Background

Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation.

Methods

Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC20 (methacholine concentration that produces 20% fall in FEV1 (forced expiratory volume at 1 second)) sputum cellularity and select Th1/Th2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines.

Results

40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC20 had increased by 2.0 mg/ml; the FEV1 decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV1 component (correlation with interferon-gamma = −0.46, p = 0.005).

Conclusion

Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation.

Background

The use of biomarkers has expanded considerably, as an alternative to questionnaire-based metrics of environmental tobacco smoke (ETS); few studies have assessed the affect of such alternative metrics on diverse respiratory outcomes in children, and we aimed to do so.

Methods

We evaluated various measures of birth-year ETS, in association with multiple respiratory endpoints early years of life, in the novel context of a birth cohort at high risk for asthma. We administered questionnaires to parents, both at the end of pregnancy and at one year of life, and measured cotinine in cord blood (CCot; in 275 children) and in urine (UCot; obtained at 12 months in 365 children), each by radioimmunoassay. Multiple logistic regression was used to assess the association of the various metrics with recurrent wheeze at age 2 and with bronchial hyperresponsiveness (BHR) and asthma at age 7.

Results

Self-reported 3rd trimester maternal smoking was associated with significantly increased risk for recurrent wheeze at age 2 (odds ratio 3.5 [95% confidence interval = 1.2,10.7]); the risks associated with CCot and 3rd trimester smoking in any family member were similar (OR 2.9 [1.2,7.0] and 2.6 [1.0,6.5], respectively). No metric of maternal smoking at 12 months appeared to significantly influence the risk of recurrent wheeze at age 2, and no metric of ETS at any time appeared to significantly influence risk of asthma or BHR at age 7.

Conclusions

Biomarker- and questionnaire-based assessment of ETS in early life lead to similar estimates of ETS-associated risk of recurrent wheeze and asthma.

Objectives

Most western red cedar asthmatics (WRCA) continue to have symptoms even after removal from exposure. Consequently, health-related quality of life (HRQL) is often impaired. The objective of this study was to evaluate the relationship between two measures of AHR and HRQL scores in those with WRCA.

Methods

HRQL was determined by the short form 36 (SF-36) in 46 male, non-smoking individuals with WRCA removed from exposure to western red cedar, on average, 15 years earlier. The relationships between the SF-36 total score and its eight domains with 2 indices from methacholine-stimulated airway hyperresponsiveness (the provocative concentration of methacholine causing a 20% fall in FEV1 [PC20] and bronchial reactivity index [BRI]) were analyzed by the Pearson correlation and multiple linear regression.

Results

PC20 was significantly correlated with the SF-36 total score and its two domains of bodily pain and general health (r = 0.34, 0.40, 0.40, p = 0.023, 0.006, 0.006, respectively). BRI was significantly correlated with bodily pain and general health (r = −0.35, −0.42, p = 0.017, 0.004, respectively); correlations remain significant after adjusting for age, ethnicity, years since diagnosis, years since last exposure and use of inhaled corticosteroid. BRI and other measures of airway responsiveness were not associated with inhaled corticosteroids use.

Conclusions

In Western red cedar asthmatics removed from exposure, measures of airway responsiveness are associated with HRQL.

Background

Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age.

Methods

The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA).

Results

The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = −0.149, p = 0.108).

Conclusion

Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.

Background

T-cell immunoglobulin mucin-3 (TIM3) is a TH1-specific type 1 membrane protein that regulates TH1 proliferation and the development of immunological tolerance. TIM3 and its genetic variants have been suggested to play a role in regulating allergic diseases. Polymorphisms in the TIM3 promoter region have been reported to be associated with allergic phenotypes in several populations. The aims of this study were to examine whether genetic variation in the promoter region of TIM3 influenced transcription of the gene and risk for allergic phenotypes.

Methods

We performed 5' rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. We screened for polymorphisms in the promoter region. Deletion analysis was used to localize the promoter region of TIM3. Genotyping was performed by TaqMan assays in three asthma/allergy population samples.

