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ObjectiveThe aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys.DesignReported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model.SettingAdult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since.SubjectsIndividuals aged 38–66 years with complete data for BMI (n 1580) and waist circumference (n 1017).ResultsMedian BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25·0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI.ConclusionsFigural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible.

Rationale and objectives: The oral cavity is united with the airways, and thus poor oral health may affect respiratory health. However, data on the interaction of periodontal and respiratory health is limited. We aimed to evaluate whether periodontal health status, assessed by the Community Periodontal Index (CPI), was related to lung function among young and middle-aged adults in two Norwegian cohorts. Methods: Periodontal health status and lung function were measured among 656 participants in the Norwegian part of the European Community Respiratory Health Survey (ECHRS III) and the RHINESSA offspring study. Each participant was given a CPI-index from 0 to 4 where higher values reflect poorer periodontal status. The association between CPI and lung function was estimated with linear regression adjusting for age, gender, smoking, body mass index, exercise, education, use of antibiotics, inhaled medication and corrected for clustering within families. Main results: Participants with CPI 3–4 had significantly lower FEV1/FVC ratio compared to participants with CPI 0, b (95% CI) = -0.032 (-0.055, -0.009). Poorer periodontal health was associated with a significant decrease in the FEV1/FVC ratio with an adjusted regression coefficient for linear trend b (95% CI) = -0.009 (-0.015, -0.004) per unit increase in CPI. This negative association remained when excluding asthmatics and smokers (-0.014 (-0.022, -0,006)). Conclusions: Poorer periodontal health was associated with increasing airways obstruction in a relatively young, healthy population. The oral cavity is united with the airways and our findings indicate an opportunity to influence respiratory health by improving oral health. publishedVersion

The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of “IgE-armed” mast cells have been observed in duodenal mucosa of patients with functional GI complaints. To explore whether total IgE and atopic sensitization were associated with functional GI complaints. Levels of serum total and specific IgE and GI complaints were measured in 161 patients and in a general population sample of 478 persons. Standard inhalant allergens were measured in the patient group, and selected inhalant allergens in the general population. GI complaints were assessed by two standardized questionnaires. The associations between GI complaints and total IgE were analyzed in multiple regression models. GI complaints were positively associated with higher total IgE levels (all: b = 0.028, p = 0.012; patient group: b = 0.038, p = 0.072; general population: b = 0.038, p = 0.005), but negatively associated with atopic sensitization (all: b = −11.256, p = 0.181; patient group: b = −85.667, p

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 pCONCLUSIONS: 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.

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.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P

Background: The protective effect of farm upbringing on allergic rhinitis is well known, but how upbringing in other environments influences the development of allergic rhinitis is scarcely investigated. The aim of this study was to investigate the association between place of upbringing and pet keeping in childhood and allergic rhinitis and nasal symptoms in adulthood. Methods: The population-based Respiratory Health in Northern Europe study includes subjects from Denmark, Norway, Sweden, Iceland, and Estonia born in 19451973. This paper analyses 13,376 participants of the third study wave. Six categories of place of upbringing were defined: farm with livestock, farm without livestock, village in rural area, small town, city suburb, and inner city. Pets in the home at birth and during childhood were recorded. Data were analysed using adjusted logistic regression models. Results: Livestock farm upbringing predicted less adult allergic rhinitis [odds ratio (OR) 0.68, 0.540.85] and nasal symptoms (OR 0.82, 0.680.99) than city upbringing, and an urbanrural gradient with decreasing risk per level of urbanisation was observed (OR 0.92, 0.880.94). Pets in the home at birth (OR 0.78, 0.680.88) and during childhood (OR 0.83, 0.740.93) were associated with less subsequent allergic rhinitis. Pet keeping did not explain the protective effect of place of upbringing. Conclusion: Risk of allergic rhinitis and nasal symptoms in adulthood was inversely associated with the level of urbanisation during upbringing. Pets at birth decreased the risk further, but did not explain the urban rural gradient. Persistent beneficial effects of microbial diversity in early life might be an explanation for the findin, Christensen, S. H., Timm, S., Janson, C., Benediktsdóttir, B., Forsberg, B., Holm, M., . . . Schlünssen, V. (2016). A clear urban–rural gradient of allergic rhinitis in a population-based study in Northern Europe. European Clinical Respiratory Journal, 3(1), 33463. doi:10.3402/ecrj.v3.33463

