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.

FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese.

BACKGROUND: Forced expiratory volume in 3 seconds (FEV(3)) and 6 seconds (FEV(6)) could complement FEV(1) and forced vital capacity (FVC) for detecting airflow obstruction. OBJECTIVE: To compare FEV(1)/ FEV(6) and FEV(3)/FVC with FEV(1)/FVC in the detection of airflow obstruction. METHOD: Previous lung function data were re-analysed to establish reference values for FEV(3) and FEV(6). Data from a separate cohort of male smokers were used as test set. FEV(1), FEV(3), FEV(6), FVC, FEV(1)/FVC, FEV(1)/ FEV(6) and FEV(3)/FVC were regressed against age, standing height, weight and body mass index, and the mean and 95% confidence intervals for the lower limit of normal (LLN) values for these parameters were determined. RESULTS: The percentage of smokers with airflow obstruction in the test population using FEV(1)/FVC < LLN was 15.0%, while using FEV(1)/ FEV(6) < LLN and FEV(3)/FVC < LLN they were respectively 18.5% and 18.1%. Using FEV(1)/FVC < LLN as reference, the sensitivity and specificity of FEV(1)/ FEV(6) < LLN in identifying airflow obstruction were 82.3% and 92.8%, while those for FEV(3)/FVC < LLN were 78.5% and 92.6%; the positive and negative predictive values were 67% and 96.7% for FEV(1)/ FEV(6) < LLN and 65.3% and 96% for FEV(3)/FVC < LLN. CONCLUSION: FEV(3)/FVC < LLN and FEV(1)/ FEV(6) < LLN are comparable to FEV(1)/FVC < LLN for detecting airflow obstruction. FEV(3)/FVC < LLN could be useful in screening for airflow obstruction, while FEV(1)/ FEV(6) < LLN is useful in detecting airflow limitation in the elderly or in subjects with severe airflow obstruction.

Early detection of central airway lung cancer in smokers with silicosis.

BACKGROUND: Smokers with silicosis are at increased risk of lung cancer. OBJECTIVE: To evaluate the feasibility of using autofluorescence bronchoscopy after sputum examination for early detection of large airway lung cancer and factors associated with the presence of cancerous and pre-cancerous lesions among smokers with silicosis. METHODS: Subjects at the pneumoconiosis clinic were recruited if they fulfilled the following criteria: 1) age ≥40 years, 2) smoking history of ≥20 pack-years and 3) confirmed diagnosis of silicosis. Sputum specimens were collected for cytology/cytometry examination and autofluorescence bronchoscopy was performed in subjects with an abnormal sputum result. RESULTS: A total of 48 subjects were recruited during the study period. The mean age and smoking history were respectively 63 ± 10 years and 51 ± 30 pack-years. Intraepithelial lung cancers and pre-neoplastic lesions (squamous metaplasia or above) were detected in respectively 2 (4.2%) and 14 (29.2%) subjects. The proportions of current smokers (75.0% vs. 40.6%, P = 0.03) and asbestos exposure (37.5% vs. 9.4%, P = 0.04) were significantly higher in subjects with the above lesions compared with those without. CONCLUSIONS: Sputum examination followed by autofluorescence bronchoscopy may be a useful way of identifying cancerous/pre-cancerous lesions among silicotic smokers. Current smoking and asbestos exposure were associated with these lesions.

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.

Authorship affiliations in original articles submitted to the International Journal of Tuberculosis and Lung Disease.

OBJECTIVE: To ascertain whether the first (principal) and last (senior) authors of articles are affiliated to an organisation belonging to the study country in an analysis of high- and upper-middle-income countries, and low- and lower-middle-income countries. DESIGN: Prospective review of all original articles (n = 911) submitted to the International Journal of Tuberculosis and Lung Disease (IJTLD) from June 2006 to May 2008. RESULTS: In 81% of the submitted articles both the first and the last authors were affiliated to the country of the study. Slightly more articles from low (10%) than from lower-middle-income, high- and upper-middle-income countries (all 4%) had neither the first author nor the last author affiliated to the study country. For 17% of articles from low-income countries the senior author was not from the study country. CONCLUSION: Although acceptance of articles for publication in the IJTLD is not dependent on this criterion, we find that a substantial proportion of authors from low- and middle-income countries were listed as principal and senior authors in articles submitted.