Results

We found two regions with promoter activity in TIM3. One region was from -214 bp to +58 bp and the other from -1.6 kb to -914 bp relative to the transcription start site. None of the single nucleotide polymorphisms (SNPs) or haplotypes affected the transcriptional activity in reporter gene assays. No association between the SNPs and any phenotype was observed in the study cohorts.

Conclusion

Our findings indicate that SNPs and haplotypes in the TIM3 promoter region do not have a functional effect in vitro and are not associated with allergic diseases. These data suggest that polymorphisms in the TIM3 promoter region are unlikely to play an important role in susceptibility to allergic diseases.

OBJECTIVE:

Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years.

SETTING:

The sample (n=2962) was drawn from six Canadian sites.

DESIGN:

A prevalence study using the European Community Respiratory Health Survey protocol was conducted. Airflow obstruction was assessed by spirometry. Bronchial responsiveness, skin reactivity to allergens and total serum immunoglobulin E were also measured. Logistic regression was used for analysis.

RESULTS:

Airflow obstruction was observed in 6.4% of the sample, not associated with sex or age. The risk of airflow obstruction increased in patients who had smoked and in patients who had lung trouble during childhood. Adjusted for smoking, the risk of airflow obstruction was elevated for subjects with past and current asthma, skin reactivity to allergens, elevated levels of total immunoglobulin E and bronchial hyper-responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a history of asthma, 50% were smokers without asthma, 12% were nonsmokers with asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper-responsiveness increased the prevalence of airflow obstruction in each of these groups.

CONCLUSION:

Smoking and asthma, jointly and individually, are major determinants of obstructive disorders in young adults. Bronchial hyper-responsiveness contributes to obstruction in both groups.

A prospective population-based molecular and conventional epidemiological study of 65.4% of bacteriologically confirmed cases of tuberculosis was carried out on the island of Hong Kong from May 1999 to Oct 2000 by the IS6110-based restriction fragment length polymorphism technique. Eleven of the isolates had five or fewer bands; 24.5% of the remaining 691 isolates belonged to clusters. The estimated proportion of recently transmitted disease was 15 to 20%.

Objective

To describe the outbreak of severe acute respiratory syndrome in Hong Kong.

Design

Descriptive case series.

Setting

Hong Kong, Special Administrative Region, China

Results

The outbreak started with a visitor from southern China on 21 February. At the hospitals where the first cases were treated the disease spread quickly among healthcare workers, and then out into the community as family members became infected. By 1 April, 685 cases had been reported with 16 deaths. Symptoms include high fever and one or more respiratory symptoms (including cough, shortness of breath, and difficulty breathing). Changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent, which has led to empirical treatment with corticosteroids, broad spectrum antiviral agent, and antibacterial cover. There is strong evidence that a novel coronavirus is the pathogen. Precautions for droplet infection should be instituted, including the wearing of masks and rigorous disinfection and hygiene procedures. On 27 March the Department of Health announced drastic measures, including vigorous contact tracing and examination, quarantine of contacts in their homes, and closure of all schools and universities.

Conclusion

The rapidity of the spread of the disease and the morbidity indicate that the agent responsible is highly infectious and virulent. Strict infection control measures for droplet and contact transmission by healthcare workers, a vigilant healthcare profession, and public education are essential for disease prevention.

What is already known on this topicSevere acute respiratory syndrome is a form of atypical pneumonia that originated in southern China and spread globally in a few weeksThe clinical picture, empirical treatment, and the possible mode of disease transmission have been described. The agent responsible is probably a novel coronavirusWhat this study addsThis report gives an account of the daily reported number of cases in Hong Kong, showing how the disease has spread rapidly from healthcare workers to the community, and of the drastic measures the government has finally introduced to attempt to control the diseaseA vigilant healthcare profession, strict infection control measures, and public education are essential to prevent disease disseminationEarly introduction of quarantine procedures for this disease by health authorities should be considered.

