Long-term mortality among adults with or without asthma in the PAARC study.

Tessier JF.

Laboratory of Occupational and Environmental Health, Victor Segalen Bordeaux 2 University, Bordeaux, France. stephanie.vandentorren isped.u-bordeaux2.fr

The Pollution Atmospherique et Affections Respiratoires Chroniques (PAARC; Air Pollution and Chronic Respiratory Diseases) study provided the opportunity to examine the 25-yr mortality of 940 asthmatic adults drawn from a large population-based sample of 14,267 adults investigated during 1974-1976 in seven French cities. Vital statistics were collected in 2001 for the whole population. Multivariate survival analysis was used to assess exact survival rates in asthmatics and nonasthmatics taking relevant confounders into account. On average, the mortality rates obtained were 10.4 and 6.9 deaths 1,000 person-yrs-in asthmatics and nonasthmatics, respectively. On univariate analysis, asthma increased the relative risk (RR) of death by 1.48 (95% confidence interval (CI) 1.29-1.69). The association between asthma and death had an RR of 1.16 (95% CI 0.99-1.37) when age, sex, educational level, smoking habits, occupational exposure and forced expiratory volume in one second (FEV1) were taken into account. FEV1 was an important contributive factor causing increased risk of death in both smokers and nonsmokers. For instance, in asthmatics, the numbers of deaths due to respiratory disease and cancer appeared excessive. The present study suggests that asthmatics exhibit a higher risk of mortality.

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Long-term changes in adult asthma prevalence.

Gulsvik A.

Dept of Thoracic Medicine, Institute of Medicine, University of Bergen, Norway. jan.brogger med.uib.no

There has been an increase in asthma prevalence among children. Little evidence is available regarding long-term changes in asthma prevalence in adults. Two cross-sectional studies were performed among adults aged 15-70 yrs in Oslo, Norway, in 1972 and again in 1998-1999 (n=39,998). A postal self-completed questionnaire was used. Exactly the same questions and survey methods were used in both studies. In 1998-1999, additional telephone follow-up was included for postal nonresponders. The crude prevalence of ever having had a doctor's diagnosis of asthma increased from 3.4 to 9.3%. The prevalence of wheezing increased from 17.8 to 25.8% and attacks of breathlessness from 12.6 to 16.7%. After controlling for smoking, the risk of asthma among those aged <40 yrs had tripled. The increase in asthma was 50% greater in females than males. The prevalence of symptoms increased less than asthma diagnosis. Wheezing increased by 50% in those aged <40 yrs, with smaller increases at greater ages. The increase in symptoms was seen among both asthmatics and nonasthmatics. There has been a large increase in the prevalence of asthma diagnosis and asthma-like symptoms in adults. The increase is less pronounced among those aged >40 yrs.

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Association of psychiatric disorders and different indicators of asthma in island Puerto Rican children.

Klein RB.

Yale University, Department of Epidemiology and Public Health, Division of Health Policy and Administration, 60 College Street, P. O. Box 208034, New Haven, CT 06520-8034, USA. alexander.ortega yale.edu

BACKGROUND: We examined the relationship between three different indicators of childhood asthma (asthma diagnosis, ever had an asthma attack, and asthma hospitalization) and having any psychiatric disorder, comorbid disorders, or specific disorders. Three study hypotheses were examined: 1) there will be subject variability in responses to the asthma indicators; 2) there will be different observed associations between the three asthma indicators and psychiatric disorders; and 3) maternal mental health, family income, and maternal education will confound the associations between childhood asthma and psychiatric disorders. METHOD: Data were drawn from a community-based, random sample of 1,891 island Puerto Rican children aged 4-17 years. Information was collected through direct interview with children and adolescents and their primary caretakers. The Diagnostic Interview Schedule for Children (DISC) was used to determine DSM-IV diagnoses. RESULTS: Thirty-two percent of the children had been diagnosed with asthma but only 22 % had ever experienced an asthma attack. Seventeen percent of the children had been hospitalized for asthma. Having been hospitalized for asthma was not associated with any of the psychiatric disorders, having a diagnosis was associated with some of the disorders, and having experienced an asthma attack was associated with almost all the disorders, after controlling for family income and maternal education and mental health. CONCLUSIONS: Determining and measuring asthma may be difficult because of confusion and differing perceptions of what constitutes asthma or an asthma attack. Future studies should consider the problems in capturing perceptions of asthma and severity in Puerto Rican children and should continue to explore the relationship between asthma and mental illness.