Elevated plasma adiponectin levels in patients with chronic obstructive pulmonary disease.

BACKGROUND: Adiponectin is an anti-inflammatory adipokine that may play a role in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVE: To investigate the relationship between adiponectin, interleukin (IL) 6, IL-8 and C-reactive protein (CRP) and COPD by evaluating these biomarkers in ever-smokers with or without the disease. METHOD: Plasma levels of adiponectin, IL-6, IL-8 and CRP were measured using commercially available kits in COPD patients (n = 71), healthy ever-smokers (n = 62) and non-smokers (n = 51). RESULTS: There were significant increases in plasma adiponectin, IL-6 and CRP in COPD patients (median [IQR] 4.39 microg/ml [2.68-6.98], 4.19 pg/ml [<2.40-6.40], 8.75 mg/l [4.26-40.63], respectively) compared to healthy ever-smokers (1.90 microg/ml [0.86-2.86], <2.40 pg/ml [<2.40-2.77], 3.71 mg/l [1.97-10.37 mg/l], respectively, P < 0.001) and non-smokers (1.76 microg/ml [1.34-2.52], <2.40 pg/ml [<2.40-2.78], 3.12 mg/l [2.11-5.71], respectively, P < 0.001). COPD patients had lower plasma IL-8 levels than healthy ever-smokers. Among ever-smokers with or without COPD, plasma adiponectin, IL-6 and CRP levels were inversely correlated with forced expiratory volume in 1 second (% predicted) after adjustment for age, body mass index, smoking status and pack-years. CONCLUSION: Our findings suggest that in COPD patients, adiponectin might be associated with COPD pathogenesis.

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.

Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics.

BACKGROUND: Asthma is a disease associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported. OBJECTIVE: To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults. METHODS: An age- and smoking status-matched case-control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR-RFLP). Plasma GST activity was measured by fluorometric assay. RESULTS: The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34-0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001). CONCLUSION: Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.

Emerging occupational lung infections.

Recent experiences of emerging infections, such as severe acute respiratory syndrome (SARS) and avian influenza (H5N1), have highlighted the risks of serious pulmonary infections from occupational exposures. Occupationally acquired human immunodeficiency virus (HIV) infection could also result in life-threatening, opportunistic lung infections as a result of host immunosuppression. These three occupationally acquired infections are major public health problems that carry with them enormous economic and societal implications. The present review discusses their microbiology, epidemiology and mode of transmission, clinical features, treatment and, more importantly, prevention. Health care workers (HCWs), who are a valuable health care resource especially in the developing nations, are at high risk for acquiring these diseases. Drugs for the treatment of HIV infection are expensive and not widely available in the developing world where they are most needed. As there is no well-recognised effective treatment for SARS and avian influenza, prevention of infection is most important. HCWs should be aware of occupationally acquired infections and know how to protect themselves. Regular training should be provided by all health care institutions on infection control measures and the use of personal protective equipment.

Polymorphisms and functional activity in superoxide dismutase and catalase genes in smokers with COPD.

Increased oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the risk of COPD and the substitution of alanine 16 with valine (Ala16Val) polymorphism of manganese-superoxide dismutase (Mn-SOD) and the cytosine to thymidine transition of nucleotide -262 (-262C>T) polymorphism of the catalase gene, and the activity of erythrocyte SOD and catalase. The subjects were stable COPD patient ever smokers (n = 165) and healthy controls, matched for age and cigarette consumption. Genotyping of Mn-SOD at Ala16Val and the catalase gene at -262C>T was performed, and the functional activity of SOD and catalase in erythrocytes determined. There were no significant differences in the distribution of the different genotypes or allele frequencies between patients and controls for both the Mn-SOD and catalase genes. Among healthy controls or COPD patients, no differences were observed in erythrocyte SOD and catalase activity, irrespective of genotype. Significantly higher erythrocyte catalase activity was found in COPD patients than in healthy controls. The T/T catalase genotype and Ala/Ala Mn-SOD genotype were uncommon in the present Chinese population. The increase in erythrocyte catalase activity in Chinese patients with chronic obstructive pulmonary disease probably indicates dysfunction of the oxidant/antioxidant defence system, but it is unclear whether this increase is compensatory or a pathogenic factor.

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.