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.

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.

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.

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.

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.

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.

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.

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.

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.

Serum respiratory virus antibodies: predictor of reduced one-second forced expiratory volume (FEV1) in Norwegian adults.

BACKGROUND: The purpose of this cross-sectional study was to investigate whether the presence of serum complement antibodies was associated with reduced one-second forced expiratory volume (FEV1) in adults. METHODS: From a stratified random sample of 18-73 year old adults, we performed measurements of serum complement fixing virus antibodies against influenza type A and B, parainfluenza type 1, 2, and 3, respiratory syncytial virus and adenovirus on 82% (n = 1239). RESULTS: In the crude data, subjects having five of the seven virus antibodies had significantly lower lung function, given as sex-, age- and height-standardized residuals of FEV1 (SFEV1), compared with those without. After adjusting in addition for smoking habits, lifetime smoking consumption and season, the lung function levels were significantly lower in subjects with influenza type B and respiratory syncytial virus antibodies compared to those without (P < 0.01). Increasing influenza and respiratory syncytial virus antibody titres and increasing numbers of virus antibodies, respectively, were related to progressively lower lung function. Subjects with respiratory symptoms but without obstructive lung disease had lower antibody levels than subjects with obstructive lung disease, but higher levels than asymptomatic subjects. In a final multiple linear regression analysis adjusting in addition for respiratory symptom and disease status as well as for the other respiratory virus antibodies, the presence of respiratory syncytial virus antibodies was a significant predictor for reduced SFEV1 (regression coefficient: -0.226; SE = 0.112; P = 0.04). The magnitude of the effect on lung function remained after excluding subjects reporting symptoms of respiratory infection within 3 weeks prior to the examination (regression coefficient: -0.252; SE = -0.218; P = 0.25). CONCLUSIONS: This cross-sectional community study indicates that respiratory syncytial virus infection or re-infection is an independent predictor for reduced lung function in adults of a wide age range.

Respiratory virus antibodies in adults of a Norwegian community: prevalences and risk factors.

BACKGROUND: The aims were to examine prevalences as well as demographic and environmental predictors of respiratory virus antibodies in serum. METHODS: In a cross-sectional study of 18-73 year old Norwegian adults a random stratified sample (n = 1512) was invited to attend an examination at an outpatient clinic. Seven respiratory virus antibodies were assessed by the complement fixation test. RESULTS: The attendance rate was 84%. The most frequent virus antibodies with titre of > or = 1:8 were influenza virus type A with a population standardized prevalence of 44%, adenovirus 25% and influenza virus type B 22%. The prevalences of antibodies against parainfluenza virus type 1, 2 and 3 increased with age. Smokers compared to non-smokers had an adjusted odds ratio (OR) of 1.7 (95% confidence interval [CI]: 1.3-2.4) for having one or more of the seven examined virus antibodies. The presence of one or more of the virus antibodies increased from summer to winter months (adjusted OR = 1.3 per month; 95% CI: 1.2-1.4) and it was higher in occupational dust or gas exposed smokers (adjusted OR = 2.0; 95% CI: 1.1-3.7) compared with unexposed smokers. CONCLUSIONS: Ageing, smoking, occupational dust or gas exposure as well as season of the year may thus be predictors for levels of respiratory virus antibodies in adults. These observations should be taken into account when comparing prevalences of virus antibodies in various communities as well as when examining the relationship between presence of virus antibodies and airway disease.

Tuberculin test variability: using the Norwegian Adrenaline-Pirquet method.

SETTING: Chest Unit, Bergen, Norway. OBJECTIVES: To study the agreement between two Adrenaline-Pirquet tuberculin tests and compare reactivity in groups read after 2, 3 and 4 days. DESIGN: Responders from a random sample of 1200 men and women 20-44 years of age in 1991 were tested with dual Adrenaline-Pirquet skin scratch tests with Norwegian-produced synthetic medium tuberculin and read after 2-7 days. RESULTS: Of 588 subjects dually tuberculin tested, complete agreement existed in 220 (37.4%). A difference of 1 mm one way or the other was observed in 239 (40.6%), whereas a difference of less than 3 mm was found in 567 (96.5%). Using the larger of the two reactions increased the rate of tuberculin positivity (> or =4 mm) by up to 8.4% compared with reading only one of the tests. No statistically significant differences were observed between subjects whose reactions were read after 2, 3 and 4 days. CONCLUSION: Under the non-blinded conditions of this study the dual Adrenaline-Pirquet tuberculin tests demonstrated reproducibility equivalent to the internationally recommended Mantoux test, and appeared to be independent of time of reading within four days.

Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.

BACKGROUND: Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms. OBJECTIVES: This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. METHODS: Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW). RESULTS: The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011). CONCLUSIONS: Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

Tuberculin reactivity: prevalence and predictors in BCG-vaccinated young Norwegian adults.

We studied tuberculin reactivity in young Norwegian adults and its possible dependency on age, gender, previous BCG vaccination, smoking habits, occupational exposure, diet as well as years of education as a measure of socio-economic status. Responders of a random sample of men and women aged 20-44 years living in Bergen, Norway were interviewed and tested withthe adrenaline-Pirquettest with Norwegian-produced synthetic mediumtuberculin at the out-patient chest clinic in the city of Bergen in 1992-1993. Nine hundred and three subjects out of 1200 met for the clinical examination (75%). Five hundred and eighty-eight subjects were tuberculin-tested and read, whereof 95% were BCG vaccinated by age 14. Mean tuberculin reactivity was 4.8 mm (SD: 3.0 mm). A positive reaction (> or = 4 mm) was found in 64%, whereof 7% had a strongly positive reaction (>10 mm). A negative reaction (<4 mm) occurred in 36%, whereof 10% had no reaction (0 mm). Only 30% ofthe females and 36% of the males aged 21--25 years were tuberculin positive 7-12 years after BCG vaccination. Linear regression analysis demonstrated tuberculin reactivity to increase with increasing age, male gender with an increasing sex effect by age, and current smoking. Occupational dust or gas exposure, a diet rich in vitamin C or years of education did not influence tuberculin reactivity significantly.

Hospitalization for lung disease in early childhood and asthma symptoms in young adulthood.

Longitudinal studies have reported an association between early childhood lung disease and adult respiratory disease. This issue has not been addressed in the Nordic countries. We studied the association between hospitalization for lung disease in early childhood and asthma in young adulthood in a Norwegian population sample, while estimating the attributable fraction of childhood hospitalization. A population-based survey in Bergen, Norway included a random sample of 4300 subjects aged 20-44 years, of whom 80% responded. The effect of hospitalization for lung disease before the age of 2 years on asthma in adulthood was analysed by logistic and polytomous logistic regressions, adjusting for related variables. Adjusted attributable fractions were estimated from these models. The risk for different measures of asthma was significantly increased in the 103 persons reporting childhood hospitalization (airways symptoms: OR from 1.9 to 2.9; asthma medication: OR = 2.8). The associations with airways symptoms were stronger in women (OR from 2.6 to 5.3) than in men (OR from 1.4 to 2.4). Given a causal association, adjusted attributable fractions showed that childhood lung disease causing hospitalization explained 4% of asthma symptoms. Early childhood hospitalization for lung disease was related to asthma symptoms in young Norwegian adults, more strongly in women than in men. Only a minor proportion of asthma symptoms in this age group could be related to hospitalization for lung disease in early childhood.

Comparing the adrenaline-Pirquet test with international PPD tuberculin tests.

