Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts.

BACKGROUND: The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort-specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016). METHODS: Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6-8 years in six cohorts and 10-12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500-m buffer around the home address at the time of health assessment. Cohort-specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random-effects meta-analysis. RESULTS: Greenness in a 500-m buffer was positively associated with allergic rhinitis at 6-8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta-analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6-8 years and both outcomes at 10-12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups. CONCLUSION: Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.

Combined exposure to dog and indoor pollution: incident asthma in a high-risk birth cohort.

The impact of single exposures on asthma development is better understood than the effect of multiple exposures. The objective of the present study was to evaluate the effect of combined early exposure to dog allergen (Can-f1) plus indoor nitrogen dioxide (NO2) or environmental tobacco smoke (ETS) on asthma and bronchial hyperreactivity (BHR) in a high-risk birth cohort. We also aimed to assess atopy's impact on the effects of these exposures. Peri-birth ETS exposure was measured using cord blood cotinine (CCot). During year 1, atopy, NO2, Can-f1, and urinary cotinine (UCot) were measured. At 7 yrs of age, 380 children were assessed for asthma and BHR. Exposure effects were determined using stepwise multiple linear regression. Co-exposure to elevated Can-f1 and NO2, or Can-f1 and ETS (CCot), increased risk for asthma, relative to having neither such exposure (OR 4.8 (95% CI 1.1-21.5) and 2.7 (1.1-7.1), respectively); similar risks resulted when substituting dog ownership for allergen. Atopy increased asthma and BHR risk associated with several exposures; notably, atopy with elevated UCot, relative to atopy without such exposure, increased risk of BHR (OR 3.1 (95% CI 1.1-8.6)). In a high-risk birth cohort, early co-exposure to Can-f1 and NO2 or ETS increased the risk of incident asthma. Atopy increased the risk of asthma and BHR associated with ETS.

Geographical variations in the prevalence of atopic sensitization in six study sites across Canada.

BACKGROUND: Geographical variations in atopic sensitization in Canada have not been described previously. This study used the standardized protocol of the European Community Respiratory Health Survey-1 (ECRHS-1) to investigate the distribution and predictors of atopic sensitization in six sites across Canada and to compare the results with some ECRHS-1 centers. METHODS: Adults aged 20-44 years in six study sites across Canada underwent allergy skin testing using 14 allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) cat, cockroach, grasses (Timothy grass, Kentucky grass), molds (Cladosporium herbarium, Alternaria alternata, Aspergillus fumigatus, Penicillium), trees (tree mix, birch, Olea europea), and common ragweed. RESULTS: The overall prevalence of atopy (skin test over 0 mm to any allergen) was 62.7%. There was significant geographical variation in the prevalence of atopy in the six study sites (lowest 55.6% [95% C.I.51.3-59.9] in Prince Edward Island, highest 66.0 [61.7-70.3] in Montreal) and of sensitization to each of the allergens tested even after adjustment for confounders. When the first eight of the nine allergens in the ECRHS were used to estimate the prevalence of atopic sensitization, the prevalence of atopy in Canada was 57% compared with 35.2% overall for centers in the ECRHS. The prevalence of atopy in Vancouver (57% [52.3-61.8]) was close to that of Portland, Oregon (52.1% [46.2-58.0]). CONCLUSION: There was a significant variation in atopic sensitization among different study sites across Canada. The prevalence of atopic sensitization is relatively high in Canada compared with sites in the ECRHS and this may, in part, account for the high prevalence of asthma and asthma symptoms in Canada.

A novel study design to investigate the early-life origins of asthma in children (SAGE study).

This is a description of the Study of Asthma, Genes and the Environment (SAGE), a novel birth cohort created from provincial healthcare administrative records. It is a general population-based cohort, composed of children at high and low risk for asthma, living in urban and rural environments in Manitoba, Canada. The SAGE study captures the complete longitudinal healthcare records of children born in 1995 and contains detailed information on early-life exposures, such as antibiotic utilization and immunization, in relationship to the development of asthma. Nested within the birth cohort is a case-control study, which was created to collect information on home environmental exposures from detailed surveys and home dust sampling, to confirm asthma status in children and use this data to validate healthcare database measures of asthma, to determine differences in immune system responsiveness to innate and adaptive immune stimuli in asthma, to genotype children for genes likely associated with the development of asthma and to study the epigenetic regulation of pre-established protective vs allergic immune responses. The SAGE study is a multidisciplinary collaboration of researchers from pediatric allergy, population health, immunology, and genetic and environmental epidemiology. As such, it serves as a fertile, interdisciplinary training ground for graduate students, and postdoctoral and clinician fellows.

