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.

Baylisascaris procyonis infection in white-footed mice: predicting patterns of infection from landscape habitat attributes.

There is a growing body of evidence that habitat fragmentation resulting from anthropogenic land use can alter the transmission dynamics of infectious disease. Baylisascaris procyonis , a parasitic roundworm with the ability to cause fatal central nervous system disease in many mammals, including humans, is a zoonotic threat, and research suggests that parasite recruitment rates by intermediate hosts are highly variable among forest patches in fragmented landscapes. During 2008, we sampled 353 white-footed mice ( Peromyscus leucopus ) from 22 forest patches distributed throughout a fragmented agricultural ecosystem to determine the influence of landscape-level habitat attributes on infection rates of B. procyonis in mice. We characterized each mouse in terms of infection status and intensity of infection, and calculated (on a patch-wide basis) prevalence, mean abundance of B. procyonis , and mean intensity of infection. We used an information-theoretic approach to develop a suite of candidate models characterizing the influence of landscape attributes on each of our measured characteristics of B. procyonis infection in white-footed mice, based on previous knowledge of raccoon ( Procyon lotor ) ecology and B. procyonis distribution in agricultural ecosystems. We observed evidence of B. procyonis infection in mice across all 22 habitat patches sampled. However, parasite recruitment rates and intensity were highly variable among patches, and the results of our analyses suggest that spatial variability in B. procyonis infections was primarily driven by emergent properties of fragmented ecosystems. In particular, prevalence, abundance, and intensity of B. procyonis infections in mice were negatively associated with the size and connectivity of forest patches. These results support previous studies indicating that habitat fragmentation can alter the transmission dynamics of infectious disease, and suggest that factors below the scale of landscape, i.e., fine-scale habitat structure or demographic and behavioral attributes of intermediate and/or definitive hosts, also may be important for predicting patterns of B. procyonis infection in intermediate hosts.

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.

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.

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

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

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.

Decline in respiratory symptoms in service workers five months after a public smoking ban.

OBJECTIVE: To evaluate the effect of a total ban on smoking indoors in restaurants and other hospitality business premises in Norway, on respiratory symptoms among workers in the industry. METHODS: Phone interviews with 1525 employees in the hospitality business were conducted immediately before the enacting of the law. In a follow-up study five months later, 906 of the workers from the baseline sample participated. Questions were asked on demographic variables, passive smoking exposure, personal smoking, attitudes towards the law, and five respiratory symptoms. Change in symptom prevalence was analysed with McNemar's test and with analysis of variance (ANOVA) for repeated measures. RESULTS: The prevalence of all five symptoms declined after the ban; for morning cough from 20.6% to 16.2% (p < 0.01); for daytime cough from 23.2% to 20.9%; for phlegm cough from 15.3% to 11.8% (p < 0.05); for dyspnoea from 19.2% to 13.0% (p < 0.01); and for wheezing from 9.0% to 7.8%. ANOVA showed that the largest decline in symptom prevalence was seen among workers who themselves gave up smoking, and subjects with a positive attitude towards the law before it took effect. CONCLUSION: A significant decrease in respiratory symptoms among service industry workers was found five months after the enacting of a public smoking ban.

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.

The incidence of adult asthma: a review.

In recent years, several new studies have estimated the incidence of adult asthma. These studies vary in design and quality. The current paper summarises the findings of major population studies in the adult incidence of asthma. The pooled estimate of the adult incidence of asthma was 4.6 per 1000 person-years in women and 3.6 per 1000 person-years in men. The estimate among only general population cohort studies was higher, respectively 5.9 and 4.4 per 1000 person-years in women and men. The adult incidence of asthma was slightly higher in women than men. In the few studies that allowed the incidence of asthma to be estimated among those aged >50 years, there was a trend towards a higher incidence with age. It is thought likely that this is at least partly explained by misclassification with COPD. However, the current findings from these studies may imply that the incidence of asthma in the elderly has previously been under-estimated. Finally, the review shows that estimates of adult asthma incidence have tended to be higher in later studies, implying a rise in asthma incidence in adults within the timeframe of observation.

