Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Socioeconomic risk factors for lung function decline in a general population.

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population. In the Hordaland County Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV(1)/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV(1) (adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL). Low SES was associated with increased lung function decline in males. For females, marital status was more important.

Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS).

BACKGROUND: Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). METHODS: 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990-2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. RESULTS: Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. CONCLUSION: This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.

Joint effect of obesity and TNFA variability on asthma: two international cohort studies.

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.

TNFA -308G>A in two international population-based cohorts and risk of asthma.

Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.

Effectiveness of third-generation chemotherapy on the survival of patients with advanced non-small cell lung cancer in Norway: a national study.

BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation of chemotherapy. METHODS: All patients with ANSCLC in the Cancer Registry of Norway during 1994-2005 were included. Using sales of vinorelbine as an indicator for chemotherapy, annual county utilisation rates were calculated. Survival before and after the general introduction of vinorelbine and associations between survival and variations in utilisation in counties were investigated. In a subgroup, the predictors of having received chemotherapy were explored. RESULTS: Of 24 875 registered patients with lung cancer, 13 757 had ANSCLC. The annual utilisation of the indicator drug in Norway increased from 3.7 to 184.2 g (1998-2005). Median survival increased from 149 to176 days (p<0.001). The adjusted hazard ratio (HR) for a diagnosis after the introduction was 0.93 (95% CI 0.88 to 0.99). County utilisation rates of vinorelbine (increments of 100 mg/1000 inhabitants) were inversely associated with the risk of death (HR 0.84, 95% CI 0.73 to 0.98). County of residence predicted chemotherapy utilisation with odds ratios in the range 0.13 (95% CI 0.1 to 0.19) to 1.04 (95% CI 0.64 to 1.69), a county with traditionally high utilisation as reference. CONCLUSION: Utilisation of third-generation chemotherapy was associated with slightly increased survival of patients with ANSCLC. Geographical and temporal differences in utilisation indicate variable quality of delivered care.

Norwegian population surveys on respiratory health in adults: objectives, design, methods, quality controls and response rates.

BACKGROUND AND AIMS: Quantifying the prevalence of asthma, chronic obstructive pulmonary disease (COPD) and restrictive pulmonary diseases in Norway is needed to document the burden of chronic respiratory inflammatory diseases on disability, health care costs and impaired quality of life. To introduce effective interventions for prevention, cure and care, there is a prerequisite to know the environmental causes. Furthermore, using relevant and precise phenotypes from community-based studies are important for detecting molecular-genetic causes for diseases. METHODS: The Norwegian Population Survey Initiative on Respiratory Health in Adults has, for four decades, applied international standardised methods for the recording of respiratory symptoms, health status, exposure to risk factors, socio-economic factors and the use of health services. Measurements of spirometry, metacholine bronchial responsiveness, transfer factor for carbon monoxide, atopy as well as chest X-ray examinations have been used advocating the internationally accepted methods. All surveys had similar quality controls, supervision and training of the field-worker team. RESULTS: From 1965 to 1999, random population samples, altogether including 178 690 individuals, have been invited by random sampling to seven surveys on respiratory health in the counties of Oslo (39 998 people) and Hordaland (138 692 people). The surveys were initiated in 1964, 1972, 1985, 1988, 1991 and two in 1998. The age span of those invited persons varied from 15 to 74 years at baseline. It included 43 330 women and 135 537 men. Altogether 130 075 (73%) persons participated by returning an answered questionnaire. Spirometry results are available from 41 335 persons at baseline. A biobank for DNA and blood markers has been established. Data from longitudinally clinical-epidemiological studies were available by 2007, for three surveys after 20 years, 10 years and 6-7 years, and also for parts of three other surveys, while one survey has been examined for cause-specific mortality after 30 years. The response rates of the baseline studies varied from 90% to 68% of those invited and, in general, it has declined over 35 years. The response rate of the longitudinal studies with follow-ups also declined with time after the baseline study. CONCLUSIONS: Great challenges for future population-based studies are (i) to keep the participation rates high in community studies; (ii) to standardise the basic clinical-epidemiological methods over decades of follow-up and to systematically transfer these methods into new populations with different languages and cultures and (iii) to focus on important research questions on respiratory health for the community.

What can we learn about asthma and allergy from the follow-up of the RHINE and the ECRHS studies?

