challenge test were used to define the clinical diagnoses. The prevalences of atopic diseases were evaluated at the population level using two-phase data and sampling weights. RESULTS: The prevalences of asthma, allergic rhinoconjunctivitis and allergic sensitization with 95% confidence intervals were 1.1% (0.3-2.0%), 9.3% (4.0-14.6%) and 13.6% (7.4-19.9%) in Mongolian villages, 2.4% (1.4-3.5%), 12.9% (8.2-17.7%) and 25.3% (17.1-33.6%) in rural towns and 2.1% (1.3-3.0%), 18.4% (13.3-23.4%) and 31.0% (24.5-37.5%) in Ulaanbaatar city, respectively. The prevalence of allergic rhinoconjunctivitis (P = 0.02) and allergic sensitization (P = 0.003) increased significantly with increasing urbanization. CONCLUSIONS: The prevalences of atopic diseases were low in rural Mongolia and increased with increasing urbanization suggesting that rural living environment protects against atopy.     

The effect of passive smoking on asthma symptoms,atopy,and airway hyperresponsiveness in schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey.