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Rationale: The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives: To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes and to explore the possibility of using different LLN thresholds according to the pretest probability of disease. Methods: We studied the associations between prebronchodilator spirometric abnormalities (forced expiratory volume in the first second [FEV1] < LLN, forced vital capacity [FVC] < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30- to 46-year-old men who participated in a general population survey in Norway in 1988–1990 and were followed for 26 years. Analyses were performed with both local and Global Lung Function Initiative (GLI)-2012 reference equations, stratified by pretest risk (presence or absence of respiratory symptoms), and adjusted for age, body mass index, smoking, and education. Results: In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.15–1.95 for FEV1 < LLN) than those defined with Local-LLN5 in the general population (HR, 1.67; 95% CI, 1.50–1.87 for FEV1 < LLN) and symptomatic subjects (HR, 1.67; 95% CI, 1.46–1.91 for FEV1 < LLN). Overall, the prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10 and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions: There is a relationship between statistically based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations. [ABSTRACT FROM AUTHOR]

Introduction: Based on the National Lung Cancer Screening Trial (NLST), guidelines on screening programs for lung cancer have recommended low‐dose computed tomography (LDCT). De Torres et al made a score for COPD patients (COPD‐LUCSS) to improve their selection criteria. Objective: To examine and compare the discriminating value of both scores in a community‐based cohort of COPD patients. Methods: Four hundred and twenty‐two ever‐smokers with COPD from the GenKOLS study in Bergen were merged with the Cancer Registry of Norway. We divided the patients into groups of high and low risk according to the COPD‐LUCSS and the NLST criteria. Cox regression and logistic regression were used to analyse the associations between the scores and lung cancer. We used Harrell's C and area under the curve (AUC) to estimate discriminating values and to compare the models. Results: Hazard ratio for the high risk vs the low risk in the COPD‐LUCSS was 3.0 (1.4‐6.5 95% CI), P < 0.01. Hazard ratio for the NLST criteria was 2.2 (95% CI 1.1‐4.5), P < 0.05. Harrell's C was 0.63 for the COPD‐LUCSS and 0.59 for the NLST selection criteria. AUC was 0.61 for COPD‐LUCSS and 0.59 for NLST criteria. Comparing tests showed no differences (P = 0.76). Conclusion: Although the COPD‐LUCSS and the NLST criteria were associated with increased risk of lung cancer, the AUC and Harrell's C values showed that these models have poor discriminating abilities in our cohort of COPD patients. The COPD‐LUCSS was not significantly better than the NLST criteria. [ABSTRACT FROM AUTHOR]

Background: Previous studies, all of <20 years of followup, have suggested an association between lung function and the risk of fatal stroke. This study investigates the stability of this association in a cohort followed for 4 decades. Methods: The Bergen Clinical Blood Pressure Survey was conducted in Norway in 1964--1971. The risk of fatal stroke associated with forced expiratory volume after one second (FEV1) was estimated with Cox proportional hazards regression, making progressive adjustment for potential confounders. Results: Of 5617 (84%) participants with recorded baseline FEV1, 462 died from stroke over 152 786 subsequent person-years of follow-up according to mortality statistics of 2005; mean (SD) follow-up was 27 (12) years. An association between baseline FEV1 (L) and fatal stroke was observed; HR=1.38 (95% CI 1.11 to 1.71) and HR=1.62 (95% CI 1.22 to 2.15) for men and women, respectively (adjusted for age and height). The findings were not explained by smoking, hypertension, diabetes, atherosclerosis, socioeconomic status, obstructive lung disease, physical inactivity, cholesterol or body mass index and persisted in subgroups of never-smokers, subgroups without respiratory symptoms and survivors of the first 20 years of follow-up. For male survivors with a valid FEV1 at follow-up (1988--1990) (n=953), baseline FEV1 (L) indicated a possible strong and independent association to the risk of fatal stroke after adjustments for individual changes in FEV1 (ml/year) (HR 1.95 (95% CI 0.98 to 3.86)). Conclusion: There is a consistent, independent and long-lasting association between lung function and fatal stroke, probably irrespective of changes during adult life. [ABSTRACT FROM AUTHOR]

Atrial fibrillation ( AF) is the most common cardiac arrhythmia. The prevalence increases with increasing age. In middle-aged men, endurance sport practice is associated with increased risk of AF but there are few studies among elderly people. The aim of this study was to investigate the role of long-term endurance sport practice as a risk factor for AF in elderly men. A cross-sectional study compared 509 men aged 65-90 years who participated in a long-distance cross-country ski race with 1768 men aged 65-87 years from the general population. Long-term endurance sport practice was the main exposure. Self-reported AF and covariates were assessed by questionnaires. Risk differences ( RDs) for AF were estimated by using a linear regression model. After multivariable adjustment, a history of endurance sport practice gave an added risk for AF of 6.0 percent points (pp) (95% confidence interval 0.8-11.1). Light and moderate leisure-time physical activity during the last 12 months reduced the risk with 3.7 and 4.3 pp, respectively, but the RDs were not statistically significant. This study suggests that elderly men with a history of long-term endurance sport practice have an increased risk of AF compared with elderly men in the general population. [ABSTRACT FROM AUTHOR]

Few population-based studies are available on more than 5 years survival of lung cancer patients. The aims of this report were to study the survival and the predictors of survival in all lung cancer patients in a defined population and to determine whether and how the length of time from symptom onset to confirmed diagnosis (delay time) influenced survival. In a retrospective study, all incident cases from the Norwegian Cancer Registry and the hospital records in the Haugalandet area from 1990 to 1996 were followed until 31 December 2008. The dates of symptom onset, diagnosis, and death and information about demographics, initial stage, performance status, histology and initial symptoms were recorded. Of a total of 271 patients, 57 (21%) were women, and the mean age at diagnosis was 67.4 years. One-year survival was 29.2%, and five- and 10-year survival was 8.5% and 5.5%, respectively. The median (inter quartile range, IQR) survival time was 5.7 (1.9, 14.1) months and the median (IQR) delay time was 2.2 (1.1, 3.7) months. Twenty-five patients (10% of those who died) had a non-lung cancer cause of death. No weight loss at the time of diagnosis was a significant predictor for long survival in addition to younger age, limited stage, good functional performance and surgical treatment, but delay time for diagnosis had no effect on survival time for lung cancer. In the whole population of lung cancer patients, long-term survival remains poor and is not influenced by the diagnostic delay time. Please cite this paper as: Skaug K, Eide GE and Gulsvik A. Predictors of long-term survival of lung cancer patients in a Norwegian community. Clin Respir J 2011; 5: 50-58. [ABSTRACT FROM AUTHOR]

To determine the prevalence and predictors of undiagnosed chronic obstructive pulmonary disease (COPD) in Norway. An age and gender stratified random sample of all adults aged 47-48 and 71-73 years in Bergen, Norway, were invited. The 3506 participants filled in questionnaires including symptoms of COPD, smoking, socio-economic status, self-rated health and cardiac co-morbidity. Spirometry was performed before and after inhalation of 400 µg of salbutamol. COPD was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < 0.7 whereas diagnosed COPD was defined as having received treatment for obstructive lung disease the last year. Three hundred-three persons (9%) were classified as having COPD, and the undiagnosed fraction was 66%. In multiple logistic regression analysis, including multiple imputation, predictors of undiagnosed COPD were absence of COPD symptoms [odds ratio (OR) 6.92, P = 0.001], and self-report of being in good/excellent health (OR 2.39, P = 0.005). When post-bronchodilator FEV1 was added to the analysis, undiagnosed disease was predicted by pack years [OR 1.21 (1.01-1.47) per 10 pack-year increase, P = 0.043], and close to normal lung function [OR 1.48 (1.22-1.80) per 10% increase in post-bronchodilator FEV1 % predicted, P < 0.001]. Anthropometrical variables, socio-economic status and cardiac co-morbidity were not associated with having undiagnosed COPD. Two out of three COPD patients in Norway are undiagnosed. Risk factors for being undiagnosed are moderate reduction in lung function, absence of COPD symptoms and self-report of being in good health. Please cite this paper as: Hvidsten SC, Storesund L, Wentzel-Larsen T, Gulsvik A and Lehmann S. Prevalence and predictors of undiagnosed chronic obstructive pulmonary disease in a Norwegian adult general population. The Clinical Respiratory Journal 2009; DOI:10.1111/j.1752-699X.2009.00137.x. [ABSTRACT FROM AUTHOR]

The Bergen Clinical Blood Pressure Study in Norway was used to examine the relationship between body mass index (BMI (kg/m2)) and total mortality in different age segments. Of 6,811 invited subjects, 5,653 (84%) participated in the study (1965–1971) and 4,520 (66%) died during 182,798 person-years of follow-up (1965–2007). Mean age at baseline was 47.5 years; range 22–75 years. BMI (kg/m2) was calculated from standardized measurements of body height and weight and divided into four groups (<22.0, 22.0–24.9, 25.0–27.9, ≥28.0). The 20 years cumulative risk of death related to baseline BMI was U-shaped in the elderly (aged 65–75 years), whereas the pattern was more linear in the youngest age group (20–44 years). In contrast to the younger age groups, the highest mortality in the elderly was in the lower BMI range (<22.0 kg/m2) (adjusted Cox proportional Hazard Ratio 1.39, 95% Confidence Interval 1.10, 1.75) compared to the BMI reference group (22.0–24.9 kg/m2). This pattern persisted after 72 months of early follow-up exclusion and it was robust to adjustments for a wide range of possible confounders including gender, history of cardiovascular disease, respiratory disease or hypertension, smoking habits, physical activity, socioeconomic status, physical appearance and other anthropometric measures. The study shows that a low BMI is an appreciable independent risk factor of total mortality in the elderly, and not a result of subclinical disease or confounding factors such as current or previous smoking. Awareness of this issue ought to be emphasized in advice, care and treatment of elderly subjects. [ABSTRACT FROM AUTHOR]

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of a1-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the familybased International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family -based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the a-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48610210, rs8034191) and 5.74610210 (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The burden of diseases should be described in terms of costs. The available literature gives imprecise estimates of costs of chronic obstructive pulmonary disease (COPD) in the Nordic populations. Previous studies have methodological weaknesses related to choice of disease criteria, the use of highly selected populations and insufficient specification of the cost process. There are no robust estimates concerning the economics of COPD in Norway. Methods: We have conducted a 1 year follow-up cost of illness study in a general population, recruiting eversmoking Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2+ COPD patients and eversmokers without COPD. We have used diaries to recollect data, and comprehensive questionnaires to cover all costs of COPD. Results: The main challenges were the participants' unwillingness to complete diaries, the large amount of information and the logistics related to following up 476 individuals on four occasions during one year. Conclusions: We doubt the effect of diaries. However, we recommend a detailed planning of logistics and to emphasize main cost drivers. Please cite this paper as: Nielsen R, Klemmetsby M and Gulsvik A. Economics of COPD: literature review and experiences from field work. The Clinical Respiratory Journal 2008; 2: 104–110. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life. Methods: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%). Results: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined. Conclusion: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood. [ABSTRACT FROM AUTHOR]

The article examines all cases of lung cancer diagnosed from 1890 and 1996 in a defined hospital area in Norway. Pain, psychological symptoms and dyspnea were frequent complaints in the terminal phase in a community health service encompassing all lung cancer patients. Terminal dyspnea and nausea were associated with staging at the time of diagnosis, and terminal cough and nausea were associated with histology.