There is limited knowledge of the prognostic value of quantitative computed tomography (CT) measures of emphysema and airway wall thickness (AWT) on mortality.To examine 8-year mortality in relation to CT-measured emphysema and AWT, and assess if potential impact of these predictors remained after adjustment for lung function.In the Norwegian GenKOLS study of 2003-2005, 947 ever-smokers (49% with COPD) aged 40-85 years performed spirometry and CT examination. Mortality data from 2003-2011 were gathered from the Norwegian Cause of Death Registry. CT emphysema % low-attenuation areas (%LAA) and standardized measure for AWT (AWT-Pi10) were main predictors. We performed Laplace regression for survival data, estimating survival time for specified population percentiles within each emphysema category. Models were adjusted for sex, FEV1, COPD status, age, body mass index, smoking, and inflation level.During 8-year follow-up all-cause mortality rate was 15%. Although 4% of the subjects with %LAA less than 3 died, 18% with %LAA 3-10 and 44% with %LAA greater than or equal to 10 died. After adjustment, the comparable percentile subjects with medium and high emphysema had 19 months shorter survival than subjects who died in the lowest emphysema category. Subjects with %LAA greater than or equal to 10 had 33 and 37 months shorter survival than the lowest emphysema category with regard to respiratory and cardiovascular mortality, respectively. No significant associations were found between %LAA and cancer and lung cancer mortality. AWT did not predict mortality independently, but a positive interaction with emphysema was observed.AWT affected mortality with increasing degree of emphysema, whereas CT measure of emphysema was a strong independent mortality predictor.

BACKGROUND: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception.METHODS: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family.RESULTS: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries.CONCLUSIONS: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.

Background: There is limited and conflicting evidence on the effect of menopause on asthma. Objectives: We sought to study whether the incidence of asthma and respiratory symptoms differ by menopausal status in a longitudinal population-based study with an average follow-up of 12 years. Methods: The Respiratory Health in Northern Europe study provided questionnaire data pertaining to respiratory and reproductive health at baseline (1999-2001) and follow-up (2010-2012). The study cohort included women aged 45 to 65 years at follow-up, without asthma at baseline, and not using exogenous hormones (n = 2322). Menopausal status was defined as nonmenopausal, transitional, early postmenopausal, and late postmenopausal. Associations with asthma (defined by the use of asthma medication, having asthma attacks, or both) and respiratory symptoms scores were analyzed by using logistic (asthma) and negative binomial (respiratory symptoms) regressions, adjusting for age, body mass index, physical activity, smoking, education, and study center. Results: The odds of new-onset asthma were increased in women who were transitional (odds ratio, 2.40; 95% CI, 1.09-5.30), early postmenopausal (odds ratio, 2.11; 95% CI, 1.06-4.20), and late postmenopausal (odds ratio, 3.44; 95% CI, 1.31-9.05) at follow-up compared with nonmenopausal women. The risk of respiratory symptoms increased in early postmenopausal (coefficient, 0.40; 95% CI, 0.06-0.75) and late postmenopausal (coefficient, 0.69; 95% CI, 0.15-1.23) women. These findings were consistent irrespective of smoking status and across study centers. Conclusions: New-onset asthma and respiratory symptoms increased in women becoming postmenopausal in a longitudinal population-based study. Clinicians should be aware that respiratory health might deteriorate in women during reproductive aging.

Background There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar. Aims To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD. Methods A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed. Results Gum bleeding always/often was significantly associated with >= 3 asthma symptoms (OR 2.58, 95% CI 2.10-3.18), asthma (1.62 [1.23-2.14]) and self-reported COPD (2.02 [1.283.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (>= 3 symptoms: gum bleeding sometimes 1.42 [1.25-1.60], often/always 2.58 [2.10-3.18]), and there was no heterogeneity between centres (p(heterogeneity) = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p(interaction) = 0.004). Conclusions A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions. * Shared last authorship

The early life environment appears to have a persistent impact on asthma risk. We hypothesize that environmental factors related to rural life mediate lower asthma prevalence in rural populations, and aimed to investigate an urban-rural gradient, assessed by place of upbringing, for asthma. The population-based Respiratory Health In Northern Europe (RHINE) study includes subjects from Denmark, Norway, Sweden, Iceland and Estonia born 1945–1973. The present analysis encompasses questionnaire data on 11,123 RHINE subjects. Six categories of place of upbringing were defined: farm with livestock, farm without livestock, village in rural area, small town, city suburb and inner city. The association of place of upbringing with asthma onset was analysed with Cox regression adjusted for relevant confounders. Subjects growing up on livestock farms had less asthma (8%) than subjects growing up in inner cities (11%) (hazard ratio 0.72 95% CI 0.57–0.91), and a significant urban-rural gradient was observed across six urbanisation levels (p = 0.02). An urban-rural gradient was only evident among women, smokers and for late-onset asthma. Analyses on wheeze and place of upbringing revealed similar results. In conclusion, this study suggests a protective effect of livestock farm upbringing on asthma development and an urban-rural gradient in a Northern European population. publishedVersion

Background Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. Methods Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8–10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. Results Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. Conclusions This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25–55 years. In logistic and linear multilevel mixed models we adjusted for participants’ characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry.Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34–4.32 mL per year), more consistent in females (ptrend 0.025) than in males (ptrend 0.14). Asthma (OR 0.85, 95% CI 0.79–0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82–0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (pinteraction 0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors.Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.

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.

