The RANTES promoter polymorphism: a genetic risk factor for near-fatal asthma in Chinese children.

Huang JL.

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, Taiwan, ROC.

BACKGROUND: RANTES promoter polymorphisms were found associated with asthma/atopy in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and different asthma severity. OBJECTIVE: The purpose of this investigation was to test the genetic association between the RANTES -28C/G and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children, with particular emphasis on those patients who had experienced life-threatening asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134 children with mild-to-moderate asthma, 69 children with allergic disorders but no asthma, and 107 nonasthmatic nonatopic control children were genotyped through use of a PCR-based assay. RESULTS: No significant difference was demonstrated for frequency of the RANTES -28C/G polymorphism when the mild-to-moderate asthma, atopic/nonasthmatic, and normal control groups were compared. The RANTES -28G allele was present in a significantly higher proportion of the children with near-fatal asthma compared with the nonasthmatic nonatopic controls (odds ratio, 2.93 [1.41-6.06]; P =.006) and the children with mild-to-moderate asthma (odds ratio, 3.52 [1.73-7.16]; P =.001). The frequency of -28G allele carriage correlated with asthma severity. The RANTES -28G allele was also associated with an increased blood eosinophil count and a higher degree of bronchial hyperresponsiveness. The RANTES -403G/A polymorphism did not influence asthma/atopy susceptibility, blood eosinophil count, or bronchial hyperresponsiveness. Interestingly, a higher frequency of -403A allele carriage was observed in the moderate asthma subgroup compared with the mild asthma analog. CONCLUSIONS: We conclude that the RANTES -28C/G polymorphism exacerbates asthma severity, representing a genetic risk factor for life-threatening asthma attacks in Chinese children. In addition, the linkage disequilibrium between these 2 polymorphisms is a potential confounder that must be considered in the design and interpretation of RANTES gene association studies.

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Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: association with asthma severity, neutrophilic inflammation, and wound repair.

Chu HW.

National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.

BACKGROUND: Asthma likely involves an active injury and repair process, including components such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although MMP-9 is increased in lavage fluid and sputum in patients with asthma, controversy exists as to the role of tissue MMP-9. OBJECTIVE: The purpose of this study was to determine whether increases in submucosal cellular MMP-9, matrix MMP-9 (subepithelial basement membrane [SBM]), or both would be associated with severe asthma, neutrophilic inflammation, and wound repair. METHODS: Immunohistochemical staining and analyses of MMP-9, inflammatory cells, transforming growth factor beta, and collagen I were performed in endobronchial biopsy specimens, bronchoalveolar lavage fluid, or both from 38 patients with severe asthma and compared with results in 10 patients with mild asthma, 8 patients with moderate asthma, and 10 healthy control subjects. RESULTS: A significantly greater proportion of patients with severe asthma demonstrated MMP-9 staining of the SBM than control subjects (P =.02). Bronchoalveolar lavage MMP-9 levels were also increased in patients with severe asthma (P =.0004). The numbers of submucosal neutrophils and macrophages, but not eosinophils, were significantly higher in asthmatic individuals with MMP-9 staining of the SBM (P =.004 and P =.01, respectively). However, the presence of SBM MMP-9 was associated with a high correlation between lavage and tissue eosinophils (r = 0.58, P =.009). Although the SBM thickness did not differ between groups, higher numbers of transforming growth factor beta-positive cells were seen in subjects with SBM MMP-9 staining. Pulmonary function was significantly lower in those asthmatic subjects with SBM staining. CONCLUSIONS: These results suggest that localized tissue MMP-9 might play an important role in wound repair and cell trafficking.

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The health politics of asthma: environmental justice and collective illness experience in the United States.

McCormick S.