Background: As little is known about the long term relationship between respiratory symptoms and mortality from non-malignant respiratory diseases, a study was undertaken to investigate the predictive value of respiratory symptoms and symptom load for mortality from obstructive lung disease (OLD) and pneumonia in the long term in a Norwegian population. Methods: In 1972, 19 998 persons aged 15–70 years living in Oslo were randomly selected for a respiratory survey. The response rate was 89%. All were followed for 30 years. The association between cough, asthma-like symptoms, two levels of dyspnoea on exercise, a symptom score, and mortality from OLD and pneumonia were investigated separately for men and women by multivariable analyses, with adjustment for age, occupational exposure to air pollution, and smoking habits. Results: OLD accounted for 43% and pneumonia for 50% of all deaths from respiratory causes. In men the hazard ratio for mortality from OLD varied from 4.0 (95% confidence interval (CI) 2.4 to 6.5) for cough to 9.6 (95% CI 5.1 to 18.3) for severe dyspnoea, and in women from 5.1(95% CI 2.3 to 11 .3) for moderate dyspnoea to 13.0 (95% CI 6.0 to 28.3) for severe dyspnoea. The symptom score was strongly predictive of death from OLD in a dose-response manner. Conclusions: There is a significant, positive, strong association between respiratory symptoms and 30 year mortality from OLD. The association between respiratory symptoms and mortality from pneumonia is weaker and not significant. [ABSTRACT FROM AUTHOR]

Objective. We investigated the relationship between respiratory symptoms and mortality from all causes in a large Norwegian population. We also examined mortality during separate periods of follow-up. Design. Population-based, prospective cohort study. Setting and subjects. A total of 19 998 men and women were randomly selected from the general population of Oslo. They received a postal respiratory questionnaire. The response rate was 88%. Main outcome measures. The relationship between 11 respiratory symptoms and 30 years of total mortality was investigated separately for men and women by multivariate analyses with adjustment for age, smoking habits and occupational exposure to air pollution. Results. The relative mortality risk in comparison with asymptomatic subjects varied from 1.36 (95% confidence interval 1.25–1.48) for cough symptoms to 2.46 (2.13–2.85) for severe dyspnoea amongst men; the corresponding rates amongst women were 1.28 (1.16–1.40) and 1.52 (1.31–1.75), respectively. The relative risk of mortality in individuals with 1–3, 4–6 and 7 or more symptoms was 1.20, 1.60 and 2.53 ( P for trend 0.000) in men and 1.14, 1.47 and 1.84 ( P for trend 0.000) in women. Except for cough, the mortality rates associated with respiratory symptoms decreased significantly during follow-up. The positive association between respiratory symptoms and mortality was observed in people with and without cardiopulmonary diseases. Conclusions. Respiratory symptoms were significant predictors of mortality from all causes over 30 years, decreased during follow-up and were still increased after 30 years. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the effect of a poor indoor climate on the respiratory health of adults. No data are available regarding the contribution of indoor exposures to the burden of respiratory symptoms in the population. Methods: In 1996-7 a community sample of 3181 adults aged 26-82 years was invited to participate in a survey on indoor climate and respiratory health in Hordaland County, Norway. 2401 subjects agreed to take part. Logistic regression was used to examine the relationship between eight markers of indoor exposure and physician diagnosed asthma and five respiratory symptoms, after adjustment for sex, age, smoking, educational level, smoking habits, pack years, and occupational airborne exposure. Results: Mould exposure was associated with all the respiratory symptoms; the adjusted odds ratios (OR) varied from 1.6 (95% confidence interval (Cl) 1.0 to 2.4) for cough with phlegm to 2.3 (95% Cl 1.4 to 3.9) for grade 2 dyspnoea. Keeping a cat or dog in childhood was associated with grade 2 dyspnoea and attacks of dyspnoea, with adjusted ORs of 1.3 (95% Cl 1.0 to 1.7) and 1.4 (95% Cl 1.1 to 1.8), respectively. Having a fitted carpet in the bedroom was negatively associated with three of the five respiratory symptoms. 3-5% of the frequency of the respiratory symptoms in the study population could be attributed to exposure to visible moulds. Conclusion: Mould exposure is an independent risk factor for several respiratory symptoms in a general population covering a wide age span, but it makes only a small contribution to the respiratory symptom burden in the population at large. [ABSTRACT FROM AUTHOR]

Achieving a high response rate is often expensive and time consuming. Does an extensive survey effort change prevalence estimates and exposure-disease relations? In 1998–1999, the authors conducted a population-based respiratory health survey in two Norwegian counties (Oslo, n = 20,000; Hordaland, n = 5,000) of a random sample of the adult population aged 15–70 years. A postal questionnaire was mailed, with as many as two reminder letters. A 25% random sample of postal nonresponders was contacted by ordinary or cellular telephone. Cumulative response rates after the first mailing, first reminder, second reminder, and telephone follow-up were 42.7%, 60.7%, 68.3%, and 79.9%, respectively. Compared with initial postal responders, responders at later stages were younger, and more were male. Late responders had a lower educational level, were more often smokers, and were occupationally exposed to dusts or gases more frequently. After the authors adjusted for these factors, late responders were found to have less asthma, attacks of breathlessness, and hay fever. Hardly any changes in prevalences and odds ratios were noted when initial responders were compared with all responders. The additional contribution of sending reminder letters and conducting a telephone follow-up to prevalence estimates and the exposure-disease relation was small. A single letter would have produced nearly the same prevalence estimates and risk factor associations. [ABSTRACT FROM PUBLISHER]

Little is known about the comparability of postal and telephone survey modes in epidemiology. A cross-sectional, population-based study (n = 25,000) of lung disease was performed in 1998-1999 in two regions of Norway. Initial surveying was done by postal questionnaire. A 1% random sample (n = 171) of previous postal responders were resurveyed by telephone or cellular contact. The response rate was 67% on the telephone/cellular interview. Fewer incomplete answers were given by telephone than by mail. A lower prevalence was found by telephone for morning cough and exposure to passive smoking at work or home. Reproducibility was high for asthma, hay fever, wheezing, and attacks of breathlessness. Moderate reproducibility was seen for symptoms of chronic bronchitis. Reproducibility was low for indoor and work environment, although it was high for early life factors. Concordance coefficients were high for all continuous measures such as height, body weight, and pack-years. The authors conclude that the comparability between the postal and the telephone survey modes was good. The telephone survey mode gave more complete information. Survey mode may have a moderate effect on study results, depending on the specific questions asked. Am J Epidemiol 2002;155:572-6. [ABSTRACT FROM AUTHOR]

The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south-western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one-second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one-second forced inspiratory volume (FIV1). The within-subject variation increased with body height and was considerably larger for FIV1 than for FVC, FEV1 or FIVC. A four-parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close-to-normal distribution, and the fifth-percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population. [ABSTRACT FROM AUTHOR]