Remission of respiratory symptoms by smoking and occupational exposure in a cohort study.

Few studies have estimated the remission rates of respiratory symptoms in general populations. No community cohort studies have examined the impact of smoking cessation and previous dust or fumes exposure on the remission of respiratory symptoms. In the Hordaland County Study, an 11-yr community cohort (1985-1996/1997) from Western Norway, data from 2,819 subjects were used to examine the remission of six respiratory symptoms. The measured cumulative remission varied from 42.3% for morning cough to 58.4% for chronic cough. Smoking cessation was a significant predictor of remission of the cough symptoms and wheezing, with odds ratios (OR) (95% confidence intervals (CI)) varying from 2.2 (1.3-3.7) for wheezing to 6.2 (3.5-11.2) for morning cough, after adjustment for sex, age, pack-years smoked, previous dust or fumes exposure, and educational level. In those not previously exposed to dust or fumes, the adjusted OR (95% CI) for the remission of morning cough, phlegm cough, dyspnoea grade 2, attacks of dyspnoea and wheezing varied from 1.5 (0.9-2.5) for attacks of dyspnoea to 2.1 (1.1-3.9) for dyspnoea grade 2, as compared to those previously exposed to dust or fumes. This study suggests a beneficial effect of smoking cessation and an adverse effect of occupational exposure on the remission of respiratory symptoms.

Bias in retrospective studies of trends in asthma incidence.

There is evidence for an increase in adult asthma prevalence. Several retrospective studies have shown an increase in asthma incidence by year of birth, consistent with an increasing trend in asthma incidence. The validity of this retrospective approach is unknown. Retrospective and prospective asthma incidence by year of birth were compared in the same community, during the same time period, from two independent studies; a cohort study and a cross-sectional study in Western Norway. In the prospective study, subjects without asthma were followed from 1985-1996/1997. In the retrospective study in 1998, subjects reported the age at which the disease started. Analyses of incident asthma in the period 1985-1996 were compared between the studies. The retrospective analysis showed a large increase in asthma incidence by year of birth, with an odds ratio (OR) of 2.9 comparing those born in 1969 with those born in 1927. The prospective study showed the opposite, with an OR of 0.2 comparing those born in 1969 with those born in 1927. There was only a 20% difference in the cumulative incidence of asthma. To conclude, retrospective estimates of trends in asthma incidence are likely to be severely biased by differential recall.

A degeneracy study in the circulant and bordered-circulant approach to birdcage and planar coils.

A method for finding closed-form solutions for the normal mode frequencies of systems with circulant 2pi/2 symmetry was investigated. This method is particularly good for questions of degeneracy that arise when one considers parallel imaging techniques like SENSE and SMASH in MRI. It is applicable to systems that include birdcage coils as well as planar coils with the appropriate rotational symmetry. A proof is given that complete degeneracy of all normal mode frequencies is impossible when all mutual inductive couplings are included. We tested the method against measurements made on a planar coil array and on an 8-element birdcage coil. The inclusion of the co-rotating end-ring mode changes the fundamental symmetry of the system from circulant to "bordered circulant". Closed-form solutions for the normal mode frequencies of a bordered circulant system are also given.

A degeneracy study in the circulant and bordered-circulant approach to birdcage and planar coils.

A method for finding closed-form solutions for the normal mode frequencies of systems with circulant (2 pi/n) symmetry was investigated. This method is particularly useful for questions of degeneracy that arise when one considers parallel imaging techniques like SENSE and SMASH in MRI. It is applicable to systems that include birdcage coils as well as planar coils with the appropriate rotational symmetry. A proof is given that complete degeneracy of all normal mode frequencies is impossible when all mutual inductive couplings are included. We tested the method against measurements made on a planar coil array and on an 8-element birdcage coil. The inclusion of the co-rotating end-ring mode changes the fundamental symmetry of the system from circulant to 'bordered circulant.' Closed-form solutions for the normal mode frequencies of a bordered circulant system are also given.

Incidence of asthma and respiratory symptoms by sex, age and smoking in a community study.

