Self-reported influenza vaccination and protective serum antibody titers in a cohort of COPD patients.

BACKGROUND: COPD patients are advised vaccination against seasonal influenza, yet few studies have evaluated the protective antibody titers obtained in this patient group. AIMS: 1) To describe protective titers in COPD patients who self-reported influenza vaccination compared with vaccinated subjects without COPD and unvaccinated COPD patients, 2) analyze whether clinical parameters predicted influenza-specific antibody titers, and 3) whether antibody titers to influenza A at baseline could predict exacerbation risk or 5 years all-cause mortality. METHODS: Influenza A (H1N1 and H3N2) titers were measured by haemagglutination inhibition assay in serum from 432 COPD patients and 77 controls in the Bergen COPD Cohort Study, at yearly visits between 2006/09. Titers of 40 or above were considered protective. We examined the variables sex, age, body composition, smoking, GOLD stage, yearly exacerbations, inhaled steroids, and Charlson score as predictive of titers, both univariately and in a multivariable model estimated by generalized estimating equations. The exacerbation incidence rate ratios and mortality hazard ratios were assessed by negative binominal and cox regression models respectively. RESULTS: At baseline, 59% of COPD patients reported influenza vaccination during the last season. Levels of predictive titers varied considerably each season, but trended lower in COPD patients compared with controls. Neither sex, age, body composition, smoking, comorbidities, GOLD stage nor use of inhaled steroids consistently predicted titers. Having high titers at baseline did not impact later risk for exacerbations, but seemed to be associated with higher all-cause mortality, even after adjustment for COPD disease characteristics. CONCLUSION: Vaccination coverage for influenza is imperfect for COPD patients in Norway, and there is a concern that immunization is suboptimal.

Predictors for PaO2 and hypoxemic respiratory failure in COPD-A three-year follow-up.

BACKGROUND: Knowledge about predictors for developing hypoxemia in the course of chronic obstructive pulmonary disease (COPD) progression is limited. The objective of the present study was to investigate predictors for overall PaO2, for a potential change in PaO2 over time, and for first occurrence of hypoxemia. METHODS: 419 patients aged 40-76 years with COPD GOLD stages II-IV underwent clinical and pulmonary function measurements, including repeated arterial blood gases over three years. Airway obstruction, lung hyperinflation, markers of systemic inflammation and cardiovascular health, exacerbation frequency, smoking habits, and body composition were tested as possible predictors of PaO2 and first episode of hypoxemia. RESULTS: In multivariate adjusted longitudinal analyses, forced expiratory volume in 1 second, total lung capacity and functional residual capacity (all in% predicted), resting heart rate and fat mass index were all associated with overall PaO2 (all P < 0.005). We found no change in PaO2 over time (ρ = 0.33), nor did we find evidence that any of the tested variables predicted change in PaO2 over time. In multivariate adjusted survival analyses, functional residual capacity and resting heart rate were predictors of episodic hypoxemia (both ρ < 0.005). CONCLUSIONS: This longitudinal study identified pulmonary, cardiac and metabolic risk factors for overall PaO2 and episodic hypoxemia, but detected no change in PaO2 over time.

Genetic association between human chitinases and lung function in COPD.

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

Recommendations for epidemiological studies on COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

Candidate genes for COPD in two large data sets.

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.

Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies.

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.

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD.

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.

Body composition and plasma levels of inflammatory biomarkers in COPD.

Previous studies suggest a relationship between systemic inflammation and body composition in chronic obstructive pulmonary disease (COPD). We examined the relationships between body composition (fat free mass index (FFMI) kg·m(-2) and fat mass index (FMI) kg·m(-2)) and three plasma inflammatory markers C-reactive Protein (CRP), soluble tumour necrosis factor receptor 1 (sTNF-R1) and osteoprotegerin (OPG) in 409 stable COPD patients (aged 40-75 yrs, Global Initiative for Obstructive Chronic Lung Disease (GOLD) categories II-IV, 249 male) from the Bergen COPD Cohort Study in Norway. FFMI and FMI were measured by bioelectrical impedance. Plasma CRP (µg·mL(-1)), sTNF-R1 (pg·mL(-1)) and OPG (ng·mL(-1)) were determined by enzyme immunoassays. Correlations and Kruskal-Wallis tests were used for bivariate analyses. Linear regression models were fitted for each of the three markers, CRP, sTNF-R1 and OPG, with FFMI and FMI as explanatory variables including sex, age, smoking habits, GOLD category, hypoxaemia, Charlson Comorbidity Index and inhaled steroid use as potential confounders. CRP and sTNF-R1 levels correlated positively with both FFMI and FMI. The adjusted regression coefficients for an increase in logCRP per unit increase in FFMI was 1.23 (1.14-1.33) kg·m(-2) and 24.9 (11.8-38.1) kg·m(-2) for sTNF-R1. Higher FMI was associated with a lower OPG, with adjusted regression coefficient -0.14 (-0.23- -0.04), whereas FFMI was unrelated to OPG. In conclusion, COPD patients with low FFMI had lower not higher plasma levels of CRP and sTNF-R1, whereas higher fat mass was associated with higher CRP and sTNF-R1 and lower OPG.

Healthy hire effect, job selection and inhalation exposure among young adults with asthma.

The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures. The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status. Of the respondents, 8% (n = 1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68-0.92) or low (0.91; 0.80-1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma. Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures.

Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study.

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40-75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.

Transthoracic fine-needle aspiration in the aetiological diagnosis of community-acquired pneumonia.