This study assessed associations of three theoretically different occupational class schemes with all-cause and cardiovascular mortality in Norwegian men and women. Pooled survey and register data from four Norwegian cohort studies. We pooled survey data from four general population cohorts (N = 97,469) linked to national mortality registries with follow-up over 45 years. Survival was modelled using accelerated failure time models stratified by sex for three class schemes: The European Socio-Economic Classification (ESeC), The Oslo Register Data Class scheme (ORDC) and The International Socio-Economic Index (ISEI). Main analyses were adjusted for age, birth cohort, and study. Secondary analyses included smoking behaviour as a mediator. During median 27.6 years of observation, 37,488 participants had died (13,243 from cardiovascular disease). Hazard ratios for male all-cause mortality were lowest in the highest occupational class categories ORDC 2: 0.68 (0.65–0.72), ESeC 1: 0.76 (0.73–0.79) and ISEI 5th quintile: 0.80 (0.77–0.82) compared to working class reference categories. Female mortality risks were lowest for Cultural Lower Middle class ORDC 7: 0.84 (0.72–0.98), Small Employers and Self-employed ESeC4: 0.70 (0.50–0.97) and ISEI 5th quintile: 0.79 (0.70–0.90). Patterns for cardiovascular mortality were similar to all-cause mortality. Including smoking behaviour as a mediator attenuated associations, but overall mortality patterns according to occupational class remained unchanged. The results underline that mortality inequalities do not simply consist of higher risks in the most disadvantaged groups. The association of occupational class with mortality is found across different categories of occupational class schemes, illustrating their continued relevance for studying social determinants of health. [ABSTRACT FROM AUTHOR]

We examined the effects from subjects, technicians and spirometers on within-session variability in successful recordings of forced expiratory volume in 1 second (FEV1 ) and forced vital capacity (FVC) in 4989 asymptomatic never-smoking men. All eligible men aged 30–46 years living in western Norway (n = 45 380) were invited to a cross-sectional community survey. Information on respiratory symptoms, smoking habits and occupational exposures was obtained from a self-administered questionnaire. Three successful FEV1 and FVC recordings were obtained in 26 368 attendants using three dry-wedge bellow spirometers operated by 10 different technicians. Within-subject standard deviation (SD) from three recordings of FEV1 and FVC was on average 102 and 106 ml, respectively, and increased with height (14 and 17 ml, respectively, per 10 cm) and body mass index (BMI) (11 and 14 ml, respectively, per 5 kg m-2 ). Between-subject SD of the mean of three FEV1 and FVC recordings was 591 and 754 ml, respectively, and increased in groups of increasing height (43 and 40 ml, respectively, per 10 cm). Small, but significant, differences were observed between technicians in within-subject SD and in levels of FEV1 and FVC. Homogeneity of between-subject variability, necessary for linear regression analysis, was obtained using FEV1 and FVC divided by height squared. In conclusion, within-subject variability in three successful spirometric recordings was small, but dependent on height and BMI of the subjects as well as technician performance. The observed heterogeneity in between-subject variation in FEV1 and FVC levels disappeared when each variable was divided by height squared. Novel multiple linear regression equations for FEV1 /height2 and FVC/height2 were developed to be used in evaluating the effects from occupational airborne exposures in... [ABSTRACT FROM AUTHOR]

Objectives: To identify, in this general population study, predictors of spirometric test failure on the 1983 and 1993 acceptability criteria from the European Community for Coal and Steel (ECCS).Methods: All men aged 30-46 years living in western Norway (n = 45,380) were invited to join a cross sectional community survey. Respiratory symptoms, smoking habits, and marital status were found from self administered questionnaires, and measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were performed with dry wedge bellow spirometers.Results: Altogether 29,611 subjects (65%) participated in this survey. Spirometric recordings were obtained in 26,803 of these (91%) of whom 1.6% failed the 1983 criterion (< or = 300 ml between the two highest FVC values) and 9.5% failed the 1993 criteria (< or = 5% or 100 ml between the two highest FEV1 and the two highest FVC values). Spirometric failures on both criteria were more prevalent in never smokers, single men, and subjects with respiratory symptoms than in ever smokers, married, and asymptomatic subjects. Failure of the 1993 criteria increased with age and declining height. Morning cough and phlegm, breathlessness uphill, attacks of breathlessness, and wheezing were related to failure of the 1993 criteria after adjustment for demographic variables and smoking, whereas only breathlessness uphill was related to failure of the 1983 criterion.Conclusions: In men aged 30-46 years, spirometric test failures on both the 1983 and 1993 ECCS acceptability criteria occurred more often in never smokers than in smokers and ex-smokers after adjustment for other covariables. Spirometric test failure with the 1993 criteria also varied with height and most respiratory symptoms. The higher failure rates found in non-smokers, in shorter, and in single men could be due to late compression of the airways, smaller lung volumes, and poor general health, respectively. [ABSTRACT FROM AUTHOR]

Background: The importance of occupational exposure to airborne agents in the development of obstructive disease is uncertain. Studying the relation in a community population has the benefit of reducing the healthy worker effect seen in studies of working populations.Methods: The prevalence of obstructive lung disease was examined in a Norwegian general population aged 18-73 in a two phased cross sectional survey. In the second phase a stratified sample (n = 1512) of those responding in the first phase was invited for clinical and spirometric examination (attendance rate 84%). Attenders were asked to state all jobs lasting greater than 6 months since leaving school and to say whether they had been exposed to any of seven specific agents and work processes potentially harmful to the lungs.Results: The prevalence of asthma and chronic obstructive lung disease was 2.4% and 5.4%, respectively; spirometric airflow limitation (FEV1/FVC less than 0.7 and FEV1 less than 80% of predicted values) was observed in 4.5% of the population. All jobs were categorised into three groups according to the degree of potential airborne exposure. Having a job with a high degree of airborne exposure increased the sex, age, and smoking adjusted odds ratio for obstructive lung disease (asthma and chronic obstructive lung disease) by 3.6 (95% confidence interval 1.3 to 9.9) compared with having a job without airborne exposure; the association with spirometric airflow limitation was 1.4 (0.3 to 5.2). Occupational exposures to quartz, metal gases, aluminium production and processing, and welding were significantly associated with obstructive lung disease after adjusting for sex, age, and smoking habit, the adjusted odds ratios varying between 2.3 and 2.7. Occupational exposure to quartz and asbestos was significantly related to spirometric airflow limitation in people older than 50.Conclusion: Occupational title and exposure to specific agents and work processes may be independent markers of obstructive lung disease in the general population. [ABSTRACT FROM AUTHOR]

