Fractal Geometry of Airway Remodeling in Human Asthma.

Green FH.

Dalhousie University, Halifax, Nova Scotia, Canada.

Airway wall remodeling is an important aspect of human asthma. In this study fractal analysis was used to provide a relatively simple method for developing a quantitative index of airway wall remodeling in asthmatic and non-asthmatic airways. Negative pressure silicone rubber casts of lungs were made using autopsy material from three groups: fatal asthma, non-fatal asthma and non-asthma control. All subjects were lifelong non-smokers. Non-asthma control casts had smooth walls and dichotomous branching patterns with non-tapering segments. Asthmatic casts showed many abnormalities including airway truncation from mucous plugs, longitudinal ridges and horizontal corrugations corresponding to elastic bundles and smooth muscle hypertrophy, respectively, and surface projections associated with ectatic mucous gland ducts. Fractal dimensions were calculated from digitized images using an information method. The average fractal dimensions of the airways of both the fatal asthma (1.72) and non-fatal asthma (1.76) groups were significantly (p<0.01; p=0.032, respectively) lower than that of the non-asthma control group (1.83). The lower fractal dimension of asthmatic airways correlated with a decreased overall structural complexity and pathologic severity of disease. This is the first study to use fractal analysis to assess the chronic structural changes of airway remodeling in asthma.

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Extended Haplotype in the TNF Gene Cluster is Associated with Asthma and Asthma Related Phenotypes.

Weiss ST.

Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Anesthesia, Children's Hospital and Harvard Medical School, Boston, MA, USA.

Rationale: Tumor necrosis factor (TNF) is a proinflammatory cytokine found in increased concentrations in asthmatic airways. The TNF alpha (TNF) and Lymphotoxin alpha (LTA) genes belong to the TNF gene superfamily located within the human major histocompatibility complex on chromosome 6p in a region repeatedly linked to asthma. The TNF -308 and LTA NcoI polymorphisms are believed to influence TNF transcription and secretion, respectively. Objectives: To determine if polymorphisms in TNF or LTA, or TNF-LTA haplotypes, are associated with asthma and asthma phenotypes. Methods: We genotyped the TNF -308 and LTA NcoI polymorphisms, and two other haplotype tagging polymorphisms in the TNF and LTA genes, in 708 children with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP)and their parents. Using an extension of the family based association tests in the PBAT program, each polymorphism was tested for association with asthma, age of onset of asthma and with time series data on baseline FEV1 % predicted, post-bronchodilator FEV1 % predicted, body mass index, and log of PC20. Measurements and Main Results: Although no associations were found for the individual SNPs, the haplotype analysis found the LTA NcoI_G/LTA 4371T/TNF -308G/TNF 1078G haplotype to be associated with asthma and with all 5 phenotype groups. Conclusions: We conclude that it is unlikely that the TNF -308 or LTA NcoI polymorphisms influence asthma susceptibility individually, but that this haplotype of variants may be functional or may be in linkage disequilibrium with other functional SNPs.

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Gastroesophageal reflux disease in children with asthma : treatment implications.

Canning BJ.

Maryland Institute for Asthma and Allergy, Wheaton, Maryland, USA.

An association between asthma and gastroesophageal reflux disease (GERD) has long been recognized both mechanistically and epidemiologically. The clinical relevance of this interplay continues to be explored, with special interest given to the role of GERD in the worsening of asthma. The effect of GERD is most frequently contemplated in patients with asthma that is difficult to control.Medical and surgical anti-reflux trials attempting to alter asthma symptoms have reported mixed but generally underwhelming results, although asthma symptom scores are generally improved following effective treatment of GERD. Many of the pharmaceutical studies can be criticised for having too short a duration or for likely incomplete acid suppression.Few trials have specifically studied pediatric populations. Because GERD is a common condition, particularly in young children, the role reflux plays in the worsening of asthma symptoms and the potential benefit on asthma of anti-reflux therapy warrants further exploration. Whether or not treating symptomatic GERD reduces the symptoms and severity of asthma in children, GERD coexisting with asthma should be aggressively treated. GERD symptoms in most patients with or without asthma can be controlled medically with continuous use of proton pump inhibitors such as omeprazole and lansoprazole and to a lesser extent by histamine H(2) receptor antagonists such as famotidine and cimetidine.