OBJECT: The international population-based studies RHINE and ECRHS have provided new insight in the epidemiology and management of asthma, allergy and rhinitis in young adults. The aim of the present review is to focus on longitudinal results with regard incidence and net change of asthma and asthma-like symptoms, risk factors and management of asthma, with special reference to the Nordic-Baltic countries. RESULTS: Asthma and rhinitis are common conditions that are important in a public health perspective. There are gender differences in incidence and remission. A socio-economic gradient that non-atopic asthma is more strongly related to poverty seems to have developed in the last decade. These findings will challenge our welfare states in the future. In addition, occupational, as well as indoor and outdoor environmental exposures, influenced the onset of asthma. The population-attributable risk for adult asthma because of occupational exposures is equivalent to an incidence of new-onset asthma of 250-300 cases per million per year. Genetic factors, allergic sensitisation, gastro-oesophageal reflux, habitual snoring, diet and other factors may also contribute to the onset of asthma and rhinitis. Even though management of asthma has improved, there are still great variations throughout Europe. These findings highlight the key role doctors and nurses play in educating and reviewing management of patients.

Hormonal factors and respiratory health in women--a review.

Sex hormones appear to play an important role in the lung health of women. This is, however, poorly understood and, in most aspects, poorly investigated; and the literature has been contradictory and confusing. This review presents recent research concerning the involvement of sex hormones in respiratory health of adult women, using the population surveys European Community Respiratory Health Survey and Respiratory Health in Northern Europe. Respiratory health varied substantially according to hormonal and metabolic conditions. First, menopause was associated with lower lung function and more respiratory symptoms, especially among lean women. Second, hormonal replacement therapy (HRT) was associated with increased risk for asthma and wheeze; also, this association was particularly strong among lean women. Third, women with irregular menstruations in fertile age had more asthma, particularly allergic asthma, and reduced lung function, independently of body mass index (BMI) and physical activity. The findings were consistent across cultural and geographical borders. Our studies revealed that considering interplay between hormonal and metabolic factors is a clue to understand the effects of female sex hormones on the airways. A BMI of around 24-25 kg/m(2) appeared to be optimal; women with this BMI had no increase in respiratory health problems when reaching menopause or using HRT, and women in fertile age with this BMI had optimal lung function independently of menstrual status. In conclusion, female sex hormones appear to play a most important role for lung health in women. Further research on effects of sex hormones on the airways should take into account potential interplay with metabolic factors.

Relationship of fish and cod oil intake with adult asthma.

BACKGROUND: A diet rich in fish or cod oil might possibly reduce the risk for asthma and atopic diseases. However, previous studies show conflicting results and no studies have assessed the potential long-term effects of childhood fish intake on adult asthma. OBJECTIVE: To investigate whether childhood and adult fish and cod oil intake was related to adult asthma. METHODS: In a large population-based study, Respiratory Health in Northern Europe (RHINE), 16 187 subjects aged 23-54 years answered a postal questionnaire. The relations of fish and cod oil intake with asthma symptoms and asthma were analysed using multiple logistic and Cox regression analyses, with adjustment for gender, adult hayfever, smoking, age, body mass index, household size, dwelling, parental education and centre, and for maternal smoking and family history of hayfever and asthma in a subsample (n=2459). RESULTS: Subjects from Iceland and Norway reported much more frequent intake of fish both in childhood and adulthood as compared with subjects from Sweden, Estonia and Denmark. Current fish intake less than weekly in adults was associated with more asthma symptoms, while more frequent fish intake did not appear to decrease the risk further. No dose-response association was found between childhood fish intake and adult asthma, but those who never ate fish in childhood had an increased risk for asthma and earlier asthma onset. Adult consumption of cod oil had a u-shaped association with asthma, with the highest risks in those taking cod oil never and daily. CONCLUSION: A minimum level of weekly fish intake in adulthood was associated with protection against asthma symptoms in this large North-European multi-centre study. Subjects who never ate fish in childhood were at an increased risk for asthma. Both indicate a possible threshold effect of fish on asthma.

Remission of asthma: a prospective longitudinal study from northern Europe (RHINE study).