Aims: Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by multiple genetic and environmental factors. This short communication gives a description of the preliminary genetic results from a case-control study in Bergen, Norway. Methods: A large case-control study in Bergen in 2003–2005 with 6365 invited subjects generated 1954 cases or controls. The overall attendance of invited subjects was 60%, but causes of non-attendance varied considerably among different sources of recruitment. Results: In this case-control study, the candidate gene SERPINE2 on chromosome 2q has demonstrated significant association to COPD. However, only weak or lacking associations have so far been observed for the other candidate genes examined. Conclusion: These findings provide support for SERPINE2 as a COPD susceptibility gene in the Norwegian population. Please cite this paper as: Sørheim I-C and Gulsvik A. Genetics of chronic obstructive pulmonary disease in Bergen, Norway: a case–control study. The Clinical Respiratory Journal 2008; 2: 129–131. [ABSTRACT FROM AUTHOR]

Background: Evidence from several studies show poor guideline adherence to COPD treatment, but no such study has been undertaken in Norway. The objectives of this study, was to estimate and compare the guideline adherence to COPD treatment in general population-based and hospital-recruited COPD patients, and find possible predictors of guideline adherence.Methods: From the prospective, observational EconCOPD-study, we analysed guideline adherence for 90 population-based COPD cases compared to 245 hospital-recruited COPD patients. Overall guideline adherence was defined as correct pharmacological treatment, and influenza vaccination the preceding year, and having received smoking cessation advice. Multivariate logistic regression analysis was performed with the dichotomous outcome overall guideline adherence adjusting for relevant variables.Results: The overall guideline adherence for population-based COPD cases was 6.7%, significantly lower than the 29.8% overall guideline-adherence amongst hospital-recruited COPD patients. Adherence to pharmacological treatment guidelines was 10.0 and 35.5%, for the two recruitment sources, respectively. GOLD-stage 3 to 4 was associated with significantly better guideline adherence compared to GOLD-stage 2 (OR (95% CI) 18.9 (8.37,42.7)). The unadjusted difference between the two recruitment sources was completely explained by degree of airflow obstruction.Conclusion: Overall guideline adherence was very low for both recruitment sources. We call for increased attention from authorities and healthcare personnel to improve the quality of care given to this patient group. [ABSTRACT FROM AUTHOR]

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RN reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from Boehringer Ingelheim, outside the submitted work. All other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: This study assessed the association between respiratory symptoms and mortality in four cohorts of the general population in Norway aged 15-75 years and in selected subgroups in the pooled sample., Methods: The study comprised 158,702 persons, who were drawn randomly from the Norwegian population register. All subjects received a standardized, self-administered questionnaire on 11 respiratory symptoms between 1972 and 1998, with follow-up of death until December 31, 2017. Analyses were performed on 114,380 respondents., Results: The hazard of death was closely associated with sex, age, and education. The hazard ratios (HR) for death and the 95% confidence intervals (CI) by risk factors were similar in the four cohorts. After adjustment for demographic and environmental, modifiable factors, the HR for death was 1.90 (95% CI 1.80-2.00) for breathlessness score 3, 1.28 (1.21-1.37) for cough/phlegm score 5 and 1.09 (1.05-1.14) for attack of breathlessness/wheeze score 2 compared to the referent (no symptom), respectively. The cough/phlegm score was associated with death in current smokers but not in never smokers or ex-smokers. Breathlessness score was associated with death in men and women., Conclusion: Among persons aged 45-75 years, respiratory symptoms were significant predictors of all cause mortality. Education and smoking habits influenced only the associations between coughing and mortality. The associations were independent of study sites., (Copyright © 2020. Published by Elsevier Ltd.)

Rationale: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 is based on an ABCD assessment tool of symptoms and exacerbation history and grade 1-4 of airflow limitation severity, facilitating classification either into 4 groups (ABCD) or 16 groups (1A-4D). We aimed to compare the GOLD 2011, GOLD 2017 ABCD, and GOLD 2017 1A-4D classifications in terms of their distribution and prediction of mortality and hospitalizations., Methods: In the GenKOLS study, 912 COPD patients with FEV1 less than 80% of the predicted answered questionnaires and performed lung function testing in 2003-2005. The patients were recruited from a hospital patient registry (n=662) and from the general population (n=250), followed up until 2011 with respect to all-cause and respiratory mortality, and all-cause and respiratory hospitalizations. We performed logistic regression and receiver operating curve (ROC) analyses for the different classifications with estimations of area under the curve (AUC) for comparisons., Results: Mean age at baseline was 60 years (SD 11), 55% were male. Mean duration of follow-up was 91 months. By GOLD 2011, 21% were classified as group A, 29% group B, 6% group C, and 43% as group D, corresponding percentages for GOLD 2017 were: 25%, 52%, 3%, and 20%. The GOLD 2011 classification had higher AUC values than the GOLD 2017 group ABCD classification for respiratory mortality and hospitalization, but after inclusion of airflow limitation severity in GOLD 2017 groups 2A-4D, AUC values were significantly higher with GOLD 2017., Conclusion: In a clinically relevant sample of COPD patients, the GOLD 2017 classification doubles the prevalence of group B and halves the prevalence of groups C and D as compared to the GOLD 2011 classification. The prediction of respiratory mortality and respiratory hospitalization was better for GOLD 2017 2A-4D taking airflow limitation severity into account, as compared to GOLD 2017 ABCD and GOLD 2011., Competing Interests: Professor Jon Hardie reports personal fees from AstraZeneca, outside the submitted work. Dr Odd Erik Johansen is an employee of Boehringer Ingelheim. The authors report no other conflicts of interest in this work.