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Glutathione peroxidase activity and serum selenium concentration in intrinsic asthmatic patients.

Shirdel H.

Department of Biochemistry and Biophysics, Babol University of Medical Sciences, Babol, Iran. dqujeq hotmail.com

Serum glutathione peroxidase (GSH-Px) activity and selenium concentration were compared in intrinsic asthmatic patients and non-asthmatic control subjects. Serum GSH-Px activity and selenium concentration were assessed in 46 asthmatic patients and 75 age- and sex-matched non-asthmatic subjects by spectrophotometric assay. Mean serum GSH-Px activity was lower in intrinsic asthmatic subjects (9.4 +/- 2.6 pmol NADPH oxidized/min/g of protein) than in non-asthmatic subjects (16.3 +/- 2.9 pmol NADPH oxidized/min/g of protein). Mean serum selenium was lower in intrinsic asthmatic subjects (1.15 +/- 0.23 microM) than in non-asthmatic subjects (1.98 +/- 0.27 microM). Asthmatic patients have significantly lower concentration of selenium and GSH-Px activity measured in serum.

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T cell cytokine profiles in childhood asthma.

Ennis M.

Department of Clinical Biochemistry, Queen's University Belfast, Belfast, UK.

BACKGROUND: An imbalance of T cell subsets in asthma with a predominance of Th2 type cells has been proposed. The aim of this study was simultaneously to detect surface markers and intracellular production of cytokines in T cells from the airways of children with and without asthma. METHODS: Bronchoalveolar lavage (BAL) fluid was obtained by wedging a suction catheter into the distal airway immediately before elective surgery. Cells were stimulated with phorbol 12-myristrate 13-acetate (PMA) and ionomycin and intracytoplasmic cytokine retention was achieved using monensin. The cells were stained with the relevant antibodies and analysed by flow cytometry. RESULTS: No statistical difference was observed between children with atopic asthma, atopic non-asthmatic subjects, and normal controls in the percentage of CD3+ cells producing interleukin (IL)-2 or IL-4. Interferon (IFN)gamma+ T cells were, however, present in a much higher percentage than either IL-2 or IL-4 positive cells. The percentage of IFNgamma+ T cells was significantly increased in subjects with atopic asthma (median 71.3%, interquartile range (IQR) 65.1-82.2, n=13) compared with both atopic non-asthmatic subjects (51.9%, IQR 37.2-70.3, n=12), p<0.05 and normal controls (58.1%, IQR 36.1-66.1, n=23), p<0.01. CONCLUSIONS: These findings indicate that IFNgamma producing T cells are more abundant in the airways of children with atopic asthma than in atopic non-asthmatic subjects and controls. The proinflammatory activities of IFNgamma may play an important role in the pathogenesis of childhood asthma and may suggest that asthma is not simply a Th2 driven response.

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Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating immunoglobulin E in adult asthma.

Hurme M.

Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland. jussi.karjalainen uta.fi

BACKGROUND: IL-10 has several functional effects relevant to asthma. It can modulate IgE production and induce apoptosis in eosinophils. Polymorphisms of IL-10 gene have been shown to affect IL-10 production. OBJECTIVE: To establish whether IL-10 polymorphisms are associated with asthma and phenotype-related characteristics. METHODS: The frequency of three single base exchange polymorphisms (at positions - 1082, - 819 and - 592) and corresponding haplotypes of the IL-10 gene were analysed in 245 adult asthmatic subjects and 405 controls using PCR and restriction fragment length polymorphism (RFLP). The data were assessed for correlations with the eosinophil count, serum IgE and lung function. RESULTS: The IL-10 haplotype frequencies were similar in asthmatics and controls. Eosinophil count median was 2.0- to 3.2-fold higher among asthmatics with rare ATA/ATA genotype than in asthmatics with other genotypes. No such difference was seen in the control group. When analysed by IL-10 haplotype carrier state and gender, male asthmatics with ATA haplotype had 2.8-fold higher serum IgE than those without ATA. A converse association was found in male controls with ATA haplotype, who had 1.9-fold lower serum IgE than their ATA-negative counterparts. The high IL-10-producing GCC haplotype was associated with impaired lung function in smoking male controls while in asthmatics no clear effect on lung function was found with any of the haplotypes studied. CONCLUSION: These results suggest that the eosinophil counts and serum IgE are differently regulated by IL-10 genotype in asthmatic and in normal subjects. However, IL-10 polymorphism is not related to susceptibility in asthma.