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Home-based asthma self-management education for inner city children.

Bollinger ME.

Abstract Optimal home self-management in young children with asthma includes accurate symptom identification followed by timely and appropriate treatment. The objective of this study was to evaluate a home-based asthma educational intervention targeting symptom identification for parents of children with asthma. Two hundred twenty-one children with asthma were enrolled into an ongoing home-based clinical trial and randomized into either a standard asthma education (SAE) or a symptom/nebulizer education intervention (SNEI). Data included home visit records and parent's self-report on questionnaires. Symptom identification and self-management skills significantly improved from preintervention to postintervention for parents in both groups with the exception of checking medications for expiration dates and the frequency of cleaning nebulizer device and equipment. However, significantly more parents of children in the SNEI group reported treating cough symptoms as compared with the SAE group (p = 0.05). Of concern is that only 38% of all parents reported having an asthma action plan in the home. A targeted home-based asthma education intervention can be effective for improving symptom identification and appropriate use of medications in children with asthma. Home asthma educational programs should address accurate symptom identification and a demonstration of asthma medication delivery devices.

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Genetics and environmental risk factors associated with asthma in schoolchildren.

Sabbah A.

Department of Medical Statistics and Epidemiology, Hamad Medical Corporation and Hamad General Hospital, PO Box 3050, Doha, State of Qatar. abener hmc.org.qa

OBJECTIVES: The objective of this study was to investigate the genetic and environmental risk factors associated with asthma among Qatari school children aged 6-12 years. DESIGN: A cross-sectional study was performed. The International study of asthma and allergies in childhood (ISAAC) and some additional questionnaires were used to collect the data of the school children between Feb 2003 and Feb 2004. SETTING: Government primary schools in the State of Qatar. SUBJECTS: A multistage sampling design was used and a representative sample of 3500 children were targeted for this study. Of these, 3204 parents (91.6%) of the children agreed to participate in this study. RESULTS: Of the total study sample 3204 school children living in urban and semi urban areas, 51.9% were boys and 48.1% girls. Their mean age was 8.92 +/- 1.89. The population sample had a high prevalence rate of asthma (19.8%) and allergic rhinitis 30.3%. The frequency of asthma, allergic rhinitis and eczema among parents reflected the same pattern as that seen in the children. Environmental risk factors associated with asthma were pets at home, allergic to certain food or medicine, smoking history among parents or elder siblings (p<0.0001). A stepwise logistic regression analysis results showed that allergic to food and medicine, history of asthma in father, mother, siblings and asthma in second degree relatives and smoking habit of father were significant predictors for asthma after adjusting age and sex and other confounding covariates in the model. CONCLUSION: The present study revealed that the family history of asthma contributed more to childhood asthma than indoor and outdoor environmental factors. Boys were found more asthmatic than girls. The results of this study support the hypothesis that asthma is a multi-factorial disease related to both familial and environmental influences.

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Changes in asthma prevalence and impact on health and function in Seattle middle-school children: 1995 vs 2003.

Redding GJ.

Department of Pediatrics, Pulmonary Division, Children's Hospital & Regional Medical Center, University of Washington School of Medicine, Seattle, Washington 98105, USA. edward.carter seattlechildrens.org