Dietary patterns offer an alternative to the analysis of individual foods or nutrients in nutritional epidemiological studies. The aim of the present study was to identify dietary patterns common to different European countries and examine their associations with asthma. In five study centres (two in Germany, two in the UK and one in Norway), 1174 adults aged 29–55 years completed a FFQ and respiratory symptoms questionnaire. A meta-analytic approach was used to identify the dietary patterns and analyse them in relation to current asthma, asthma symptoms and bronchial responsiveness (BHR). Two patterns emerged, generally correlating with the same foods at different centres: one associated with intake of meats and potatoes; the other with fish, fruits and vegetables. There was no evidence that the fish, fruits and vegetables pattern was associated with asthma (OR 1·11 (95 % CI 0·93, 1·33)), symptom score (ratio of means 1·07 (0·98, 1·17)) or BHR (regression coefficient − 0·01 ( − 0·12, 0·10)), though these CI appeared to rule out large protective effects of consuming these foods. There was no overall evidence that the meat and potato pattern was associated with asthma (OR 1·02 (0·79, 1·31)), symptom score (ratio of means 1·07 (0·84, 1·36)) or BHR (regression coefficient − 0·08 ( − 0·27, 0·10)), but there was heterogeneity between centres in the association with symptom score: a negative association at the two German centres; a positive association at the others. Heterogeneity in a multi-centre observational study of diet could suggest alternative explanations for apparent effects of diet, such as uncontrolled confounding.

Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects.This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI).Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center.Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction).05).Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

Introduction: Utilisation of healthcare resources because of pulmonary diseases have previously been presented according to lung function or symptom severity. We aimed to compare the associations of symptoms and lung function to healthcare and social service utilisation in subjects with self-reported obstructive lung diseases (OLDs) (asthma, chronic obstructive pulmonary disease, chronic bronchitis, emphysema). Materials and Methods: Of 2819 participants aged 27–82 years in the Hordaland County Respiratory Health Survey, 200 subjects (7.1%) self-reported OLD. They answered 13 questions on respiratory symptoms and 5 questions on use of healthcare and social services. Altogether, 161 participants (81%) completed post-bronchodilation spirometry. Results: Use of anti-asthmatic drugs, regular physician's appointment, sick leave payment for the last 12 months, hospital admission for the last 12 months and disability pension were reported by 68%, 63%, 18%, 8% and 7% of those with self-reported OLD, respectively. Twenty per cent of subjects with self-reported OLD had not received any healthcare or social services. In adjusted multivariate logistic regression analyses, increase in the respiratory symptom score was significantly associated with more healthcare and social services. Lower forced expiratory volume in 1 s in % predicted, however, was not significantly associated with more use of healthcare and social services. Conclusion: The majority (80%) of subjects in a general population with self-reported OLD received healthcare services. The utilisation of healthcare and social services was strongly associated to the burden of respiratory symptoms, and, to a lesser degree, to the level and pattern of lung function. Please cite this paper as: Nielsen R, Johannessen A, Bakke PS, Askildsen JE, Omenaas ER and Gulsvik A. Aspects of healthcare utilisation in self-reported obstructive lung disease. The Clinical Respiratory Journal 2009; 3: 34–41.

Background: Chemotherapy is the primary treatment option for patients with advanced non-small cell lung cancer (ANSCLC). We investigated whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with ANSCLC, and explored geographic and temporary variations of the utilisation of chemotherapy. Methods: We included all patients with ANSCLC in the national Cancer Registry of Norway during 1994-2005. Using sales of vinorelbine as an indicator for third-generation chemotherapy we calculated annual county utilisation rates. We compared survival before and after the general introduction of third-generation chemotherapy and investigated associations between survival and variations of chemotherapy utilisation in Norwegian counties. In a subgroup, we compared survival of patients with and without a registered chemotherapy procedure code and explored predictors of having received chemotherapy. Results: Of 24875 registered patients with lung cancer, 13757 had ANSCLC. The annual utilisation of the indicator drug in Norway increased from 3.7 (1998) to 184.2 grams (2005). Variations in utilisation across counties diminished threefold during 1999-2005. Median survival increased from 149 to176 days (P

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/m2 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. Please cite this paper as: Real FG, Svanes C, Macsali F and Omenaas ER. Hormonal factors and respiratory health in women – a review. The Clinical Respiratory Journal 2008; 2: 111–119.

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, transferfactor for carbonmonoxide, atopy as well as chest X-ray examinations have been used advocating the internationally accepted methods. All surveys had similar quality controls, supervisions and training of the fieldworker 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. Please cite this paper as: Gulsvik A, Humerfelt S, Bakke PS, Omenaas ER and Lehmann S. Norwegian population surveys on respiratory health in adults: objectives, design, methods, quality controls and response rates. The Clinical Respiratory Journal 2008; 2: 10–25.

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.