To investigate the safety and practicability of conducting transthoracic fine-needle aspiration (TFNA) in a general hospital setting, we applied the TFNA procedure to 20 patients hospitalized with community-acquired pneumonia (CAP) within 36 h of admission. Also, a preliminary assessment was made of the potential value of adding TFNA to conventional methods of diagnostic microbiology. TFNA was easy to perform and caused little discomfort, and no serious adverse events were observed. In spite of ongoing antimicrobial treatment, a likely aetiological diagnosis was established for 14 of 20 (70%) of the patients. TFNA may provide important additional information on the aetiology of CAP.

Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking.

We investigated how quantitative high-resolution computed tomography (HRCT) measures of emphysema and airway wall thickness (AWT) vary with sex, age and smoking history. We included 463 chronic obstructive pulmonary disease (COPD) cases and 431 controls. All included subjects were current or ex-smokers aged > or = 40 yrs, and all underwent spirometry and HRCT examination. The HRCT images were quantitatively assessed, providing indices on lung density and airway dimensions. The median (25-75th percentile) %LAA950 (% low-attenuation area < -950 HU) was 8.9 (3-19) and 4.7 (1-16) in male and female COPD cases, respectively, and 0.71 (0.3-1.6) and 0.32 (0.1-0.8) in male and female controls, respectively. %LAA950 was higher in ex-smokers and increased with increasing age and with increasing number of pack-years. The mean+/-SD standardised AWT was 0.504+/-0.030 and 0.474+/-0.031 in male and female COPD cases, respectively, and 0.488+/-0.028 and 0.463+/-0.025 in male and female controls, respectively. AWT decreased with increasing age in cases, and increased with the degree of current smoking in all subjects. We found significant differences in quantitative HRCT measures of emphysema and AWT between varying sex, age and smoking groups of both control and COPD subjects.

Clinical data discriminating between adults with positive and negative results on bronchodilator testing.

OBJECTIVE: To evaluate how spirometry, symptoms and smoking discriminate between subjects who are responsive to bronchodilator testing and those who are non-responsive, and to examine how cut-off points of positive tests are related to symptoms of chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Subjects aged 47-48 and 71-73 years living in Bergen, Norway, were recruited. The 3506 participants (69%) filled in questionnaires and performed a bronchodilator test using salbutamol. RESULTS: Tests were positive (forced expiratory volume in 1 s [Delta FEV1] >or=200 ml and >or=12%) in 107 subjects (3%). In logistic regression, spirometry (FEV1 < 80%, OR 6.0, 95%CI 3.6-10.2, and FEV1/FVC < 0.70, OR 3.1, 95%CI 1.9-5.2) and pack-years >or= 20 (OR 0.3, 95%CI 0.2-0.7), but not symptoms, predicted the test outcome. FEV1% and FEV1/forced volume capacity (FVC) discriminated equally well between positive and negative tests (area under the receiver operating characteristic [ROC] curve 0.81, 95%CI 0.77-0.85 vs. 0.77, 95%CI 0.72-0.82). The largest likelihood ratio for positive tests was 5.4 (95%CI 3.8-7.8) using FEV1 < 80% and FEV1/FVC < 0.70. CONCLUSIONS: Spirometry and to a lesser extent smoking, but not symptoms, are useful in discriminating between middle-aged and elderly patients with positive and negative bronchodilator tests. Acute responses to salbutamol, expressed by commonly used Delta FEV1 cut-off points, are poorly related to COPD- and asthma-like symptoms.

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

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

Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1.

There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD. The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and beta2-adrenoreceptor. A total of 492 Caucasian smokers and former smokers were recruited from hospital databases and population cohort studies. In the present study, a protective effect of the EPHX1 Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta-analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a pooled OR of 0.5. The same effect has been found in several lung cancer studies. Effects for other candidate SNPs were weak or statistically insignificant, and probable genotyping error was common. In conclusion, the present data and meta-analysis support a role for microsomal epoxide hydroxylase in the aetiology of chronic obstructive pulmonary disease.

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

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

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

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

Indoor exposures and respiratory symptoms in a Norwegian community sample.

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 (CI) 1.0 to 2.4) for cough with phlegm to 2.3 (95% CI 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% CI 1.0 to 1.7) and 1.4 (95% CI 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.

Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study.

AIMS: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population-based, complete cohort of young preterms approaching adulthood. METHODS: Forty-six preterms with gestational age < or = 28 wk or birthweight < or = 1000 g, born between 1982 and 1985, were compared to the temporally nearest term-born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. RESULTS: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of preterms had a positive methacholine provocation test compared to 26% of controls. CONCLUSION: A substantially decreased FEV1, increased bronchial hyperresponsiveness and a number of established risk factors for steeper age-related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.

Pulmonary gas exchange and educational level: a community study.

Socio-economic status (SES) is related to increased risk of airway disease in terms of forced expiratory volume in one second (FEV1) and forced vital capacity. No data are available as to what extent SES predicts alveolar function in a general population. In this cross-sectional study, 1,275 subjects aged 18-73 yrs underwent pulmonary testing, including the single-breath carbon monoxide transfer capacity of the lungs (TL,CO). Educational level was used as an index for SES. Mean +/- SD TL,CO % predicted was 97% among those with primary school education, 99% among those with secondary school education and 104% among those with a university degree. In a multiple linear regression analysis, adjusting for age, height, haemoglobin, carboxyhaemoglobin, smoking habits, occupational exposure, FEV1 and body mass index, TL,CO was significantly related to educational level in males but not in females. Occupational exposure was not significant. In this study, socio-economic status was found to be an independent determinant of TL,CO. Even in an affluent country such as Norway, socio-environmental risk factors may differ based on individuals' SES. Such risk factors may, for instance, be higher exposure to airborne pollutants, poorer housing conditions, or lower consumption of fruit and vegetables. Further exploration is called for.