Department of Sociology, Brown University, Maxcy Hall Box 1916, Providence, RI 02912, USA. phil_brown brown.edu

While public health, medical, government, and community actors agree that there is a serious asthma epidemic, there is significant disagreement over the role of outdoor environmental factors in causing or triggering asthma. The outcome of these disputes is important because it substantially influences the focus of public health prevention and government regulation. Minority communities in the United States have higher morbidity rates than white communities and, as a result, are more readily affected by debates over environmental factors and subsequent public health and government efforts. Therefore, asthma has figured prominently in community activists' agendas concerning health inequalities. We compare and contrast the efforts of two community environmental justice organizations that include asthma as part of their overall community organizing efforts. We explore obstacles and strategies common to both groups as well as key differences in their orientation vis-a-vis science. To do so, we first discuss the discovery, current research, community action, and resultant changes in the understanding of the disease, specifically within poor and minority communities. Then, to offer a context to examine our two examples of asthma activism, we explore the social discovery of asthma and its environmental correlates, along with the political and economic conflicts surrounding asthma research and regulation. Using examples from the two activist groups, we discuss common approaches to address asthma in poor and minority communities such as challenging "transit racism", employing an environmental justice perspective, and using education to empower community members. Finally, we explore how the issues raised in terms of asthma and the environment lead to a collective form of illness experience, in which people with asthma make direct links to the social determinants of their health.

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Do school-based health centers provide adequate asthma care?

Ozuah P.

Albert Einstein College of Medicine/Children's Hospital, Montefiore, 3444 Kossuth Ave., DTC Bldg., First Floor, Bronx, NY 10467, USA. toruwariye aol.com

School-based health centers (SBHCs) are increasingly charged with providing primary care services including asthma care. This study assessed SBHC provider adherence to the National Heart, Lung, and Blood Institute (NHLBI) asthma care guidelines and the association among provider adherence, patient characteristics, and asthma outcomes. A cross-sectional study design was used to assess SBHC chart data from 415 children with asthma attending four inner-city elementary schools (K-5) in the Bronx, NY. Asthma symptoms, peak flow use, follow-up visits, and referrals to asthma specialists were documented in the charts of 60%, 51%, 22%, and 3% of subjects, respectively. Thirty-three percent of charts had SBHC clinician-documented severity classifications, of which 70% had appropriate medications prescribed. Asthma education and an asthma plan were documented in 18% and 10% of charts, respectively. Environmental triggers and tobacco exposures were documented in 71% and 49% of charts, respectively. Older children (> 8 years) were more likely to have documentation of peak flow use for asthma management, asthma education, follow-up visits, and written asthma plans, whereas younger children (< 8 years) were more likely to miss more days of school (all p < .05). Overall, provider adherence to NHLBI guidelines was inadequate, with adherence somewhat better for older children.

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Prevalence of bronchial asthma among bank employees of Vellore using questionnaire-based data.

Cherian AM.

Department of Pulmonary Medicine, Christian Medical College, Vellore 632004.

Asthma and related allergic disorders are reported to be rare in poor and developing countries and their prevalence is expected to rise with urbanisation. Investigation was carried to see the prevalence of asthma and asthma-related symptoms by using a simple questionnaire-based data collection. One hundred and twenty bank employees were studied in the age group 25-55 years in 4 centres of Vellore town. A one-page questionnaire in English regarding asthma and allergic symptoms was used to assess the prevalence and the details of medical care utilisation by those who were asthmatics. The prevalence of self-reported bronchial asthma was 8.3% and that of asthma-related symptoms 15.8%. A significant number of subjects with symptoms suggestive of asthma self-reported themselves as non-asthmatic. There was a significant association between those who had symptoms of asthma and a positive family history of asthma. Most of the asthmatic subjects using allopathic medicines reported a poor quality of life, despite treatment. The prevalence of asthma in Vellore town is more than that reported in other studies carried out at different centres in India. The prevalence may actually be higher since a significant number of subjects with symptoms suggestive of asthma reported themselves as non-asthmatic subjects. As expected, positive family history was forthcoming in subjects with asthma symptoms. Most asthmatic subjects have not experienced a significant improvement in their quality of life, which could indicate sub-optimal management. These findings can form the basis for further studies to investigate factors that lead to these variations.

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Relationships of allergic sensitization, total immunoglobulin E and blood eosinophils to asthma severity in children of the EGEA Study.

Pin I.