Objective: Some studies have shown an association between lower maternal age at delivery and increased asthma in children and young adults. It is unclear whether this represents an effect of maternal ageing or a protective effect of siblings. In a North-European population based study, we investigated whether mother's age at delivery was associated with risk for asthma and hay fever in adult offspring, taking into account relevant confounders. Methods: A total of 16,190 subjects (74%) aged 23-54yr answered a postal questionnaire in a follow-up of the European Community Respiratory Health Survey (ECRHS I). Results: The associations of maternal age at delivery with hay fever, respiratory symptoms and diagnosed asthma were analysed using logistic regression, adjusting for household size, dwelling, parental education, centre, gender, adult hay fever, smoking, age and body mass index (BMI). The adjusted odds ratios (95% CI) for wheeze with breathlessness, wheeze without a cold and asthma in the offspring were 0.94 (0.90-0.99), 0.89 (0.86-0.94) and 0.92 (0.88-0.97), respectively, per 5yr increase in maternal age. No heterogeneity between centres was found (p = 0.84). The estimates remained similar in sub-sample analyses when adjusting for siblings, maternal smoking (n = 3109) and for birth weight (n = 1686). Hay fever was more common among those with the youngest and oldest mothers. Conclusions: In this large North-European multi-centre study, asthma was less common with increasing maternal age. This effect was consistent between centres and persisted with adjustment for several potential confounders, suggesting that the association may possibly be explained by biological changes related to maternal ageing.

Aim: Diet might modulate lung function decline. We assessed the relationship between baseline dietary intake and 13 year lung function decline in European adults. Methods: In 2000, adults from Norway, Germany and the UK, from the European Community Respiratory Health Survey (ECRHS) answered questions on respiratory health, and had the following spirometric measurements: Forced vital capacity (FVC), forced exhaled volume in 1 second (FEV1), from which the ratio FEV1/FVC, FEV1 below lower limit of normal (FEV1 Results: 733 individuals (mean age 43.5 ± 6.6 years at baseline) were included. A per-tertile increase in vitamin C intake was associated with a -3.74 mL/year lower decline in FEV1 (95% CI -7.29, -0.20). Per-tertile increase in pizza intake was associated with a more accelerated FEV1 and FVC decline (5.63 ml/year (95% CI 2.69, 8.57); 4.65mL/year (95% CI 0.88, 8.41) respectively). These associations remained statistically significant after controlling for multiple testing. In ex-smokers, a per-tertile increase in total fruit intake at baseline was associated with a lower decline in FEV1 (-4.91 mL/year (95% CI -9.68, -0.13) and FVC (-19.45 mL/year (95% CI-32.99, -5.91). Conclusion: Dietary intake of vitamin C and total fruit intake may slow down lung function decline in adults.

Introduction: The prevalence of allergy is lower in rural than in urban areas, but the urban-rural difference in asthma prevalence remains unresolved. It is particularly important to investigate environmental patterns, as they will help to explain the emergence of asthma and to clarify the unsolved aetiology. We hypothesize that environmental factors related to farming may mediate a lower asthma prevalence in rural populations. Aim: To investigate the urban-rural gradient of asthma assessed by place of upbringing. Methods: RHINE (Respiratory Health In Northern Europe) is a prospective population-based cohort study of 9,841 adult men and women from Denmark, Norway, Sweden, Iceland and Estonia. Questionnaire data from follow-up in 2010 were analysed by Cox regression adjusted for potential confounders. Asthma was defined as reporting either asthma or doctor-diagnosed asthma. Place of upbringing was operationalised into six groups: farm with livestock, farm without livestock, village in rural area, small town, suburb of city and inner city. Results: Livestock farm dwellers were less likely to suffer from asthma thancity dwellers (HR 0.72 95% CI 0.56-0.93), but no urban-rural gradient was observed across the six levels of urbanisation. Conclusions: Our study did not support an urban-rural gradient of asthma in a Northern European population, but environmental factors related to livestock farming play some role that needs to be further explored.

Rationale There is some evidence that maternal smoking increases susceptibility to personal smoking's detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning's unhealthy effects. Methods The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent's educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection < 5 years, born during winter months, maternal age at birth > 35 years) was investigated. Main Results Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3-1.6), adult-onset asthma (1.5 [1.2-1.8]) and self-reported COPD (1.7 [1.3-2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: = 4 years 1.6 [1.2-2.1]). The association of wheeze with cleaning activity >= 4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5-2.3] vs. 1.3 [0.96-1.8]; pinteraction 0.035). Conclusions Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