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Metalloproteinase-9 is increased after toluene diisocyanate exposure in the induced sputum from patients with toluene diisocyanate-induced asthma.

Nahm DH.

Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea. hspark madang.ajou.ac.kr

BACKGROUND AND OBJECTIVE: Persistent asthma symptoms are associated with airway inflammation and remodeling, which may be mediated through metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP). The aim of this study was to evaluate MMPs and TIMP involvement in toluene diisocyanate (TDI)-induced asthma. MATERIALS AND METHOD: Induced sputum was collected in eight newly diagnosed TDI-induced asthma subjects (group I) before and 7 h after the TDI and placebo challenges and in 12 subjects with TDI-induced occupational asthma diagnosed 5 years previously with persistent asthma symptoms (group II). Sera was collected in group I at diagnosis, and in group II, they were collected at the time of the study. 12 nonasthmatic healthy subjects were enrolled as controls. MMP-9, MMP-2 and TIMP-1 levels in both sputum and serum were measured by enzyme-linked immunosorbent assay (ELISA). Gelatinase activity in the sputum was confirmed by zymographic analysis. RESULTS: The serum TIMP-1 level was significantly higher in asthma patients than in healthy controls (P = 0.01), while MMP-9 level was significantly lower in asthmatic patients (P = 0.03). There was no significant difference in MMP-2 level (P = 0.27). MMP-9 level in the sputum was significantly increased after the TDI challenges (P = 0.01). TIMP-1 level in sputum tended to increase after TDI challenges, but no statistical significance was noted (P = 0.09). MMP-9 and MMP-9/TIMP-1 levels in the sputum were significantly higher in group II than in group I (P = 0.04, P = 0.02) with no significant difference in TIMP-1 level. Minimal amount of MMP-2 was found in sputum. Zymography demonstrated that MMP-9 level increased and active form of MMP-9 was generated after the TDI bronchoprovocation test. CONCLUSION: TDI exposure leads to overproduction of MMP-9, which may induce airway inflammation and remodeling, and then contribute to persistent asthmatic symptoms in TDI-induced asthma.

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[Measurement of the parameters of dose-response curve obtained after the methacholine challenge test]

[Article in Chinese]

Zeng J.

Department of Internal Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041, China.

OBJECTIVE: To investigate the clinical value in the measurement of parameters of the dose-response curve (DRC) obtained after the methacholine challenge test. METHODS: Twenty-seven cases of cough variant asthma (CVA), 29 of mild asthma, 19 of moderate asthma, and 15 healthy volunteers underwent the methacholine challenge test. The dose-response curves were constructed. The following parameters were calculated: position (PC35sGaw), dose-response curve (DRS), ratio of the area under the curve to the logarithm of the maximal concentration (AUC/lg[Cmax]) and maximal response. RESULTS: A plateau appeared in 11 cases among the healthy subjects, while a plateau appeared only in 2 cases of CVA and 2 of asthma. There were no significant differences among the asthmatic groups in the measurements of PC35sGaw and AUC/lg[Cmax] (geometric mean PC35sGaw: mild asthmatics = 0.369, moderate asthmatics = 0.251, cough variant asthmatics = 0.547), AUC/lg[Cmax] was significantly greater in the asthmatic groups than in the normal group [AUC/lg [Cmax](mean +/- s): mild asthmatics = 24.7 +/- 4.7, moderate asthmatics = 26.6 +/- 4.3, cough variant asthmatics = 25.6 +/- 3.7, normal subjects = 15.5 +/- 4.3, P < 0.01]. DRS of moderate asthmatics was significantly greater as compared with cough variant asthmatics (geometric mean DRS: mild asthmatics = 30.761, moderate asthma-tics = 59.020, cough variant asthmatics = 19.231, P < 0.05), but there was no difference between the other groups. PC35sGaw was negatively correlated with DRS (r = 0.866, P < 0.001) and with AUC/lg[Cmax] (r = 0.502, P < 0.001). CONCLUSION: Four parameters of DRC obtained after the methacholine challenge represent airway sensitivity and reactivity respectively. The parameters of DRC of asthmatic patients are different from those of normal subjects. The sensitivity is related to the reactivity, but they are not completely parallel with each other.

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