Background

Reported prevalence rates of asthma vary within and between countries around the world. These differences suggest environmental factors in addition to genetic factors in the cause of the disease and may provide clues for preventive strategies. We examined the variability of asthma-related symptoms and medication use among adults in 6 sites across Canada (Vancouver, Winnipeg, Hamilton, Montreal, Halifax and Prince Edward Island) and compared our findings with those from sites that had participated in a recent European survey.

Methods

We used the same sampling strategy and standardized questionnaire as those used in the European Community Respiratory Health Survey (ECRHS). The 6 Canadian sites were selected to represent different environments with respect to climate, air pollution and occupational exposure. Community-based samples of 3000 to 4000 people aged 20–44 years were randomly selected in each site. Subjects were asked to complete the questionnaire by mail between March 1993 and November 1994. Prevalence rates (and 95% confidence intervals [CIs]) of asthma symptoms, self-reported asthma attacks and use of asthma medication were compared across the Canadian sites and with sites that had participated in the ECRHS.

Results

The overall response rate of those selected to receive the questionnaire was 86.5% (range 74.5%–92.8%). The prevalence rates of most asthma symptoms varied significantly among the Canadian sites. For instance, 21.9% (Montreal) to 30.4% (Halifax) of the men and 24.0% (Vancouver) to 35.2% (Halifax) of the women reported wheezing in the year before the survey. Depending on the site, 4.4% to 6.3% of the men and 5.2% to 9.5% of the women reported an asthma attack in the last year, and 4.0% to 6.1% of the men and 4.9% to 9.7% of the women were currently using asthma medication. Prevalence rates of symptoms, asthma attacks and medication use did not change with age, but they were higher among women than among men. Compared with the results from the ECRHS sites, those from the Canadian sites were among the highest.

Interpretation

Significant variation in the prevalence of asthma symptoms, asthma attacks and use of asthma medication between Canadian sites and international sites suggests environmental influences. Different combinations of factors in different sites may be responsible for the high prevalence rates and should be the subject of further research to guide clinical management and public health intervention.

Occupational allergic contact dermatitis in 52 forest-workers was caused by sesquiterpene lactones from liverworts (Frullania) and by usnic acid from lichens which grow on various trees including cedar (Thuja). Occupational asthma and rhinitis in 35 wood-workers was caused by wood dust of western red cedar (Thuja plicata). Characteristically, the respiratory symptoms occurred in the evening and at night and not during working hours; inhalation challenge with plicatic acid from the wood provoked immediate, late or dual (combined immediate and late) asthmatic reactions. Another class of compounds, tropolones, derived from Thuja plicata wood, was responsible for dermatitis in a wood-worker. These distinct industrial hazards in two groups of workers at the tree-felling and wood-working levels in the forest-products industry can be identified by clinical history and examination supplemented by specific cutaneous or respiratory clinical investigation.

The result of a double-blind crossover trial with disodium cromoglycate (Intal) in 22 patients, nine with extrinsic asthma and 13 with intrinsic asthma, is reported. While eight extrinsic asthmatics showed considerable symptomatic improvement, only five of the intrinsic group improved while on disodium cromoglycate. Twelve out of 13 patients with symptomatic improvement had associated decrease in airway obstruction as measured by the FEV1.

It is concluded that disodium cromoglycate is useful in the treatment of asthma, particularly of the extrinsic type.

The clinical features and the results of investigations (including immunological tests) of three patients with asthma due to western red cedar are described. Bronchial provocation tests with extract of this wood produced immediate asthmatic reaction in one patient, late asthmatic and peripheral reactions in another and late asthmatic reaction alone in the third. While mild immediate skin reactions were detected in two patients, no late skin reactions were observed. Serum precipitins to this extract were not detected. An attempt was made to identify the responsible allergen in the red cedar extract.