Summary Background Some studies have shown a higher prevalence of asthma in elite athletes as compared to the general population. It is inconclusive to what extent certain sport categories are especially affected. The present study offered a unique opportunity to assess these differences in asthma prevalence in the general population and elite summer athletes from a wide range of sport disciplines across various geographical areas. Methods Cross-sectional data for 1568 general population participants from the European Community Respiratory Health Survey II and 546 elite athletes from the Global Allergy and Asthma European Network Olympic study from three European countries were analyzed. Using logistic regression, the asthma risks associated with athlete sport practice, endurance level and aquatic sport practice, respectively, were investigated. Results Athletes in the highest endurance category had increased risk of doctor-diagnosed asthma (OR 3.5; 95% CI 1.7–7.5), asthma symptoms (OR 3.0; CI 1.5–6.0) and asthma symptoms or medication use (OR 3.5; CI 1.8–6.7) compared to the general population. Aquatic athletes were at increased risk of doctor-diagnosed asthma (OR 2.0; CI 1.1–3.9), asthma symptoms (OR 2.6; CI 1.3–5.0) and asthma symptoms or medication use (OR 2.3; CI 1.2–4.4) when compared to individuals not involved in aquatic sports. Regarding the entire athlete population, no increase in asthma was found when compared to the general population. Conclusions Practice of very high endurance and aquatic sports may be associated with increased asthma risks. Athlete participation as such showed no association with asthma risk.

Summary Failure to follow management guidelines may result in impaired health care. We aimed to overview physicians’ management of acute and stable asthma and chronic obstructive lung disease (COPD) in the Nordic countries based on scientific reports during the last 10 years. Strategies to improve asthma management should consider applying more frequently good quality spirometry in diagnosing asthma and COPD. There still appear to be an under-use of glucocorticosteroids in acute as well as in stable disease in the Nordic countries, especially among asthmatic patients. An over prescription of antibiotics in asthma patients were observed. In COPD patients there are uncertainty in management with under use of ipratropiumbromid and inappropriate use of corticosteroids as well as inadequate knowledge about nebulizing systems, dosing of medicines, monitoring severity of disease and tools for quality control. Further improvement may include educational approaches like multidisciplinary approach for medical students and self-learning groups of doctors. Modern Internet technology and telemedicine may be new ways to proceed in improving health care for patients with asthma and COPD.

International guidelines promote the use of post-bronchodilator spirometry values in the definition and severity classification of chronic obstructive pulmonary disease. However, post-bronchodilator reference values have not yet been developed.To derive reference values for post-bronchodilator forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and to compare these reference values with locally derived and existing pre-bronchodilator reference values.Based on a random sample of a general adult population, 2,235 subjects (70% of invited subjects) performed spirometry with reversibility testing. A reference population of healthy never-smokers constituted 23% of the study population (n=515). Reference values for median and lower-limit-of-normal pre- and post-bronchodilator lung function and bronchodilator response were modeled using quantile regression analyses.The reference population had equal proportions of men and women in the age range 26-82 yr. Both FEV1 and FVC decreased with age and increased with height. FEV1/FVC decreased with age, although this trend was not statistically significant for men after bronchodilatation. Linear models gave the best overall fit. Lower-limit-of-normal post-bronchodilator FEV1/FVC exceeded 0.7 for both sexes. Post-bronchodilator prediction equations gave higher predicted FEV1 and FEV1/FVC than both locally derived and existing pre-bronchodilator equations. The bronchodilator response decreased with age.The present study is the first to develop reference values for post-bronchodilator lung function. Post-bronchodilator prediction equations can facilitate better management of patients with chronic obstructive pulmonary disease by avoiding falsely high FEV1% predicted with a subsequent underestimation of disease severity.

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.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.Subjects living in damp housing (18%) had a significantly (p0.001) 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).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.

Background Improving health-related quality of life (HRQOL) is important for patients with coronary artery disease (CAD). However, few clinicians measure HRQOL in clinical practice. More commonly used are two provider-based measures of CAD, the Canadian Cardiovascular Society (CCS) and the New York Heart Association (NYHA). We explored the relationship of these two provider-based measures with two self-reported HRQOL questionnaires, the Seattle Angina Questionnaire (SAQ) and the Short Form 36 (SF-36). Methods Included were 753 outpatients (74% were men) admitted for elective cardiac catheterization. HRQOL, CCS class, and NYHA status were measured. Results We found significant associations of CCS and NYHA with HRQOL concerning physical dimensions, but weaker associations for other important dimensions. We also observed weaker associations in women than men, not being previously reported. Conclusions HRQOL instruments add broader information in patients with CAD and should supplement provider-based measures. Further research is needed on possible implications of the observed sex differences.

Welding-related asthma is well recognised but less is known about rhinitis in relation to welding. The aim here, was to study associations between welding, rhinitis and asthma in a general population sample, and factors influencing selection into and out of a welding occupation.Adult-onset asthma and non-infectious rhinitis were investigated in the international multicentre population-based Respiratory Health in Northern Europe (RHINE) study, including 16 191 responders aged 26–54 years. Ever welding (n=2181), welding >25% of working time (n=747), and welding in stainless steel >6 months (n=173) were assessed by questionnaire. Subjects with rhinitis or asthma onset when aged Rhinitis incidence was higher among welders (hazard ratio (HR) 1.4, 95% CI 1.3–1.6), consistent in men and women, and across centres (pheterogeneity=0.4). In men, asthma incidence was higher among welders (HR 1.4, 95% CI 1.04–1.97). Quitting welding was indicated higher after adult-onset rhinitis (HR 1.1, 95% CI 1.0–1.3).Adult-onset rhinitis and asthma was higher among welders, consistent across population samples from Northern Europe. No pre-employment selection was found, whereas selection out of welding jobs was suggested.