The predictors of autopsy and the accuracy of European short list (E) codes of respiratory diseases lack recent knowledge. A 10% random sample (n=6811) of inhabitants of Bergen, Norway, aged 20-70 years, was invited to participate in a survey in 1965-1971 (participation rate 83%). By December 31, 2005, 4387 (64%) participants had died and 1163 (27% of the deceased) had been given an autopsy. Causes of death were tuberculosis (E02, 0.2%), lung malignancy (E15, 3.5%), influenza (E38, 0.2%), pneumonia (E39, 6.5%) and chronic lower respiratory diseases (E40, 3.2%). Male sex, early deaths in the surveillance period and E15 were positive predictors of an autopsy examination, whereas old age and E39 were strong negative predictors. Among those referred for a post mortem examination, the cause of death was verified as tuberculosis in 0.3%, lung cancer in 8.1%, acute pneumonia in 2.0% and chronic obstructive lung diseases in 4.9%. Cohen's kappa coefficients (E codes versus autopsy) were 0.91 (95% CI 0.86-0.96) for E15, 0.37 (95% CI 0.20-0.54) for E39 and 0.65 (95% CI 0.54-0.76) for E40. These findings matter when deaths from respiratory diseases are used as end-points in epidemiological association studies and clinical trials., (Copyright ©ERS 2015.)

Background: Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population., Methods: We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis., Results: For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7)., Conclusions: We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD., Trial Registration: ClinicalTrials.gov NCT00608764, NCT00292552.

Background: Prevalence of COPD is increasing worldwide, and there is need for regularly updated estimates of COPD prevalence and risk factors., Methods: In the Norwegian Hordaland County Cohort Study (HCCS), 1664 subjects aged 35-90 yrs answered questionnaires and performed spirometry in 2003-05. We estimated COPD prevalence and analysed risk factors for COPD with logistic regression., Results: In a previous study phase, prevalence of GOLD-defined COPD was 7%. Eight years later, corresponding prevalence was 14%. Seventy % of the subjects experienced respiratory symptoms. Only 1 out of 4 had a physician's diagnosis. Significant risk factors for COPD were sex, age, smoking habits and pack-years. Men had 1.7 (OR, 95% CI 1.2, 2.3) higher odds for COPD than women. Subjects above 65 yrs had 10.3 (OR, 95% CI 6.4, 16.5) times higher odds for COPD than subjects below 40 yrs. Heavy smokers had 4.2 (OR, 95% CI 2.6, 6.7) times higher odds for COPD than subjects with <10 pack-years. When compared with the previous study phase, age and smoking status had roughly the same associations with COPD prevalence. Educational level and male gender, on the other hand, had less effect on COPD prevalence in 2005 than in 1997, while pack years were more important in 2005 than in 1997., Conclusions: Prevalence of GOLD defined COPD has increased from 7% to 14% in nine years. Although the risk factors remain the same, the strength of associations vary. There is still substantial under diagnosis in COPD, and better disease awareness and diagnostic routines are needed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV(1)); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity., Methods: The relationship between FEV(1) and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects., Results: Non-linear relationships between smoking and FEV(1) were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV(1) is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case-Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV(1) analysis, p=0.01 for COPD susceptibility analysis)., Conclusion: In study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV(1) is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.

Mortality statistics represent important endpoints in epidemiological studies. The diagnostic validity of cerebral stroke and ischemic heart disease recorded as the underlying cause of death in Norwegian mortality statistics was assessed by using mortality data of participants in the Bergen Clinical Blood Pressure Study in Norway and autopsy records from the Gade Institute in Bergen. In the 41 years of the study (1965-2005) 4,387 subjects had died and 1,140 (26%) had undergone a post mortem examination; 548 (12%) died from cerebral stroke and 1,120 (24%) from ischemic heart disease according to the mortality statistics, compared to 113 (10%) strokes and 323 (28%) coronary events registered in the autopsy records. The sensitivity and positive predictive value of fatal cerebral strokes in the mortality statistics were 0.75, 95% confidence interval (CI) [0.66, 0.83] and 0.86 [0.77, 0.92], respectively, whereas those of coronary deaths were 0.87 [0.84, 0.91] and 0.85 [0.81, 0.89] respectively. Cohen's Kappa coefficients were 0.78 [0.72, 0.84] for stroke and 0.80 [0.76, 0.84] for coronary deaths. In addition to female gender and increasing age at death, cerebral stroke was a negative predictor of an autopsy being carried out (odds ratio (OR) 0.69, 95% CI [0.54, 0.87]), whereas death from coronary heart disease was not (OR 1.14, 95% CI [0.97, 1,33]), both adjusted for gender and age at death. There was substantial agreement between mortality statistics and autopsy findings for both fatal strokes and coronary deaths. Selection for post mortem examinations was associated with age, gender and cause of death.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Background: Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain., Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease., Results: PI MZ was associated with a 3.5% lower FEV₁/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV₁/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies., Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV₁/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.

Background: The number of female smokers developing chronic obstructive pulmonary disease (COPD) is rapidly increasing, but whether or not there exists a differential susceptibility by gender remains controversial., Methods: How smoking behaviour and subsequent lung function reduction differed by gender was examined in a study including 954 subjects with COPD and 955 subjects without COPD. The study focused on two subgroups: subjects with COPD <60 years of age (early-onset group, n=316) and subjects with COPD with <20 pack-years of smoking (low exposure group, n=241)., Results: In the low exposure group, female subjects with COPD had lower forced expiratory volume in 1 s (FEV(1)) % predicted (48.7% vs 55.8%, p=0.001) and more severe disease (50.4% vs 35.6%, p=0.020, in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 3 and 4) than male subjects with COPD. Females also had lower FEV(1)% predicted (50.6% vs 56.0%, p=0.006) and more severe COPD (41.7% vs 31.1% in GOLD stage 3 and 4, p=0.050) in the early-onset group. Using multivariate regression, female gender was associated with 5.7% lower FEV(1)% predicted in the low exposure group (p=0.012) and a similar trend was observed in the early-onset group (p=0.057). The number of pack-years was not significantly associated with lung function in female subjects with COPD in this study, and the dose-response relationship between smoking and lung function differed by gender at lower levels of smoking exposure. Interaction analysis suggested that the effect of smoking on lung function might be different by gender (p=0.027 in all subjects with COPD)., Conclusions: Female gender was associated with lung function reduction and more severe disease in subjects with COPD with early onset of disease or low smoking exposure. The findings may suggest a gender difference in susceptibility to the lung-damaging effects of cigarette smoking, but alternative explanations should be considered.