Departement de Medecine Aigue Specialisee, CHU Grenoble, France. vsiroux chu-grenoble.fr

BACKGROUND: Although allergy is highly associated with childhood asthma, it is not well known if there is a relationship between the intensity of allergic sensitization and asthma severity. OBJECTIVE: The objectives of the study were to examine the relationships between several markers of allergy and asthma severity in asthmatic children included in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA). METHODS: The population comprised 216 asthmatic children below 16 years of age. Total IgE and blood eosinophil counts were measured and skin prick tests to 11 aeroallergens were performed. The intensity of the allergic sensitization was assessed by the number of positive skin prick tests and by skin weal sizes. Asthma severity was measured with four criteria: a clinical severity score, history of hospitalization for asthma, FEV1% predicted and inhaled steroid use in the last 12 months. RESULTS: Most of the children were sensitized to at least one aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for a tendency for a more severe clinical score in non-atopic children. The type and intensity of the allergic sensitization were not associated with any criteria of asthma severity. Total IgE was significantly increased in children treated with inhaled corticosteroids and in children ever hospitalized for asthma (P-values 0.009 and 0.04, respectively). Eosinophil counts were not related to asthma severity. CONCLUSION: Our results suggest that severe childhood asthma may be related to a high level of total IgE but not to blood eosinophil counts. The lack of positive relationships between both atopy and the intensity of allergic sensitization with asthma severity supports the hypothesis of different risk factors being associated with asthma and with the severity of asthma.

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Roles of genotypes of beta2-adrenergic receptor in the relationship between eosinophil counts and lung function in Taiwanese adolescents.

Su HJ.

Graduate Institute of Environmental and Occupational Health, National Cheng Kung University, College of Medicine, Tainan, Taiwan.

To examine the roles of genetic polymorphism of the beta2-adrenergic receptor (beta2AR) in the relationship between eosinophil (EOS) counts and eosinophil cationic protein (ECP) counts and lung function, we recruited a random sample from the 1996 nationwide survey of asthma prevalence in middle school children. A total of 149 subjects--42 asthmatic children, 38 asthmatics in remission (no reported attack for more than 12 months), and 69 nonasthmatics--completed a physical evaluation, pulmonary function test, and determination of EOS, ECP, and beta2AR genotypes at amino acids 16 and 27. Asthmatic children had higher EOS and ECP than did nonasthmatics. No association was found between asthma and beta2AR genotypes. Lung function was significantly and inversely correlated with EOS but not with ECP in asthmatic children. By genotype, an inverse correlation between lung function and EOS was found in asthmatic children with Arg16Arg or Gln27Glu. A nonsignificant but similar inverse correlation was found in asthmatic children with Arg16Gly or Gln27Gln. However, a nonsignificant but positive correlation was found in asthmatic children with Gly16Gly. In conclusion, we suggest that EOS is a better clinical indicator of airway inflammation than ECP when children are not having an asthma attack. The association between an increase of EOS and lower lung function can be differentiated by beta2AR genotypes at amino acid 16.

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Medication adherence in pediatric asthma: reasoning, responsibility, and behavior.

Fritz GK.

Child Psychiatry, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903, USA. emcquaid lifespan.org

OBJECTIVE: To assess child adherence to preventive asthma medications; to investigate relations between knowledge, reasoning about asthma, and responsibility for management and adherence; and to determine the association between adherence and morbidity. METHODS: Participants were 106 children with asthma and their parents. Medication adherence was electronically monitored for 1 month. Participants completed self-report measures. Children were interviewed to assess reasoning about asthma. RESULTS: Children's adherence was approximately 48% of prescribed doses. Adherence was negatively related to age (r = -.21, p <.05); minority status, F(1, 98) = 7.55, p <.01; and morbidity (r = -.26, p <.01). Age was associated with increased child knowledge (r =.47, p <.001), reasoning about asthma (tau =.23, p <.01), and responsibility for asthma management (r =.44, p <.01). These variables were not associated with adherence. CONCLUSIONS: Although older children know more about asthma and assume more responsibility for disease management, their adherence is lower than that of younger children. No association was found between adherence and child knowledge, reasoning about asthma, or responsibility for asthma management.

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