The objective of this longitudinal study was to estimate the incidence rate of asthma, and to compare the incidence between subjects with or without baseline reporting of certain respiratory symptoms. A follow-up of the random population samples in the European Respiratory Health Survey (ECRHS) in Sweden, Norway, Denmark, Iceland and Estonia was conducted in 1999-2001, in a population aged 30-54 yrs at follow-up (n=14,731). Asthma was defined as reporting either asthma or physician-diagnosed asthma, and a reported year when asthma symptoms were first noticed. Incidence rates, incidence rate ratios and hazard ratios were calculated with 95% confidence intervals. The incidence rate of asthma was 2.2 cases per 1,000 person-yrs. The incidence was higher among females (2.9 cases.1,000 person-yrs(-1)) than among males (1.5 cases.1,000 person-yrs(-1)). When subjects with baseline reporting of wheezing were excluded, the incidence rate decreased to 1.7 cases.1,000 person-yrs(-1), with a further decrease to 1.5 cases.1,000 person-yrs(-1) after exclusion of subjects with wheezing, nocturnal dyspnoea, chest tightness and cough. There was a strong association between onset of asthma and wheezing at baseline. In this prospective, population-based study, the incidence rate of asthma in the whole population sample ranged 1.5-2.2.1,000 person-yrs(-1), with a higher incidence range among females. The incidence was dependent on the extent to which subjects with respiratory symptoms were excluded from follow-up. Hence, for comparability between studies, the exclusion criteria in the follow-up population must be stated.

The impact of active smoking, passive smoking, and obesity on habitual snoring in the population is mainly unknown. We aimed to study the relationship of habitual snoring with active and passive tobacco smoking in a population-based sample. A total of 15,555 of 21,802 (71%) randomly selected men and women aged 25-54 years from Iceland, Estonia, Denmark, Norway, and Sweden answered a postal questionnaire. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was more prevalent among current smokers (24.0%, p0.0001) and ex-smokers (20.3%, p0.0001) than in never-smokers (13.7%). Snoring was also more prevalent in never-smokers exposed to passive smoking at home on a daily basis than in never-smokers without this exposure (19.8% vs. 13.3%, p0.0001). The frequency of habitual snoring increased with the amount of tobacco smoked. Active smoking and passive smoking were related to snoring, independent of obesity, sex, center, and age. Ever smoking accounted for 17.1% of the attributable risk of habitual snoring, obesity (body mass indexor = 30 kg/m(2)) for 4.3%, and passive smoking for 2.2%. Smoking, both current and ex-smoking, is a major contributor to habitual snoring in the general population. Passive smoking is a previously unrecognized risk factor for snoring among adults.

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 (≥395 mg/week) vs. the lower (

Objectives This study assessed the effect of exposure to hairdressing chemicals on total and allergen-specific serum immunoglobulin E (IgE) in hairdressers. Methods The study was based on a questionnaire sent to 100 hairdressers (91% responding) and a reference group of 95 office workers (84% responding). The questionnaire sought information on allergy, respiratory symptoms during the past year, work conditions (exposure), and smoking habits. The hairdressers were divided into two groups, one of high exposure and another of low exposure. Total serum IgE and allergen-specific IgE towards the most prevalent airborne allergens were analyzed. Results The serum levels of total IgE were significantly higher among the highly exposed hairdressers than among the office workers. The prevalence of asthma-like respiratory symptoms during the past year was significantly higher among the highly exposed hairdressers than among the office workers. The total serum IgE level was significantly higher among the hairdressers than among the office workers (101 versus 51 IU/ml blood), but this difference disappeared after adjustment for age, atopy, and smoking. A total of 5.5% of the hairdressers versus none of the office workers had specific serum IgE antibodies towards latex. There were no differences in general allergy (Phadiatop(r)) among the hairdressers and office workers. Conclusions Serum levels of total IgE were significantly higher among highly exposed hairdressers than among office workers. The relationship could not be completely explained by such covariables as age, smoking, or sensitization to latex allergens.