The aim of the present study was to investigate the remission rate of adult asthma in a general population sample in relation to age, sex, asthma symptoms, allergic rhinitis and smoking. A follow-up of the random population samples from the European Community Respiratory Health Survey in Northern Europe was conducted from 1999-2001 on 1,153 individuals (aged 26-53 yrs) with reported asthma. Remission was defined as no asthmatic symptoms in two consecutive years and no current use of asthma medication. Remission rates per 1,000 person-yrs were calculated and Cox regression models, adjusting for confounders, were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). An average remission rate of 20.2 per 1,000 person-yrs was found. There was no significant difference according to sex; the remission rates were 21.7 and 17.8 per 1,000 person-yrs in females and males, respectively. An increased remission rate was observed among subjects who quit smoking during the observation period. Subjects not reporting any asthma symptom at baseline had an increased remission rate. In the Cox regression model, ex-smoking (HR 1.65, 95% CI 1.01-2.71) was associated with increased remission rate, and reporting any asthma symptom at baseline was associated with decreased remission rate (HR 0.7, 95% CI 0.40-0.90). In conclusion, the present prospective longitudinal study showed that quitting smoking and the presence of mild disease appeared to favour remission.

Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study.

BACKGROUND: An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented. METHOD: This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness. RESULTS: Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97). CONCLUSIONS: Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing.

Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey.

BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.

Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study.

BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) has defined chronic obstructive pulmonary disease (COPD) as a post-bronchodilator ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) of <0.7. In the first general population based study to apply post-bronchodilator values, the prevalence and predictors of GOLD defined COPD were assessed and the implications of beta2 agonist reversibility testing examined. METHODS: Based on a random population sample, 2235 subjects (77%) aged 26-82 years performed spirometric tests before and 15 minutes after inhaling 0.3 mg salbutamol. RESULTS: The prevalence of GOLD defined COPD was 7.0% (95% confidence interval (CI) 5.9 to 8.0). This estimate was 27% lower than COPD defined without bronchodilatation. One percent of the population had severe or very severe COPD. Compared with women, men had 3.1 (95% CI 2.1 to 4.8) times higher odds for COPD. Subjects with a smoking history of more than 20 pack years had an odds ratio (OR) of 6.2 (95% CI 3.4 to 11.0) for COPD relative to never-smokers, while subjects older than 75 years had an OR of 18.0 (95% CI 9.2 to 35.0) relative to those below 45 years. Subjects with primary education only had an OR of 2.8 (95% CI 1.4 to 5.3) compared with those with university education. Subjects with body mass index (BMI) <20 kg/m2 were more likely than subjects with BMI 25-29.9 kg/m2 to have COPD (OR 2.4, 95% CI 1.1 to 5.3). The adjusted proportion of COPD attributable to smoking was 68%. CONCLUSIONS: These results indicate that community programmes on prevention of COPD should focus on anti-smoking, nutritional aspects, and socioeconomic conditions. The effect of beta2 reversibility testing on prevalence estimates of COPD was substantial.

Maternal atopy and changes in parity.

BACKGROUND: Atopic women tend to have fewer children, although atopy may favour conception. OBJECTIVE: To assess whether atopy is associated with the number of new births and whether changes in parity are associated with a change in atopy in a cohort of young women. METHODS: Women had atopy (defined as the presence of serum-specific IgE against common aeroallergens) measured in the European Community Respiratory Health Study during the years 1991--92 (n=4580). About 9 years later, 2844 (62.1%) were recontacted and 2414 (52.7%) had atopy measured again. RESULTS: Atopic women had fewer children at baseline than non-atopic women but the association disappeared at the end of the follow-up. Atopy tended to increase parity during the follow-up, but in a non-statistically significant way (relative risk=1.08; 0.86-1.35, after adjusting for number of children at baseline, age, length of follow-up, education or social class). Prevalence of atopy during the follow-up changed by the same magnitude whatever the birth cohort and the change in the number of children (P for interaction >0.7). CONCLUSION: Atopic women did not have a significantly higher fertility rate but they may postpone having their first child compared with non-atopic women. We are unable to confirm the hypothesis that atopy in women may decrease with successive pregnancies.

The association between birth size and atopy in young North-European adults.

BACKGROUND: There is evidence that atopic disorders may begin in intra-uterine life; however, studies of birth characteristics and atopy show conflicting results. METHODS: We wanted to investigate the association of birth weight and head circumference with serum total or specific IgE, allergic rhinitis or eczema while addressing the influence of demographic and geographical factors. In this historic prospective cohort study, data were collected from birth records for 1683 men and women born in 1947-1973, from six Nordic-Baltic populations participating in the European Community Respiratory Health Survey. Blood tests for the measurement of serum total and specific IgE were available for 1494 subjects. In multiple regression analyses, adjustments were made for birth length, gender, age, study centre, adult body mass index, level of education, parental and adult smoking. RESULTS There was no association of birth weight (n=1230) and head circumference (n=285) with serum total IgE, specific IgE antibodies, allergic rhinitis or eczema. There were neither significant interactions by gender or age, nor heterogeneity between the study centres in the analyses of birth weight and adult atopy. CONCLUSION: Birth size was not associated with atopy among adults in this large Nordic-Baltic population study.

