Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families

RATIONALE: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma. OBJECTIVES: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma. METHODS: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models. RESULTS: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values. CONCLUSIONS: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.     

Influence of male sex and parental allergic disease on childhood wheezing: role of interactions

BACKGROUND: Boys have been reported to be more susceptible to childhood wheezing, whereas girls are more susceptible later in life. This difference might be related to both genetic and environmental factors. OBJECTIVE: To investigate the influence of male sex and parental allergic disease on the development of childhood wheezing. METHODS: Infants (n=4089) born in Stockholm were recruited in a prospective study, BAMSE. Data on parental allergic diseases were obtained from questionnaires answered at the children's birth and on symptoms of wheezing at 1, 2 and 4 years of age. Sensitization to inhalant allergens and lung function was investigated at the age of 4 years. RESULTS: Children were classified as having recurrent, transient (n=266), early-onset persistent (n=319) and late-onset wheezing (n=195). Boys were over-represented in all groups of wheezing (odds ratio, OR=1.4-1.5) and both maternal and paternal allergic disease was of importance for the wheezing outcomes. A dominating influence from maternal allergic disease was only seen in children with persistent wheezing. An interaction exceeding additivity was found between male sex and parental allergic disease, particularly in children with persistent wheezing (OR=2.9 and 95% confidence interval, CI 95% 2.1-4.0 for boys with any parental history vs. OR=1.4, CI 95% 1.0-2.1 for girls). Interaction between male sex and parental allergic disease was also observed in children who wheezed at the age of 4 years and were sensitized to inhalant allergens. CONCLUSION: Our data suggest an interaction between male sex and parental allergic disease in childhood wheezing, which may represent a sex-specific genetic influence.     

Increase of asthma in adults in northern Finland?– a report from the FinEsS study

BACKGROUND: According to previous studies, the prevalence of asthma has been lower in Finland than in other Nordic countries. In the present study, we assessed the prevalence of asthma and respiratory symptoms in northern Finland and calculated risk factors for these conditions. METHODS: In November 1995, 7937 randomly selected subjects, 20-69 years of age, in northern Finland were invited to participate in a postal questionnaire survey. Complete answers were received from 6633 subjects (83.6%). RESULTS: Asthma diagnosed by a physician was reported by 6.0%, while 6.3% were using asthma medicines. Asthma was most common in young adults and the elderly. The prevalence of wheezing during the previous 12 months was reported by 19.7%, while wheezing with shortness of breath apart form colds during the previous 12 months was reported by 7.1%. Only small differences between the sexes were found in prevalence of asthma and respiratory symptoms. All symptoms were strongly smoking-dependent. Sixty-three percent of men and 42% of women were current or ex-smokers. Family history of obstructive airway disease was the strongest risk factor for asthma (OR 2.9), while increasing age, smoking, and family history of obstructive airway disease were the most important risk factors for frequent wheeze. CONCLUSIONS: The results indicate that the prevalence of asthma and symptoms associated with asthma in adults in northern Finland is now similar to that observed in Sweden and the other Nordic countries.     

Effect of Traffic-Related Air Pollution on Allergic Disease: Results of the Children's Health and Environmental Research

Purpose

This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children.

Methods

A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children''s Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area.

Results

Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF_25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren.

Conclusions

The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren.     

Severe asthma in childhood: assessed in 10 year olds in a birth cohort study

Background:  Limited information is available regarding the prevalence of severe asthma in children. The present study aimed at investigating the prevalence of severe asthma in an urban child population; secondarily evaluating the applicability of the chosen definition by clinical characteristics. Methods:  Children enrolled in the prospective birth cohort; the Environment and Childhood Asthma Study in Oslo; were reinvestigated at the age of 10 years (n = 1019). A representative population based cohort of 616 children [mean age 10.9 (SD 0.9) years] with lung function measurements at birth was used for prevalence estimates, whereas all 1019 children (154 with current asthma) attending the 10‐year follow‐up were included for verification of the definition of severe asthma. Clinical investigations included spirometry, tests of bronchial hyperresponsiveness, skin prick tests and exhaled nitric oxide. Severe asthma was defined as poorly controlled asthma despite treatment with ≥ 800 μg budesonide or equivalent; assessed by a detailed structured interview. Results:  The population point prevalence at age 10 years of current severe asthma was 0.5% (three of 616) and among children with current asthma 4.5% (three of 67). The 10/154 children identified as suffering from severe asthma more often had severe bronchial hyperresponsiveness (PD₂₀ methacholine <1 μmol) (60%vs 22%, P = 0.015), lower median forced expiratory volume in 1 s/forced vital capacity ratio (93%vs 99%, P = 0.04) and higher body mass index (mean BMI 22.3 vs 18.3, P < 0.001) than nonsevere current asthmatics. Conclusions:  The prevalence of severe asthma was 0.5% in all 10‐year olds, and 4.5% among current asthmatics. The severe asthma definition applied in this study is supported by results of clinical investigations.     