Studies using mothers’ self-reported information on birth and pregnancy characteristics are common, but the validity of such data is uncertain. We evaluated questionnaire data from the RHINE III study on reproductive health provided by 715 mothers from Bergen, Norway, about their 1629 births between 1967 and 2010, using the Medical Birth Registry of Norway (MBRN) as gold standard. Validity of dichotomous variables (gender, preterm birth [42 weeks’ gestation], induction of labour, forceps delivery, vacuum delivery, caesarean section, were assessed by sensitivity, specificity, positive and negative predictive values (PPV and NPV) and Cohen’s kappa. Paired t-test, Pearson’s correlation coefficient and Bland-Altman plots were used to validate birthweight, stratified by mother’s level of education, parity, birth year and child’s asthma status. Child’s gender and caesarean section showed high degree of validity (kappa = 0.99, sensitivity and specificity 100%). Instrumental delivery and extremely preterm birth showed good agreement with sensitivity 75–92%. Preterm birth and induction of labour showed moderate agreement. Post-term delivery was poorly reported. The validity appeared to be independent of recall time over 45 years, and of the child’s asthma status. Maternally reported birth and pregnancy information is feasible and cheap, showed high validity for important birth and pregnancy parameters, and showed similar risk-associations compared to registry data.

To investigate whether guided deep breathing using a device improves breathlessness, quality of life, and breathing pattern in moderate and severe stage of chronic obstructive pulmonary disease (COPD).In total, 150 patients participated in a double-blind randomized controlled trial in a four-week intervention and a four-month follow-up. Participants were randomized into a guided deep breathing group (GDBG), music listening group (MLG), or sitting still group (SSG). The patients' symptom score using the St George's Respiratory Questionnaire (SGRQ), and a Global Rating Change scale (GRC) was applied to measure breathlessness as primary outcome. The activity score and impact score of SRGQ, and breathing pattern were secondary outcomes.Positive effects of the GDBG were detected in GRC scale in breathlessness at four weeks (p=0.03) with remaining effect compared to MLG (p=0.04), but not to SSG at four months follow-up. GDBG showed positive effect for respiratory rate (p0.001) at four weeks follow-up. A positive significant change (p0.05-0.01) was found in all groups of SGRQ symptom score.GDBG had a beneficial effect on respiratory pattern and breathlessness. MLG and SSG also yielded significant improvements.Guided deep breathing may be used as a self-management procedure.

The aim of the study was to identify genetic variants associated with refined asthma phenotypes enabling multiple features of the disease to be taken into account. Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (the European Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, gathered from questionnaires and clinical examination, were used. A genome-wide association study was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n=3474). The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p1.25 × 10(-7)) were observed between "active adult-onset nonallergic asthma" and rs9851461 flanking CD200 (3q13.2) and between "inactive/mild nonallergic asthma" and rs2579931 flanking GRIK2 (6q16.3). Borderline significant results (2.5 × 10(-7)p8.2 × 10(-7)) were observed between three single nucleotide polymorphisms (SNPs) in the ALCAM region (3q13.11) and "active adult-onset nonallergic asthma". These results were consistent across studies. 15 SNPs identified in previous genome-wide association studies of asthma have been replicated with at least one asthma phenotype, most of them with the "active allergic asthma" phenotype. Our results provide evidence that a better understanding of asthma phenotypic heterogeneity helps to disentangle the genetic heterogeneity of asthma.

BACKGROUND: The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation.OBJECTIVE: Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood.METHODS: Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864 subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration.RESULTS: Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61).CONCLUSION: This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.

OBJECTIVES: In a large population-based study among adults in northern Europe the relation between occupational exposure and new-onset asthma was studied. METHODS: The study comprised 13 284 subjects born between 1945 and 1973, who answered a questionnaire 1989-1992 and again 1999-2001. Asthma was defined as 'Asthma diagnosed by a physician' with reported year of diagnose. Hazard ratios (HR), for new-onset adult asthma during 1980-2000, were calculated using a modified job-exposure matrix as well as high-risk occupations in Cox regression models. The analyses were made separately for men and women and were also stratified for atopy. RESULTS: During the observation period there were 429 subjects with new-onset asthma with an asthma incidence of 1.3 cases per 1000 person-years for men and 2.4 for women. A significant increase in new-onset asthma was seen for men exposed to plant-associated antigens (HR = 3.6; 95% CI [confidence interval] = 1.4-9.0), epoxy (HR = 2.4; 95% CI = 1.3-4.5), diisocyanates (HR = 2.1; 95% CI = 1.2-3.7) and accidental peak exposures to irritants (HR = 2.4; 95% CI = 1.3-4.7). Both men and women exposed to cleaning agents had an increased asthma risk. When stratifying for atopy an increased asthma risk were seen in non-atopic men exposed to acrylates (HR = 3.3; 95% CI = 1.4-7.5), epoxy compounds (HR = 3.6; 95% CI = 1.6-7.9), diisocyanates and accidental peak exposures to irritants (HR = 3.0; 95% CI = 1.2-7.2). Population attributable risk for occupational asthma was 14% for men and 7% for women. CONCLUSIONS: This population-based study showed that men exposed to epoxy, diisocyanates and acrylates had an increased risk of new-onset asthma. Non-atopics seemed to be at higher risk than atopics, except for exposure to high molecular weight agents. Increased asthma risks among cleaners, spray painters, plumbers, and hairdressers were confirmed.