Introduction: Sampling is regarded as crucial to the validity of case-control studies. Ideally, cases and controls should be selected from the same source population, but deviations from this approach are often seen., Objective: Our objective was to examine how exposure-disease relationships in a study on chronic obstructive pulmonary disease (COPD) were affected by the sampling sources of cases and controls., Methods: A Norwegian case-control study on COPD including 1909 subjects used three sources of recruitment for cases (general population, hospital registry and volunteers) and two sources for controls (general population and volunteers). This resulted in six sampling combinations of cases and controls (groups A-F). We examined how the risk factors gender, age, smoking, educational level and comorbidity were associated with COPD in these six sampling groups., Results: Several exposure-disease associations were dependent on variation in sampling source, thereby demonstrating the possibility of selection bias. The theoretically most ideal sampling group is likely group A, where both cases and controls are recruited from a general population. When using group A as a reference, the groups containing either voluntary controls and/or hospital-based cases deviated the most, suggesting higher susceptibility to selection bias in these groups., Conclusion: Recruitment from several sources made our study design vulnerable to selection bias. Our findings should bring about increased awareness to the sampling process, and encourage sampling of cases and controls from the same source population in future studies.

Background: Little is known concerning the hospitalisation of all lung cancer patients in a geographically defined population., Method: All incident lung cancer patients in the Haugalandet area in South-west Norway from 1990 through 1996 were followed from diagnosis till either death or end of follow-up 1 December 2003. Initial symptoms, anatomical stage, functional performance status, histology, initial treatment, terminal care, number of admissions as well as days of hospitalisation were recorded., Results: Of a total of 271 patients (57 women) only 16 were still alive at end of follow-up. Median survival time was 170 days. Mean age at the first admission was 67.4 years (range 21-89 years). Median number (inter quartile range) of admissions was 3 (2, 5) and total hospitalisation days 35 (18, 58). Altogether 26% of the days in institutional care were spent in nursing homes. The 31 patients surgically treated had the highest number of hospitalisation days: 75 (56, 96). Young age, low anatomical stage and good performance status at time of diagnosis were associated with increased use of hospitalisation days. Cox regression analysis showed that treatment interventions and dyspnoea were significant predictors when adjusting for age, tumour stage and performance status., Conclusion: In a population-based cohort of incident lung cancer patients, days in health care institutions involved a large part (19%) of all survival time for those who died. However, the absolute number was greater for those with small tumours and high functional performance status which initiated other interventions than palliative treatment.

The Burden of Obstructive Lung Disease (BOLD) initiative provides standardised estimates of the burden of chronic obstructive pulmonary disease (COPD) worldwide. We estimate the current and future economic burden of COPD in Reykjavik, Iceland and Bergen, Norway using data from the BOLD initiative. Data on utilisation of healthcare resources were gathered from the BOLD survey, existing literature and unit costs from national sources. Economic data were applied to a Markov model using transition probabilities derived from Framingham data. Sensitivity analyses were conducted varying unit costs, utilisation and prevalence of disease. The cost of COPD was 478 euro per patient per yr in Iceland and 284 euro per patient per yr in Norway. The estimated cumulative costs of COPD for the population aged > or = 40 yrs, were 130 million euro and 1,539 million euro for the following 10 yrs in Iceland and Norway, respectively. Costs of COPD accounted for 1.2 and 0.7% of healthcare budgets in Iceland and Norway, respectively. Sensitivity analyses showed estimates were most sensitive to changes in exacerbation frequency. COPD has a significant economic burden in both Iceland and Norway and will grow in the future. Interventions aimed at avoiding exacerbations will have the most impact on costs of COPD over the next 20 yrs.

Chronic obstructive pulmonary disease (COPD) is characterized by airway epithelial damage, bronchoconstriction, parenchymal destruction and mucus hypersecretion. Upon activation by a broad range of stimuli, transient receptor potential vanilloid 4 (TRPV4) functions to control airway epithelial cell volume and epithelial and endothelial permeability; it also triggers bronchial smooth muscle contraction and participates in autoregulation of mucociliary transport. These functions of TRPV4 may be important for the regulation of COPD pathogenesis, so TRPV4 is a candidate gene for COPD. We genotyped 20 single nucleotide polymorphisms (SNPs) in TRPV4, and tested qualitative COPD and quantitative FEV(1) and FEV(1)/(F)VC phenotypes in two independent large populations. The family population had 606 pedigrees including 1891 individuals, and the case-control sample included 953 COPD cases and 956 controls. Family-based association tests were performed in the family data. Logistic regression and linear models were used in the case-control data to replicate the association results. In the family data, seven out of 20 SNPs tested were associated with COPD (2.5 x 10(-4) < or = P < or = 0.04) and six SNPs were associated with FEV(1)/VC (0.02 < or = P < or = 0.03) from family-based association tests (PBAT) analysis. Four out of the seven SNPs associated with COPD demonstrated replicated associations with the same effect directions in the case-control population (0.02 < or = P < or = 0.03). Significant haplotype associations supported the results of single SNP analyses. Thus, polymorphisms in the TRPV4 gene are associated with COPD.

Background: Little is known concerning the precision of self-reported health economic data., Aim: To investigate the repeatability of self-reported health economic cost and utilization data in subjects with chronic obstructive pulmonary disease (COPD)., Methods: Twelve weeks after inclusion, a physician and a nurse in random order interviewed 29 subjects with post-bronchodilator COPD included from a research registry of COPD patients. The interview recorded healthcare utilization and costs, sick leave, exacerbations and quality of life (QoL). Variation of individual agreement of observations was described estimating kappa statistics and 95% limits of agreement., Results: Mean age was 63 years (standard deviation (SD) 10) and 17 participants were men. Average FEV(1)% predicted was 56% (SD 15). For sick leave, exacerbation, healthcare provider visit, change of medication, assistance and leisure time the kappa values were 1.00, 0.73, 0.73, 0.66, 0.63 and 0.54, respectively. The physician recorded fewer days of exacerbation and fewer contacts with healthcare providers than the nurse (p=0.01 and p=0.05, respectively). The 95% limits of agreement for costs of drugs were -690 to +710 Norwegian Kroner (NOK), -1200 to +899 NOK for costs of healthcare providers and -20 to +26 for QoL as measured by a visual analogue scale., Conclusion: Repeatability of economic data from COPD patients showed considerable variation. This issue should be addressed when analyzing cost data from interviews and when designing studies on health economy.