The purpose of this study was to establish incidence rates for a wide range of respiratory symptoms and asthma, and relate them to sex, age, and smoking habits. A cohort established in 1985 as a random sample from the population of Western Norway, aged 15-70 yrs, was followed-up in 1996-1997. Of the initial cohort of 3,786 subjects, a total of 2,819 replied to mailed questionnaires at both baseline and follow-up. The 11-yrs cumulative incidence of asthma was 4.0% in males and 3.5% in females. For respiratory symptoms, the cumulative incidences for both sexes varied between 2.0% (dyspnoea grade 4) and 25.8% (wheezing), being higher in females than males for most symptoms. For calculation of odds ratios (ORs) multivariate logistic regression analyses were used. The sex and smoking-adjusted incidences increased by age for all symptoms except wheezing and attacks of dyspnoea. Those starting to smoke within the follow-up had ORs of 1.9-2.2 for the cough symptoms compared to never-smokers, after adjusting for sex, age, and pack-yrs. To conclude, the 11-yrs incidence of dyspnoea increased with increasing pack-yrs, after adjusting for sex, age, and changes in smoking habits. This indicated that when analysing other risk factors, adjustment has to be made for the risks posed by smoking, sex and age.

Toward shielding improvements in MRI gradients and other systems.

A new method is described for reducing the shielding-error function in the 'supershielding' approach to designing MRI systems. The method is thus shown to lead to significantly better shielding and better control of eddy current effects associated with gradient coils. To illustrate this technique, a set of results for a z-gradient coil is presented. A generalization to non-standard geometries can be made in a straightforward manner with the new method. The usefulness of the relationship of all fringe-field quantities to the shielding-error function is emphasized. The formal limit of perfect shielding in a 'least-squares' sense is shown for a simple strip-shield model along with a numerical eigenvalue study for comparison with the theoretical limit.

Application of the SUSHI method to the design of gradient coils.

An approach to potential improvements in magnetic field shielding for a gradient coil system with cylindrical geometry is presented, utilizing "supershielding" conditions for the currents on both the primary and the secondary coils. It is demonstrated that the field can be strongly suppressed everywhere outside a cylindrical shield coil radius, even though the finite-length active shield only partially surrounds a primary coil. The supershielding method, which is aimed at controlling eddy currents, still has sufficient freedom to maintain the desired magnetic field behavior inside the imaging volume. The trade-off is an additional primary current oscillation and increased current peaks and field energy. This method has been applied to design short transverse and axial gradient coils, giving substantially improved shielding compared to an apodization method. Magn Reson Med 45:147-155, 2001.

[Hospital admissions due to obstructive lung diseases and pneumonia in two hospital districts]. / Innleggelser for obstruktiv lungesykdom og pneumoni i to sykehusområder.

Admission rates for specific diseases in a defined district can be used as a coarse estimate of the need for health services. Such registration has not previously been conducted in the hospital districts of Bergen and Haugesund. We recorded all patients 16 years and older admitted to three hospitals for obstructive lung disease or pneumonia in the two hospital districts of Bergen and Haugesund in April to June 1997. A total of 438 patients were included in both districts, 246 with obstructive lung disease and 192 with pneumonia. The admission rate for obstructive lung disease was 359 per 100,000 inhabitants per year, for pneumonia 280 per 100,000 inhabitants per year. Median age was between 71 and 75 years for men and women for both diseases. 13% of patients with obstructive lung disease were readmitted to the hospital within 30 days. Obstructive lung disease and pneumonia are common causes of hospital admission, especially among older persons. The admission rates for both diseases combined were 639 per 100,000 adults per year in the hospital districts of Bergen and Haugesund.

Sertraline in social phobia.

Eleven consecutive SCID-diagnosed generalized social phobias without major depression, other prominent anxiety disorders, substance abuse, alcoholism or organic mental disorder, were treated, open label, with sertraline up to 200 mg daily for 12 weeks. There were seven completers. Of these, five showed substantial improvement, after being on sertraline 100 mg daily for two weeks (following no response to sertraline 50 mg daily for four weeks). There were few side effects among the completers. The four dropouts complained of side effects and loss of interest in continuing treatment. Final average dose for completers who responded was 170 mg daily.