Background This paper reviews evidence and quality of Systematic Reviews (SRs) on the effects of breathing control exercises (BCEs) and respiratory muscle training (RMT) on breathlessness/dyspnea and other symptoms, and quality of life (QOL) for individuals with chronic obstructive pulmonary disease (COPD). Methods A search for BCE and RMT literature in COPD published between January 1, 2002 and December 31, 2013 was performed in the following databases: PubMed, Ovid, CINAHL, PsycINFO, AMED, Cochrane and PEDro. The AMSTAR criteria were used to evaluate quality. Results After reviewing 642 reports, seven SRs were identified on RMT and BCEs. Three SRs were of high quality, three were of moderate quality, and one was of low quality. Two high-quality SRs reported significantly beneficial effects of RMT on dyspnea, and one reported significant effects on disease-specific QOL and fatigue. In these SRs, pooled data analyses were performed with three to fourteen single randomised control trials (RCTs) included in the analysis. In one of the SRs the quality of the single RCTs were rated by the authors to be between 5–7 (with10 best) and in the other one the quality of the single RCTs were rated to be between 30-83% of the maximum score. One high-quality SR found a significant positive effect of BCE based on pooled data analysis with two single RCTs in regard to pursed-lip breathing (PLB) on breathlessness. In this SR, one single RCT on diaphragmatic breathing (DB) and another one on yoga breathing (YB) showed effect on disease-specific QOL. The single RCTs included in the SR were rated by the authors in the SRs to be of low and moderate quality. Conclusions Based on three high-quality SRs performing pooled data analyses, there is evidence that RMT has effect on breathlessness, fatigue and disease-specific QOL and PLB on breathlessness. There is also evidence that single studies on DB and YB has effect on disease-specific QOL. Few RCTs are available and the variable quality of the single RCTs in the SRs, seem to require more RCTs in particular for BCEs, but also RMT before conclusions regarding effects and high quality SRs can be written.

Background: International asthma treatment guidelines recommend tapering inhaled corticosteroid (ICS) therapy to the lowest dose that provides the maximum effect. Montelukast, a leukotriene receptor antagonist with complementary anti-inflammatory actions, has been shown in a tightly controlled trial to allow effective tapering of ICS therapy. Objectives: The purpose of this naturalistic study was to assess whether administration of montelukast could assist in the tapering of ICS therapy in patients with established asthma and whether the reduced dose achieved at 12 weeks could be maintained at 48 weeks without loss of asthma control. Methods: Patients with proven chronic asthma who were being treated with moderate to high doses of ICS (beclomethasone equivalent of 600 to 3200 μg/d) and required, according to their physician, the prescribed dose to maintain asthma control, were given open-label oral montelukast (10 mg/d at bedtime) for 48 weeks. Patients who were clinically stable, based on a composite clinical performance score, had their ICS dose reduced by ∼25% at 2-week intervals for 12 weeks and at 6-week intervals for the remaining 36 weeks. The percentage reduction in final ICS dose associated with clinical stability was the primary end point of the study. Results: Five hundred eighty-one patients were enrolled (57% female; mean age, 41 years). At 12 weeks, the mean ICS dose had been tapered by 82.3% (from 959 μg/d to 172 μg/d) and a total of 345 patients (59.5%) had completely stopped ICS. At 48 weeks, mean ICS dose had been tapered by 81.3% (from 959 μg/d to 178 μg/d; P P P Conclusion: In patients with chronic asthma treated with ICS, the addition of montelukast to assist in ICS tapering can be applied in clinical practice without loss of asthma control.

In a population survey on the south-western coast of Norway, 373 never smokers aged 18-73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1.0 1 min -1 , 80% of the subjects reached 1.5 1 min -1 and 50% of the subjects reached 2.0 1 min -1 . The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1.5 and 2.0 1 min -1 were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1.0 1 min -1 in women and 1.5 1 min -1 in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P

The aim was to examine the relationship of serum inflammatory markers to the level of single-breath diffusing capacity of carbon monoxide (TL,CO).A stratified sample (n=1,121) of a Norwegian general population aged 18–73 yrs was examined. The inflammatory markers measured were calprotectin, a prominent protein in the cytosol fraction of neutrophil granulocytes, and α1-antitrypsin (α1-AT), the major inhibitor of neutrophil elastase in the lower respiratory system. Both markers have increased circulating levels in the course of an acute inflammatory reaction.Subjects with a TL,CO1-AT (p=0.003) and calprotectin (pL,CO>100%. In multiple linear regression analyses, α1-AT was still significantly associated withTL,COafter adjusting for sex, age, smoking habits, haemoglobin, carboxyhaemoglobin, forced expiratory volume in one second and alveolar volume. In a similar analysis, no significant overall association was found between calprotectin and TL,CO, but in a stratified analysis, calprotectin was significantly related to TL,COin females. However, no significant sex interaction in the relationship between the inflammatory markers and TL,COwas found.The findings suggest that increased levels of α1-antitrypsin and of calprotectin are risk factors for decreased diffusing capacity of carbon monoxide.