Several tuberculins, strengths and setting methods are in everyday use. We wanted to compare the Norwegian reference adrenaline Pirquet test with the internationally recommended Mantoux PPD test and Rhoditest. In responders of a random sample of young adults, with randomization of test subjects, we intra-individually compared the adrenaline-Pirquet (aP) test with Norwegian-produced synthetic medium tuberculin (SMT) with either the Mantoux test with PPD 2 tuberculin units (TU) (M2), the Mantoux-PPD 5 TU (M5) or the PPD 2 TU-Rhoditest (Rh). The criteria for a positive reaction were > or = 4mm for the aP test, > or = 10 mm for the M2 test, > or = 6 mm for the M5 test and > or = 2 mm for the Rh test. Strongly positive reactions were defined as aP test > or = 10 mm and M2/M5 test > or = 15 mm. One of the tuberculin tests was positive while the comparison test was negative in 14% of the M2 test group (n = 236), 15% in the M5 test group (n = 162) and 20% in the Rh test group (n = 187). The three PPD tests had positive reactions 3-10 times as often, with a simultaneous negative aP test, than vice versa. Strongly positive reactions occurred in 7% of the aP tests (> or = 10 mm), 32% of the M2 tests (> or = 15 mm) and in 41% of the M5 tests (> or = 15 mm). Receiver operating characteristic (ROC) curves gave the best agreement, with aP test >3mm compared with the M2 and the Rh tests. Regression equations are presented for transformations of the Norwegian reference method of adrenaline-Pirquet results to internationally recommended PPD tests. The international recommendations, globalization in general and the skill of Norwegian public health nurses in performing intra-dermal BCG suggest a future shift to the PPD 2 TU Mantoux test in Norway. Due to the lack of sensitivity and specificity of all tuberculin tests they might be used in targeted tuberculin testing and not as a general screening procedure in a low-incidence tuberculosis area with BCG-vaccinated inhabitants.

Dietary vitamin C intake is inversely related to cough and wheeze in young smokers.

We aimed to investigate whether dietary vitamin C intake, an important antioxidant, is inversely related to self-reported respiratory symptoms in young adults of a community. A random sample of 4300 subjects, aged 20-44 years, living in Bergen, Norway, received a postal questionnaire on respiratory symptoms; 80% responded. Vitamin C intake (mg per week) was estimated from a food-frequency questionnaire asking how often the subject, during the last year, had consumed units of orange juice, oranges, potatoes, carrots and tomatoes. Significant differences in the intake of vitamin C were observed across smoking categories with current smokers having the lowest intake, while there was no variation by gender, age or occupational dust exposure. Dietary vitamin C intake was in univariate analyses inversely related to "morning cough", "chronic cough", "wheeze" and "wheeze ever". After adjusting for gender, age, body mass index, "occupational exposure" pack-years as well as having and stratified on smoking habits in multiple logistic regression analyses, the relationship between dietary vitamin C intake and "cough" and "wheeze" tended to be associated to smoking. The odds ratio (OR) for "morning cough" was 0.68 (95% CI: 0.35-0.95), "chronic cough" OR 0.69 (95% CI: 0.47-1.04) and "wheeze ever" OR 0.75 (95% CI: 0.56-1.01) in current-smokers with dietary vitamin C intake in the upper (> or =395 mg/ week) vs. the lower (<209 mg/week) tertile. The OR for "wheeze" was 0.56 (95% CI: 0.35-0.88) in ex-smokers. The magnitude ofthese effects remained after excluding subjects with supplementary vitamin C intake (n=199) from the statistical analyses. Among young Norwegian adults, having a low prevalence of asthma and high prevalences of smoking-related respiratory symptoms, dietary vitamin C intake may act as an antioxidant and thereby reduce cough and wheeze in smokers having high oxidant stress.

Is birth weight related to lung function and asthma symptoms in Nordic-Baltic adults?

Studies of birth characteristics and respiratory outcomes show contradictory findings. We wanted to investigate the association of birth weight with adult lung function as well as asthma symptoms while addressing the influence of demographic and environmental factors. Data was collected from the birth records of 1683 men and women born in 1947-1973 who were included in 6 Nordic-Baltic population samples investigated within the European Community Respiratory Health Survey (ECRHS). In the adults, an increase in birth weight from below 2500 g to above 4000 g was associated with an increase from 96% to 104% predicted one-second forced expiratory volume (P<0.01) and from 1.00% to 107% predicted forced vital capacity (P<0.01). However, birth weight was not associated with symptoms of asthma. After adjustment for birth length, gender, age, study centre, adult BMI, allergic rhinitis, parental and adult tobacco smoke exposure in multivariate regression analyses, birth weight was not associated with adult lung function or asthma symptoms. Further sub-sample analyses revealed no influence of gestational age, gender, age or geographical area. In this historic prospective cohort study an association was neither found between birth weight and adult lung function nor between birth weight and asthma symptoms.

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.

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.