Childhood bronchial asthma in a desert country

A 3 year-study of emergency room visits (total 50,300) to the paediatric clinic of the main teaching hospital in Kuwait revealed that the rates of bronchial asthmatic attacks increased significantly from 8.8% of all visits during the 1st year to 14.9% during the 3rd year. The seasonal distribution of asthmatic attacks showed maximum rates during the winter and minimum values in the summer, giving a very close inverse correlation to temperature and direct correlation to relative humidity. A similar, excellent correlation was seen between asthmatic attacks and upper respiratory infections. Occurrence of atmospheric pollen, which characteristically shows a bi-annual pattern i Kuwait, was not found to correlate with asthma attack rates. Neither was there any demonstrable effect of dust storms on the frequency of asthmatic attacks in the children. Independent of season, the boy to girl ratio among the asthma cases was remarkably constant, around 2:1.     

Risk factors for asthma among children in Maputo (Mozambique)

BACKGROUND: Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique). METHODS: This case-control study included 199 age-matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast-feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child. RESULTS: The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P < 0.0001). Most of the asthmatic children lived in the urban area of Maputo [odd ratio (OR) = 6.73, CI = 3.1-14.0, P < 0.0001], had a parental history of asthma (OR = 26.8, CI = 10.8-68.2, P < 0.0001) or rhinitis (OR = 4, CI = 1.2-13.3, P = 0.005), had at least parent who smoked and were weaned earlier than the nonasthmatic children (OR = 2.4, CI = 1.3-4.4, P < 0.001). CONCLUSION: Childhood asthma was strongly associated with a family history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.     

Prevalence of Bronchial Asthma and Respiratory Symptoms in Schoolchildren in Oslo

During the school year 1980-81 a survey questionnaire was carried out among schoolchildren aged 7 to 15 years in Oslo. The survey population comprised 39,162 children attending compulsory primary school. The questionnaire was distributed to a random sample of 1772 children in 81 classes, forms 1 to 9, and the response rate was 95%. The prevalence of physician-diagnosis of current and cumulative asthma was 1.6% and 3.1%, respectively. Of those with current asthma 68% used asthma drugs regularly. Occasional wheezing and attacks of breathlessness were reported by 9% and 4%, respectively. Wheezing and breathlessness on exposure to pollen (4.5%), animals (3.1%) and exercise (5.5%) was reported more frequently than physician-diagnosis of asthma. The cumulative prevalence of either hay fever, eczema, urticaria or asthma was 17%. More boys than girls under the age of 12 had a physician-diagnosis of asthma.     

Increasing prevalence of asthma over 12 years among dairy farmers on Gotland, Sweden: storage mites remain dominant allergens

BACKGROUND: Earlier studies from several countries have shown that IgE-mediated allergy in rural populations is of considerable importance and that storage mites are dominant allergens. OBJECTIVE: In an epidemiological follow-up study among farmers on the island of Gotland, Sweden in 1996 we wished to investigate the prevalence of respiratory allergy and to find out whether storage mites are still important allergens in a farming environment. METHODS: A questionnaire concerning airway symptoms, social and working conditions and smoking habits was distributed to all Gotland farmers aged 15-65 years and was completed by 1577 (86.7%), of whom 1015 were dairy farmers. Based on the answers, 500 dairy farmers were invited to undergo a medical examination which included a skin-prick test (SPT) and blood sampling for RAST analyses. Prevalence figures (symptoms, RAST and SPT) given for the whole population (n = 1015) were based on the investigation of the 461 farmers who took part in the examination. RESULTS: Immediate onset hypersensitivity was present in 41.7% of the 1015 farmers studied, which is almost the same figure as in 1984 (40.0%). The prevalence of asthma had increased significantly during the previous 12 years (5.3% vs 9.8%), as had asthma in combination with rhinoconjunctivitis (3.7% vs 7.0%). Rhinoconjunctivitis, on the other hand, had not changed significantly (36.5% vs 33.1%) and remained one of the most common symptoms. The prevalence of storage mite allergy in the farming population in 1996 was 6.5% and constituted an important cause of allergic symptoms. CONCLUSION: Over 12 years, Gotland dairy farmers have developed significantly more respiratory symptoms from the lower airways, although the proportion with atopy is unchanged. Storage mites are still dominant allergens for developing allergic disease.     