Incidence of GOLD-defined chronic obstructive pulmonary disease in a general adult population.

SETTING: The incidence of chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has not previously been examined. OBJECTIVE: To estimate cumulative 9-year GOLD-defined COPD incidence in a general adult Norwegian population, to analyse sex, age, smoking habits and residential area as predictors, and to assess the level of underdiagnosis. DESIGN: Based on a random stratified population sample examined in 1987-1988, 908 adults (71%) participated in a follow-up examination in 1996-1997. Associations between risk factors and COPD incidence were examined with logistic regression analyses. RESULTS: The cumulative incidence of COPD among persons at risk in 1987-1988 was 6.1% (95% confidence interval [CI] 4.0-8.1). Adjusted odds ratios (OR) for current smokers and ex-smokers were 9.6 (95% CI 3.6-25.2) and 5.0 (95% CI 1.8-13.8), compared to never smokers. Risk for COPD incidence further increased with pack years. Subjects aged 45-74 had an OR of 9.8 (95% CI 4.3-22.5) relative to those aged 18-44. Sex and residential area were not significantly associated with COPD incidence. Only 43% of the incident cases had physician-diagnosed asthma, bronchitis, emphysema and/or COPD. CONCLUSION: Approximately 6% developed COPD over 9 years. Smoking and aging were important incidence predictors. Our study suggests a substantial underdiagnosis of COPD among adults in this community.

Association of asthma and hay fever with irregular menstruation.

BACKGROUND: There is some evidence that asthmatic women are more likely to have abnormal sex hormone levels. A study was undertaken to determine whether asthma and allergy were associated with irregular menstruation in a general population, and the potential role of asthma medication for this association. METHODS: A total of 8588 women (response rate 77%) participated in an 8 year follow up postal questionnaire study of participants of the ECRHS stage I in Denmark, Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking exogenous sex hormones were included in the analyses (n = 6137). RESULTS: Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to 2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to 2.96)) among women aged 26-42 years. This was also observed in women not taking asthma medication (asthma symptoms: OR 1.44 (95% CI 1.09 to 1.91); hay fever: OR 1.27 (95% CI 1.03 to 1.58); wheeze preceded by hay fever: OR 1.76 (95% CI 1.18 to 2.64)). Irregular menstruation was associated with new onset asthma in younger women (OR 1.58 (95% CI 1.03 to 2.42)) but not in women aged 42-54 years (OR 0.62 (95% CI 0.32 to 1.18)). The results were consistent across centres. CONCLUSIONS: Younger women with asthma and allergy were more likely to have irregular menstruation. This could not be attributed to current use of asthma medication. The association could possibly be explained by common underlying metabolic or developmental factors. The authors hypothesise that insulin resistance may play a role in asthma and allergy.

Insomnia is more common among subjects living in damp buildings.

BACKGROUND: Insomnia is a condition with a high prevalence and a great impact on quality of life. Little is known about the relation between and sleep disturbances and the home environment. AIM: To analyse the association between insomnia and building dampness. METHODS: In a cross-sectional, multicentre, population study, 16 190 subjects (mean age 40 years, 53% women) were studied from Reykjavik in Iceland, Bergen in Norway, Umeå, Uppsala, and Göteborg in Sweden, Aarhus in Denmark, and Tartu in Estonia. Symptoms related to insomnia were assessed by questionnaire. RESULTS: Subjects living in houses with reported signs of building dampness (n = 2873) had a higher prevalence of insomnia (29.4 v 23.6%; crude odds ratio 1.35, 95% CI 1.23 to 1.48). The association between insomnia and different indicators of building dampness was strongest for floor dampness: "bubbles or discoloration on plastic floor covering or discoloration of parquet floor" (crude odds ratio 1.96, 95% CI 1.66 to 2.32). The associations remained significant after adjusting for possible confounders such as sex, age, smoking history, housing, body mass index, and respiratory diseases. There was no significant difference between the centres in the association between insomnia and building dampness. CONCLUSION: Insomnia is more common in subjects living in damp buildings. This indicates that avoiding dampness in building constructions and improving ventilation in homes may possibly have a positive effect on the quality of sleep.