Background: Our aim was to investigate the association between respiratory symptoms and mortality from ischaemic heart disease (IHD) and stroke in a population during 30 years follow-up., Methods: In 1972, 19998 persons aged 15-70 years, living in Oslo, were selected for a respiratory survey (response 89%). Respiratory symptoms were divided into four groups and given a score. The association between respiratory symptoms and mortality from IHD and stroke were investigated separately for men and women, with adjustment for age, occupational exposure to air pollution and smoking habits., Results: IHD accounted for 1572 and stroke for 653 of all deaths. The adjusted hazard ratio (HR) for mortality from IHD in men varied from 1.3 (95% confidence interval, 1.1-1.5) to 3.0 (2.3-3.8) and in women from 1.2 (1.0-1.5) to 1.9 (1.4-2.5) for cough symptoms and severe dyspnoea, respectively. Symptom score predicted death from IHD, in a dose-response manner. The HR for mortality from stroke varied from 1.0 to 2.3 in men and from 1.1 to 1.5 in women for the symptom groups, but was significant only among men reporting severe dyspnoea and among women reporting moderate dyspnoea. For all respiratory symptoms, the excess risk for cardiovascular mortality decreased during follow-up, but IHD-mortality was still significantly increased the last decade., Conclusion: We found a significant, positive association between respiratory symptoms and 30-year mortality from IHD. The positive association was weaker between respiratory symptoms and long-term mortality from stroke.

Background: Few publications are available on how salaries are established for physicians with science as their main occupation. The results of a questionnaire survey to medical doctors are reported., Material and Methods: A questionnaire was sent to members of The Norwegian Medical Association's branch for doctors in academic medicine in spring 2005. Questions concerned how they thought scientific qualifications and production affected their present salary and what they considered to be a reasonable salary for a researcher with their qualifications and production. 304 of 487 (62%) doctors answered., Results: The study included 128 full-time professors, 101 associate professors or post-doctoral scientists with a PhD, 44 scientists without a PhD and 31 PhD-students. The average age was 52 years, and 28% were women. 71% had a university as their main employer. The median number of peer-reviewed scientific publications was 19 per physician-scientist for the last 5 years. The average annual salary was 498,000 NOK, and the average increase in salary considered to be reasonable was 279,000 NOK. A reasonable salary for evaluating a PhD-thesis was considered to be 18,700 NOK and that for giving a 45-minute lecture was 3,200 NOK. In a multiple linear regression analysis on actual salary, the significant predictors were employer, scientific qualifications, age, and sex. Predictors for the difference between reasonable and actual salary was scientific production and employer. Age, employer or scientific qualifications could not predict who considered a doubling of the present salary (for a 45-minute lecture and evaluating a PhD) to be appropriate., Interpretation: Universities should be aware of the large gap between salaries to physician-scientists employed by universities and to those employed by other institutions. Scientific production should be more emphasized in future negotiations on salaries.

Background: For a number of chronic diseases, health-related quality of life (HRQoL) has become an important outcome measure. Little data are available on how incidence, remission, or persistence of respiratory symptoms affect HRQoL., Methods: The Hordaland County Cohort Study was conducted between 1985 and 1997, and comprised 3,786 subjects, randomly selected, and aged 15 to 70 years in 1985. Respiratory symptoms were assessed both in 1985 and 1996/1997, and HRQoL was measured by the Short-Form 12 questionnaire in 1996/1997. Robust linear regression analysis was used to examine the relationship between changes in six respiratory symptoms and the physical component score (PCS) and mental component score (MCS)., Results: Among subjects with incidence or persistence of any of the six examined respiratory symptoms, PCS and MCS were significantly lower than among subjects without symptoms. The PCS was more reduced than the MCS in symptomatic subjects; however, this trend was reduced after adjustment for the confounder's gender, age, educational level, body mass index, and smoking status. Dyspnea attacks and dyspnea grade 2 had the largest negative impact on both PCS and MCS., Conclusions: This is the first longitudinal population study to show the negative impact of incidence and persistence of respiratory symptoms on HRQoL.

Normative cut-off values for the bronchodilator reversibility test are published neglecting factors that may influence the test result other than disease. The objective of this cross-sectional study of a general population was to examine how a salbutamol reversibility test response is depending on anthropometrical variables and smoking. An age and gender stratified random sample of all adults aged 47-48 and 71-73 years living in Bergen, Norway, was invited. The 3506 attendants (69%) filled in a questionnaire and performed spirometry before and after inhalation of 400 microg salbutamol. The mean (SD) absolute FEV(1) bronchodilator response, the change in % predicted, and the change in % initial among middle-aged were 71 (122) ml, 2.0 (3.3)%, and 2.4 (4.1)%, and in the elderly 64 (113) ml, 2.4 (4.3)% and 3.3 (5.9)%, respectively. In a multiple linear regression analysis including adjustment for the initial FEV1 in % predicted, smoking and pack-years were negatively correlated to all indices. Current smoking was considerably more important than past smoking. Female gender, old age, and BMI were positively correlated with the percentage change indices, but the correlation with BMI decreased with increasing heights. These trends were unchanged after excluding subjects with obstructive lung disease or coronary heart disease. This study demonstrates that smoking habits predict all indices expressing the salbutamol bronchodilator response among middle-aged and elderly from a general population. Also, the change in % predicted and the change in % initial indices are dependent on anthropometrical variables. However, although smoking and anthropometrical variables, as well as level of lung function predict the response to inhaled beta2-agonists, these factors explain only 7-16% of the total variation of the measurement indices, and seem therefore of minor importance to the interpretation of the test result.

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

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

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.