Structural changes of the airway wall impair respiratory function, even in mild asthma.

Adachi M.

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.

STUDY OBJECTIVES: To clarify whether structural changes of the airway wall impair respiratory function in patients with mild asthma, and to determine whether mild asthma should be treated with inhaled steroids. SETTING: Showa University Hospital in Tokyo. PATIENTS: Thirteen healthy nonatopic volunteers (control subjects), 26 patients with mild asthma treated with a bronchodilator alone without oral or inhaled corticosteroids or antiallergic agents, and 10 patients with mild-to-moderate asthma treated with inhaled corticosteroids. MEASUREMENTS: We measured the thickness of the epithelial reticular basement membrane (Rbm) of the airway wall in bronchial biopsy specimens from patients with asthma and from healthy control subjects. We also performed spirometry and histamine challenge tests to evaluate airflow obstruction and airway hyperresponsiveness. RESULTS: The thickness of the Rbm in patients with mild asthma was significantly greater than that in healthy control subjects and was negatively correlated with the FEV(1) as a percentage of FVC and the provocative concentration of histamine that caused a 20% decrease in FEV(1) from the post-saline solution baseline value. Moreover, the Rbm was thicker in patients with mild asthma not treated with inhaled steroids than in patients with mild-to-moderate asthma treated with inhaled steroids. CONCLUSIONS: The thickness of the Rbm is increased even in mild asthma and is correlated with airway obstruction and hyperresponsiveness. Our results suggests that anti-inflammatory treatment with inhaled steroids should be started in the early stage of bronchial asthma to prevent structural changes from occurring in the airway wall.

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Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma.

Sepper R.

Institute of Experimental and Clinical Medicine, Tallinn, Estonia. kaiu.prikk helsinki.fi

Matrix metalloproteinases (MMPs) contribute to extracellular matrix and basement membrane degradation in asthma. The present study analyzed molecular forms and degree of activation and expression of MMP-8 in bronchoalveolar lavage fluid (BALF), BALF cells, and bronchial tissue specimens from 14 steroid-naive asthma patients, 13 uncontrolled severe asthma patients, 13 controlled asthma patients, and 14 healthy subjects by Western immunoblotting, immunohistochemistry, and in situ hybridization. Immunohistochemistry and in situ hybridization revealed a prominent MMP-8 immunoreactivity in submucosal inflammatory, glandular, and shed, but not in intact bronchial epithelial cells of asthma patients. In BALF cytospins, both MMP-8 protein and mRNA expression were observed in epithelial cells, macrophages, and polymorphonuclear leukocytes (PMNs). MMP-8 was present in BALFs asthma patients in complex, pro- and active PMN-type, and pro- and active non-PMN-type forms. BALF MMP-8 was significantly converted to active form only in BALFs from steroid-naive and uncontrolled severe asthma patients, but not in BALFs from well-controlled asthma patients or healthy controls. A significant inverse correlation between BALF MMP-8 levels and FEV1 (r = -0.283, p = 0.04), and BALF activated MMP-8 forms and FEV1 (r = -0.427, p = 0.001) was detected. Overall, these data suggest that MMP-8 and its activation has an important role in the airway destruction, healing, remodeling, and treatment response in asthma.

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Epidemiological studies of the very high prevalence of asthma and related symptoms among school children in Costa Rica from 1989 to 1998.

Hanson LA.

Department of Pediatrics and Pneumology, National Children's Hospital, University of Costa Rica, San Jose, Costa Rica. msoto hnn.sa.cr