BACKGROUND: The prevalence of asthma has increased during the past several decades but may have stabilized during the last 5 years. It is not known whether the functional and health impact of asthma has decreased during the past decade. OBJECTIVE: To evaluate changes during a recent 8-year period in the prevalence and health and functional impact of current asthma symptoms in young teenagers. METHODS: In 1995 and 2003, 2,330 and 2,397 middle-school students from Seattle, WA, respectively (median age, 13 years), completed written surveys and answered questions pertaining to 4 wheezing or asthma video scenarios. Children were categorized as having physician-diagnosed current asthma (wheeze in the past year and a physician diagnosis of asthma), undiagnosed current asthma symptoms (wheeze in the past year without a physician diagnosis), or no asthma. Outcome measures were the prevalence of asthma and undiagnosed asthma symptoms and the differences between years in respiratory-associated functional impairment (exercise limitation, missed school, disrupted sleep) and health impact (physician visits, wheeze-limited speech). RESULTS: The prevalence of physician-diagnosed current asthma increased from 1995 to 2003 (3.0% to 6.2%), whereas that for undiagnosed current asthma symptoms decreased (12.0% to 6.2%). The degree of functional and health impairment was similar between the 2 study periods for each subgroup and was highest in the children with physician-diagnosed current asthma. CONCLUSIONS: The prevalence of current asthma symptoms in middle-school children from Seattle decreased slightly between 1995 and 2003, whereas the diagnosis of asthma increased. However, the health and functional impact of asthma did not diminish. Asthma is being diagnosed more often, but many children with asthma are still not achieving good asthma control.

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Socioeconomic Risk Factors for Asthma in Chilean Young Adults.

Rona RJ.

Emory University.

Objectives: We studied the association between socioeconomic status (SES) and asthma symptoms, severity of asthma, atopy, and bronchial hyperresponsiveness (BHR) to methacholine. Methods: We studied 1232 men and women born between 1974 and 1978 in a semirural area of Chile. We assessed asthma symptoms with a standardized questionnaire, atopy with a skin-prick test to 8 allergens, and BHR to methacholine with the tidal breathing method. SES was derived from several indicators: education, occupation, completion of a welfare form, belongings, housing, number of siblings, and overcrowding. Results: Those with fewer belongings had more asthma symptoms. Those who had higher education and those who owned cars had fewer asthma symptoms and BHR. Overcrowding was negatively related to atopy, atopy with asthma symptoms, and BHR. Higher education and noncompletion of a welfare form were risk factors for atopy. Conclusion: The strength and direction of the association between asthma and SES depended on what definition of asthma was analyzed. Asthma symptoms were more common among poor people. There was some support for the hygiene hypothesis as overcrowding was associated with less wheezing with atopy, less atopy, and less BHR.

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Asthma severity and genetics in Taiwan.

Huang JL.

Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital and Chang Gung University, Taoyuan, Taiwan. E-mail: long adm.cgmh.org.tw.

The prevalence of childhood asthma in Taiwan has increased dramatically during the last 2 to 3 decades. In Taipei city, the prevalence of asthma in schoolchildren has increased from 1.3% in 1974 to 19.0% in 2003. Genetic mapping and candidate gene analyses have revealed suggestive evidence for linkage of asthma to a number of different chromosomal regions and for association with several candidate genes. Over 70 variants in candidate genes have been reported to be associated with these phenotypes. The main regions these variants have been found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma susceptibility genes or complexes have been identified using a positional approach. These are A desintegrin and metalloproteinase 33 (ADAM33), dipeptidyl peptidase 10 (DPP10), plant homeodomain zinc finger protein 11 (PHF11) and SET domain, bifurcated 2, G-protein related receptor for asthma (GPRA) and serine protease inhibitor Kazal type 5 (SPINK5). It is also evident that environmental factors will influence the expression of genes and the ultimate clinical phenotype of asthma and atopy. Evidence for a genetic contribution to risk for fatal or near-fatal asthma in Caucasians and Taiwanese has been suggested. We have revealed that the regulation upon activation, normal T cell expressed and secreted (RANTES)-28C/G polymorphism exacerbates asthma severity and represents a genetic risk factor for life-threatening asthma attacks in Chinese children. Moreover, in the Chinese children the frequency of the chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) 1651G allele in near-fatal asthmatics was significantly higher than in mild-to-moderate asthmatics and normal controls. The CRTH2 1651G allele of single nucleotide polymorphism re545659 was also associated with a higher degree of bronchial hyperresponsiveness.

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