Polymorphisms of glutathione S-transferase genes and functional activity in smokers with or without COPD.

OBJECTIVE: To determine the role of polymorphisms of genes regulating glutathione S-transferase (GST) and its plasma GST activity in the pathogenesis of chronic obstructive pulmonary disease (COPD). DESIGN: Case-control study. METHODS: One hundred and sixty-three patients with stable COPD from several community or regional hospitals were matched for age and pack-years smoked with the same number of health controls from the general population. Each participant underwent an interview-based respiratory and smoking questionnaire, lung function testing and gave a blood sample. Genotyping was carried out using a polymerase chain reaction-based method for polymorphisms of glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase P 1 (GSTP1) genes. Plasma GST activity was measured using the spectrofluorometric method. RESULTS: There were no significant differences in the distribution of various genotypes of polymorphisms of GSTT1, GSTM1 and GSTP1 between COPD patients and healthy controls. GST activity was significantly higher in patients compared with controls, irrespective of their different genotypes, and was not different between patients with different levels of airflow obstruction. CONCLUSION: Polymorphisms of GSTT1, GSTM1 and GSTP1 genes are unlikely to be involved in the pathogenesis of COPD in Chinese in Hong Kong and Southern China.

Determinants of chronic obstructive pulmonary disease in Chinese patients in Hong Kong.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is rising in many parts of the world. This is a study of risk factors for COPD in Chinese patients in Hong Kong. DESIGN: Case-control study matched by sex and age (+/-5 years). METHODS: A total of 289 consecutive patients with COPD were recruited from out-patient clinics while healthy controls were recruited from two sources: random population and community centres for senior citizens. All patients and controls underwent a questionnaire-based interview and spirometry. RESULTS: The mean ages of COPD patients and controls were 71.1 +/- 9.4 and 67.5 +/- 9.3 years, respectively. The male to female ratio of COPD patients was 5 to 1. Smoking was found to be the most important determinant for COPD, followed by poor education and low body mass index adjusted for confounders. A dose-dependent relationship was found between the risk of COPD and pack-years smoked. Place of birth, exposure to environmental tobacco smoke and a history of asthma and tuberculosis were not associated with increased risk of COPD. CONCLUSION: Despite a progressive reduction in prevalence, smoking remains the most important predictor of COPD in Hong Kong. Greater anti-smoking efforts are warranted.

Management of childhood asthma.

The guidelines for the management of childhood asthma have evolved from recommendations by experts to being evidence-based as a result of better understanding of the pathophysiology of asthma, awareness of the heterogeneity and early onset of childhood asthma and a new approach to the pharmacological management. While there are reasonably good evidence-based guidelines for the treatment of asthma in children aged over 5 years, there is a paucity of data for preschool children for the most appropriate management. Most guidelines include recommendations on diagnosis of asthma in children and pharmacological treatment according to the severity of the asthma. Environmental control is an important cornerstone of care, and allergen avoidance should be recommended for children with asthma who are known to be sensitised to the allergen. Environmental tobacco smoke remains an important trigger for worsening asthma in all children, and their parents must be encouraged to give up the habit. Educating children with asthma and their care givers on the disease and proper treatment is another vital element in the management of asthma. There remains a major problem with ensuring the implementation of guidelines in most countries. A care gap thus exists between best practice and common practice. The impact on asthma morbidity of developing and implementing guidelines requires appropriate study.

Prevalence and trend of self-reported asthma and other allergic disease symptoms in Morocco: ISAAC phase I and III.