The aim of our study was to determine the prevalence of asthma and related respiratory symptoms in school children from Costa Rica during the last 10 years, from 1989 to 1998. Using nationally representative samples of school children from Costa Rica during the last 10 years we have performed three studies. Altogether 9,931 children were investigated. The age groups: study I, 5-17 years (n = 2,682), study II, 6-7 years (n = 2,944), 13-14 years (n = 3,200) and study III, 10 years (n = 1,105). The diagnostic criteria for asthma used in these studies was as follows: study I (1989), diagnosis by a doctor in combination with the presence of four kinds of respiratory symptoms; studies II (1995) and III (1998), history of wheeze in the past 12 months. The two latter were part of the International Study of Asthma and Allergies in Childhood (ISAAC). A very high prevalence of a history of wheezing was found in the three studies (46.8%, 42.9%, and 45.1%) as well as a diagnosis of asthma (23.4%, 27.7% and 27.1%). The physician's diagnosis of asthma reported in the first study (23%) increased from 23.1 in study II to 27.7% in study III (p = 0.004). This increment could be a real increase in asthma prevalence, or be due to a better awareness about asthma. In study II the group of 6-7-year-olds had respiratory symptoms significantly more often than 13-14-year-olds (p < 0.001). Boys more often had a history of wheezing (p = 0.001), wheeze during the previous 12 months (p = 0.01) and an asthma diagnosis at the age of 6-7 years (p = 0.002) than girls, but girls had more respiratory symptoms than boys at the age of 13-14 years (p < 0.005). Wheezing in the past 12 months was more common for those living in urban areas aged 6-7 years (p = 0.04), and there was an increase of wheeze after exercise (p = 0.01). For the 13-14-year-olds the risk of wheezing was higher during the previous 12 months if they lived in temperate areas (<20 degrees C) and at a high altitude (>1,000 m). Living in a rural area and in a warm region (>20 degrees C), increased the risk of dry cough during the previous 12 months in the group of 13-14-year-olds. In conclusion, Costa Rica is located in the tropics with a very high humidity, an enormous variety of flora and fauna and a very high prevalence of mite and cockroach allergens, which provide important risk factors that may explain the high prevalence of asthma and asthma-related symptoms. Further possible factors, such as the change towards a more Western life style, resulting in fewer infections and parasitic diseases in the first years of life and changes in bedding material, may also be unresolved. Increased environmental pollution may add to the very high prevalence of asthma and related respiratory symptoms. The very extensive exposure to mites and cockroaches in bed material and in homes with poor ventilation may be an important factor, but many asthmatic children behave as non atopic, with a viral respiratory infection as a major precipitating factor.

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Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program.

Weiss ST.

Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Interleukin 13 (IL-13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case-control genetic-association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506-513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549-559). To apply family-based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty-six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL-13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT-GEE, a multivariate extension of the family-based association test (Lange et al. [2002] Biostatistics 1:1-15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity. Copyright 2002 Wiley-Liss, Inc.

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Self-reported asthma in adults and proxy-reported asthma in children--Washington, 1997-1998.

.

Increased awareness of asthma as a public health problem reflects recent increases in asthma prevalence, asthma-related visits to hospital emergency departments, and asthma-related mortality. To assess the prevalence of asthma in Washington, the Washington State Department of Health added survey items on asthma to its 1997 and 1998 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report summarizes the results of those surveys, which indicate that persons with asthma reported significantly lower health status than other respondents and that a substantial proportion of households with children reported having a child with asthma.

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Atopy, passive smoking, respiratory infections and asthma among children from kindergarten and elementary school.

Jardim JR.

Departamento de Medicina Preventiva, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil. sandrarib medprev.epm.br

CONTEXT: It has been demonstrated that children exposed to parents who smoke have more respiratory infections and asthma. OBJECTIVE: To study the association of both respiratory infections and asthma attacks with atopy, passive smoking and time spent daily at school, among children aged 4 to 9 years old from a kindergarten and elementary school in the city of Sao Paulo between May and July of 1996. TYPE OF STUDY: Descriptive study. SETTING: A kindergarten and elementary school with linkages to Universidade Federal de Sao Paulo/Escola Paulista de Medicina. PARTICIPANTS: 183 children between 4 and 9 years old. MAIN MEASUREMENTS: A questionnaire consisting of 31 questions was answered by the parents of 183 children, and skin tests for inhaled antigens were performed on 88 children whose parents had given prior agreement for the procedure. RESULTS: Among the children, 51% had had respiratory infections during the preceding 3 months and 25.7% were asthmatic, of whom 52.1% had had one or more asthma attacks during the preceding 3 months. Children exposed to passive smoking did not have more respiratory infections or asthma attacks in comparison with those not exposed. We observed a significant association between atopic disorders in parents and children who were not exposed to passive smoking. There were also associations between atopic disorders in parents and asthma attacks in their infants, and between such disorders and a higher incidence of respiratory infections in the infants during the preceding 3 months. However, the presence of two or more positive skin tests for allergies did not have a correlation with respiratory infections and asthma attacks in this sample. In addition to this, children who studied full time at school did not have a higher occurrence of respiratory infections and asthma attacks. CONCLUSIONS: The presence of respiratory infections and asthma was associated with atopic parents but not with the presence of two or more positive skin tests for allergies among the children. Also, respiratory infections and asthma attacks were not associated with smoking parents or with the length of time spent by the children at school.