On early sensitization to allergens and development of respiratory symptoms

BACKGROUND: Various studies have suggested that a sequence of events occurring in childhood may affect the development of asthma in susceptible individuals. We have investigated whether early childhood sensitization to aeroallergens is an important risk factor in the later development of asthma symptoms. OBJECTIVE AND METHODS: In this study we examine this issue in children enrolled in the Tucson epidemiology study of obstructive airways disease, who had at least two allergen skin tests, one before and one after 8 years of age. Respiratory symptom data were available from 12 survey questionnaires, spanning a period of 20 years. During the first, sixth, seventh and eleventh surveys, skin tests were performed with commercially available allergens. CONCLUSION: As compared with children who were sensitized after 8 years of age, children over 8 years who were sensitized to any allergen before age 8 years were significantly more likely to report shortness of breath with wheeze (SOBWZ), wheeze apart from colds or wheeze most days (OR = 4.1 SOBWZ; OR = 3.88 WZ apart from colds; and OR = 2.83 WZ most days). Children who were sensitized after 8 years were no more likely to have the symptoms described above than children who were never found to be sensitized. Based on these results we conclude that early allergic sensitization is a significant risk factor for later development of wheezy symptoms, where as late sensitization is not.     

The genome of equine herpesvirus type 2 harbors an interleukin 10 (IL10)-like gene

A gene was identified within the DNA sequences of theEcoRI DNA fragment N (4.3 kbp) of the genome of equine herpesvirus type 2 (EHV-2) coding for a protein (179 amino acid residues) homologous to the cytokine synthesis inhibitory factor (CSIF; interleukin 10) of the human and mouse, and to the Epstein-Barr virus (EBV) protein BCRF1. This finding is further significant evidence that the interleukin 10 (IL-10) and/or IL-10-like gene can indeed be present in the genomes of members of the herpesviral family.     

Prevalence of bronchial asthma in schoolchildren in Oslo,Norway

In 1993, 4521 schoolchildren in Oslo, Norway, participated in a European study on air pollution and respiratory health. Incorporated in the primary questionnaire were five questions taken from a study performed 12 years earlier on 1772 schoolchildren in the same city. The response rate was 85% in 1993 vs 95% in 1981. The current and cumulative prevalences of doctor-diagnosed asthma in 1993 were 4.2% and 8.0%, respectively, compared to 2.2% (P<0.01) and 3.4% (P<0.01) in 1981. Attacks of breathlessness during the last 3 years were experienced by 7.1% in 1993 and 3.3% in 1981 (P<0.05). Wheezing or breathlessness on exposure to pollen in 1993 and 1981 was reported by 6.1% and 3.7% (P<0.01), respectively; to animals by 4.0% and 2.8% (P<0.05); and to exercise by 10.2% and 4.8% (P<0.01). The prevalence of occasional wheezing and the cumulative prevalence of doctor-diagnosed eczema, urticaria, and hay fever were not significantly altered. To summarize, a higher prevalence of both doctor-diagnosed asthma and symptoms of obstructive airways disease was reported by children attending primary school in Oslo in 1993 than 12 years earlier. No increase was observed in the prevalence of other atopic diseases.     

The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study

BACKGROUND: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. METHODS: Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. RESULTS: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. CONCLUSIONS: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.     

Association of an early respiratory syncytial virus infection and atopic allergy

BACKGROUND: Respiratory syncytial virus (RSV) causes postbronchiolitic wheezing but its role in allergic sensitization is controversial. The purpose of the study was to examine the effect of an early RSV infection on allergic sensitization. METHODS: Seventy-six subjects were examined 6-10 years after hospitalization for RSV infection during the first year of life. Fifty-one subjects (68%) attended clinical studies and 25 filled in a questionnaire. The study protocol included lung function, skin-prick and blood tests. The controls were matched for birth date and sex. RESULTS: Eight per cent of the subjects and 37% of the controls had at least one positive skin-prick test (SPT) (difference -35%, 95% CI -50 to -19%, P < 0.0001). Allergic rhinitis, atopic dermatitis and asthma occurred as often in both groups, but asthma had been diagnosed significantly earlier in the subjects than in the controls [mean age 3.0 years (SD 2.6) and 5.6 years (SD 3.0), difference 2.6 years, 95% CI 0.57-4.65, P = 0.014]. In a logistic regression analysis, RSV infection was associated with negative SPTs. CONCLUSIONS: An early RSV infection results in reduction of SPT positivity but not of occurrence of atopic diseases. This finding might explain why there is less atopic sensitization in countries with a greater probability of acquiring RSV infection at an early age.