BACKGROUND: The prevalence of asthma and other allergic diseases is increasing in many parts of the world. OBJECTIVE: To determine the prevalence of asthma, rhinoconjunctivitis and skin allergy symptoms in Morocco as part of the International Study of Asthma and Allergic Diseases in Children (ISAAC). METHODS: The survey was conducted using the standardised method of ISAAC Phase III in four centres in Morocco-Casablanca, Marrakech, Ben Slimane and Boulmane-with respectively 1777, 1689, 1008 and 1254 13-14-year-old schoolchildren participating. A comparison of the results with ISAAC Phase I was carried out in two centres. RESULTS: The prevalence of self-reported symptoms of wheeze in the last 12 months (6.4-16.2%), nasal symptoms (27.9-52.8%), rhinoconjonctivitis (8.8-28%) and eczema (13.3-20.2%) varied between centres, and were highest in Casablanca, the largest city in Morocco. Significant increases in almost all symptoms were found in the two centres of Casablanca and Marrakech between ISAAC Phase I and Phase III. CONCLUSION: Morocco could be classified as a country with an intermediate burden of asthma (between 10% and 15%) and other allergic disorders. The prevalence of these symptoms has increased in the past 5 years.

Prevalence and determinants of positive tuberculin reactions of residents in old age homes in Hong Kong.

OBJECTIVE: To determine the prevalence of tuberculous infection and the predictors of positive tuberculin reactivity in old age home residents in Hong Kong. DESIGN: Cross-sectional study. METHODS: A questionnaire-interview and review of medical records were carried out, together with measurement of weight and height/arm span and assessment of nutritional status. A one-stage tuberculin skin test (TST) was performed using two units of PPD RT23. An induration > or = 10 mm was considered as positive. RESULTS: Of 3682 residents (71.7% participation, mean age 82 years) who agreed to undergo a TST, 46.3% had a positive reaction. Factors associated with a significantly higher risk of a positive TST included being male, an ex- or current smoker and having a past history of tuberculosis (TB). Factors associated with reduced positive tuberculin reactivity included older age groups (> 70 years), a history of cancer and chronic obstructive pulmonary disease and low body mass index quartiles. CONCLUSION: In old age homes, the high prevalence of latent tuberculous infection is responsible for the high rate of active TB due to reactivation. Early diagnosis and treatment are necessary to prevent transmission of disease in these crowded environments with susceptible individuals.

Socio-demographic and geographic indicators and distribution of tuberculosis in Hong Kong: a spatial analysis.

OBJECTIVE: To determine the socio-demographic and geographic indicators responsible for the distribution and transmission of tuberculosis (TB) in Hong Kong using geographical information system (GIS) technology. MATERIALS AND METHODS: All patients with bacteriologically proven TB over a period of 3 years (May 1999-April 2002) residing within Hong Kong Island were studied. Molecular characterisation of their sputum isolates by IS6110-based restriction fragment length polymorphism (RFLP) technique was performed. Socio-demographic data were derived from the 2001 Hong Kong population census. Geographic coordinates of patients' addresses were linked to the GIS; large street block groups (LSBGs) were the units of analysis. RESULTS: Of 2387 patients with bacteriologically confirmed TB, 2332 had valid addresses distributed in 430 LSBGs in Hong Kong Island. Of the five socio-demographic indicators studied, significant correlations were found between the rate of TB in an LSBG and low educational attainment, elderly population and low-income household, but not population density or unemployment. The five socio-demographic indicators were not different between LSBG with clustered cases and those with unique cases. CONCLUSION: Low educational attainment, old age and poverty were significant determinants of the rate of TB in different parts of Hong Kong, while none of the socio-demographic indicators was related to disease transmission.

Novel technique for isolation of human lung mast cells.

A novel technique for isolation of human lung mast cells is developed. Human lung tissue was enzymatically digested and the cells were partially purified by centrifugation on Percoll density gradient. Cells obtained at the Percoll density of 1.05-1.09 g/ml were then subjected to a cell sorter equipped with a single argon laser beam (FACS 440). Using four criteria as density, granularity, size and autofluorescence, four major cell populations were identified. One of the major populations contained 70-95% mast cells with a mean and SE values of 88 +/- 11% purity, n = 18 as determined by the measurement of total histamine content, light microscopic observation of stained cells with toluidine blue and estrase, and surface-stained IgE fluorescence antibody. Approximately less than 10% mast cells were identified in the three other major cell populations. Mast cells isolated by FACS were found to be intact, viable (approximately equal to 90%) and functionally normal as determined by the release of histamine evoked after stimulation with ionophone A23187, or challenged with anti-human IgE.