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Preventive and therapeutic effects of oral tolerance in a murine model of asthma.

Kang CY.

Laboratory of Immunology, College of Pharmacy, Seoul National University, Korea.

Allergic asthma is an inflammatory disease of the airways, and Th2 cells secreting IL-4 and IL-5 play a pivotal role in its pathogenesis. We have previously demonstrated that oral tolerance can be induced and maintained more profoundly in a Th2-related immune response, and that an ongoing immune response can be suppressed by the oral administration of antigen combined with an appropriate feeding regimen. In the present study, we examined the preventive and therapeutic effects of the oral administration of allergen on a Th2-mediated immune disorder using a murine model of asthma. Our results show that the development of asthma can be blocked completely by orally administering allergen. Airway hyperreactivity, allergen-specific IgE production, Th2-derived cytokines, allergen-induced T cell proliferation and the infiltration of inflammatory effector cells into the lung were prevented by such oral administration. To assess the therapeutic effects of oral administration on the progression of asthma, we tested the effects of oral tolerance in an established asthma model, and found that a multiple high dose-feeding regimen was effective at suppressing the progression of mild asthma. In the high dose-feeding group, the number of eosinophils in bronchoalveolar lavage fluid was reduced and airway reactivity also decreased. However, this was insufficient to reduce airway reactivity and eosinophilia in bronchoalveolar lavage fluid in cases of severe asthma. These results demonstrate that allergic asthma may be ameliorated by feeding allergen; there is hope that these results will provide a new immunotherapeutic strategy for allergic asthma.

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Asthma in adventure travelers: a prospective study evaluating the occurrence and risk factors for acute exacerbations.

Giladi M.

Unit of Infectious Diseases and Travel Advisory Clinic, Tel Aviv Sourasky Medical Center, Israel. ygolan lifespan.org

BACKGROUND: Exacerbation of asthma during travel to remote regions may lead to devastating consequences. The course of asthma in travelers and the risk factors for disease exacerbation during travel have not been studied. METHODS: We screened 5835 consecutive travelers and identified 203 patients with asthma. Before travel, all enrollees were assessed for presumed risk factors for asthma exacerbation by means of an interview and an exercise test combined with spirometry. After travel, data regarding travel characteristics and asthma severity were recorded by means of a structured telephone interview. RESULTS: The 203 enrollees visited 56 countries for a median duration of 13 weeks, 147 were engaged in high-altitude trekking, and 88 had asthma attacks. Among these, 40 reported worsening asthma during travel, 32 experienced the worst asthma attack ever, and 11 reported a life-threatening asthma attack. Two independent risk factors for attacks during travel were identified: frequent use (> or = 3 times weekly) of inhaled bronchodilators before travel (relative risk [RR], 3.35; 95% confidence interval [CI], 1.75-6.39) and participation in intensive physical exertion during treks (RR, 2.04; 95% CI, 1.04-3.98). When both risk factors were present, the RR for asthma attacks increased to 5.52 (95% CI, 2.81-10.84). CONCLUSIONS: Asthma frequently worsens during travel and should not be ignored as a potentially life-threatening condition requiring pretravel consideration. Asthmatic travelers who frequently use inhaled bronchodilators before travel or participate in intensive trekking during travel are at increased risk to develop asthma attacks. Therapy should be intensified to achieve better disease control; intensive trekking should be discouraged.

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