Clinical features and natural history of occupational asthma due to western red cedar (Thuja plicata).

After an average follow-up interval of three and a half years (range one to nine years), 125 patients with occupational asthma due to red cedar exposure were re-examined. Fifty patients remained in the same job. All of them continued to have asthmatic attacks requiring regular medication for relief of symptoms. They had worse lung function and ther bronchial reactivity to methacholine increased. Seventy-five patients left the industry; half of them became asymptomatic, whereas the remaining half continued to have recurrent attacks of asthma. Several factors were of prognostic significance. Those with a shorter duration of exposure as well as a shorter duration of symptoms prior to diagnosis and removal from exposure showed improvement. Those who remained symptomatic tended to be older; they had longer duration of exposure and a longer duration of symptoms prior to diagnosis. They tended to have more abnormal results of lung function studied and more marked bronchial hyper-reactivity to methacholine at the time of diagnosis. They also tended to have dual asthmatic reaction rather than late asthmatic reaction to inhalation challenge with red cedar extract. Smoking, race and degree of peripheral blood eosinophilia did not play a role in determining the outcome. Since none of these patients had symptomatic asthma before employment and since they reacted to inhalation challenge of red cedar, it could be assumed that persistent asthma in those who failed to recover is the result of their previous occupational exposure. Early diagnosis and removal from exposure were found to be associated with recovery.

Occupational asthma.

Many toxic compounds found in air emissions may induce bronchoconstriction. In the workplace, workers are exposed to these compounds, often in much higher concentrations. Some of these compounds act as sensitizers. Of these, some compounds induce asthma by producing specific IgE antibodies to the compound or its protein conjugate, while others induce asthma through yet unidentified immunologic mechanisms. Some compounds, when inhaled in high concentrations, act as irritants and produce bronchoconstriction probably by inducing acute airway inflammation. The latter condition is called Reactive Airways Dysfunction Syndrome (RADS) or irritant-induced asthma. Occupational asthma is an excellent model to study the pathogenesis and the natural history of adult onset asthma because the responsible agent can be identified, complete avoidance is possible, and exposure can be measured or estimated.

The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma.

The effect of disodium cromoglycate and Sch 1000 on exercise-induced asthma was studied in nine patients. The exercise stimulus consisted of either treadmill running or jogging; spirometric measurements were made before and at intervals after exercise. In six patients, disodium cromoglycate and Sch 1000 were both effective in preventing exercise-induced asthma. In two patients, Sch 1000 was effective, while disodium cromoglycate gave no protection. In the remaining patient, disodium cromoglycate was more effective than Sch 1000. The findings of this study suggest that the mechanism of exercise-induced asthma may be multifactorial, and the relative importance of each factor may vary in different patients.

Occupational asthma.

This article review recent developments in the study of occupational asthma and implications for the overall understanding of asthma. Occupational asthma is a clinical syndrome caused by many different agents. Contribution of studies of experimental inhalation challenge using occupational agents to the knowledge of asthmatic reactions and their mechanisms is discussed. Investigations in the occupational environment into predisposing factors and persistence or recovery after exposure to an allergic agent or nonspecific irritant are reviewed. Approaches to diagnosing asthma in the occupational environment and to assessing functional impairment and disability are outlined. Directions for future research are identified.

Respiratory abnormalities among grain elevator workers.

Twenty-two grain workers with respiratory symptoms and lung function abnormalities were studied. Our findings suggest that grain dust asthma probably has an allergic basis, even though skin tests and precipitin studies were negative using extracts of grain dust. Hypersensitivity pneumonitis and grain dust fever were not found in any of the subjects. We found that grain dust can cause airflow obstruction in two ways: first by inducing asthma, probably through immunologic mechanisms, and second, by causing industrial chronic bronchitis.