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Biomedical subjects

J Vestbo

Publications and source records attributed to J Vestbo.

At least 19 recordsLinked to original sources
PubMed2006

Potential misclassification of causes of death from COPD.

Little is known about causes of death in chronic obstructive pulmonary disease (COPD) and the validity of mortality statistics in COPD. The present authors examined causes of death using data from the Copenhagen City Heart Study. Of the 12,979 subjects with sufficient data from the baseline examination during 1976-1978, 6,709 died before 2001. Of these, 242 died with COPD as cause of death. Among subjects with at least severe COPD at baseline, only 24.9% had COPD as cause of death and, in almost half of the cases where COPD was listed as cause of death, the subject had a normal forced expiratory volume in one second /forced vital capacity ratio at baseline. In COPD patients, having COPD on the death certificate was associated with chronic mucus hypersecretion (CMH) at baseline, an odds ratio (OR) of 3.6 (95% confidence interval 1.7-7.7), and being female (OR 2.7 (1.3-5.6)). In subjects without COPD, CMH and smoking were predictors of COPD as underlying cause of death, ORs 2.3 (1.5-3.7) and 2.2 (1.4-3.6), respectively. It was concluded that chronic obstructive pulmonary disease is underreported on death certificates, that biases in the use of chronic obstructive pulmonary disease as cause of death can be assessed, and that possible "over-diagnosis" of chronic obstructive pulmonary disease on death certificates in subjects unlikely to have significant disease should initiate caution when using causes of mortality in chronic obstructive pulmonary disease epidemiology.

Cause of Death↗
PubMed2006

Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene.

BACKGROUND: Asthma is a complex genetic disorder. Many studies have suggested that chromosome 12q harbours a susceptibility gene for asthma and atopy. Linkage on chromosome 12q24.21-q24.33 was investigated in 167 Danish families with asthma. METHODS: A two step procedure was used: (1) a genome-wide scan in one set of families followed by (2) fine scale mapping in an independent set of families in candidate regions with a maximum likelihood score (MLS) of > or =1.5 in the genome-wide scan. Polymorphisms in a candidate gene in the region on 12q24.33 were tested for association with asthma in a family based transmission disequilibrium test. RESULTS: An MLS of 3.27 was obtained at 12q24.33. The significance of this result was tested by simulation, resulting in a significant empirical genome-wide p value of 0.018. To our Knowledge, this is the first significant evidence for linkage on chromosome 12q, and suggests a candidate region distal to most previously reported regions. Three single nucleotide polymorphisms in splicing factor, arginine/serine-rich 8 (SFRS8) had an association with asthma (p < or = 0.0020-0.050) in a sample of 136 asthmatic sib pairs. SFRS8 regulates the splicing of CD45, a protein which, through alternative splice variants, has an essential role in activating T cells. T cells are involved in the pathogenesis of atopic diseases such as asthma, so SFRS8 is a very interesting candidate gene in the region. CONCLUSIONS: Linkage and simulation studies show that the very distal part of chromosome 12q contains a gene that increases the susceptibility to asthma. SFRS8 could act as a weak predisposing gene for asthma in our sample.

Asthma↗
PubMed2006

Highly significant linkage to chromosome 3q13.31 for rhinitis and related allergic diseases.

BACKGROUND: Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus. OBJECTIVE: To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped in candidate regions showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans. RESULTS: Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed. CONCLUSION: This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.

Asthma↗
PubMed2006

Inhaled corticosteroids and decline of lung function in community residents with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) constitute the cornerstone of treatment for asthma. Many studies have reported beneficial short term effects of these drugs, but there are few data on the long term effects of ICS on the decline in forced expiratory volume in 1 second (FEV(1)). This study was undertaken to determine whether adults with asthma treated with ICS have a less pronounced decline in FEV(1) than those not treated with ICS. METHODS: Two hundred and thirty four asthmatic individuals from a longitudinal epidemiological study of the general population of Copenhagen, Denmark were divided into two groups; 44 were treated with ICS and 190 were not treated with ICS. The annual decline in FEV(1) was measured over a 10 year follow up period. RESULTS: The decline in FEV(1) in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year in the 190 patients not receiving this treatment (p<0.001). The linear regression model with ICS as the variable of interest and sex, smoking, and wheezing as covariates showed that treatment with ICS was associated with a less steep decline in FEV(1) of 18 ml/year (p = 0.01). Adjustment for additional variables including age, socioeconomic status, body mass index, mucus hypersecretion, and use of other asthma medications did not change these results. CONCLUSIONS: Treatment with ICS is associated with a significantly reduced decline in ventilatory function.

Administration, Inhalation↗
PubMed2006

Developing COPD: a 25 year follow up study of the general population.

BACKGROUND: Smokers are more prone to develop chronic obstructive pulmonary disease (COPD) than non-smokers, but this finding comes from studies spanning 10 years or less. The aim of this study was to determine the 25 year absolute risk of developing COPD in men and women from the general population. METHODS: As part of the Copenhagen City Heart Study, 8045 men and women aged 30-60 years with normal lung function at baseline were followed for 25 years. Lung function measurements were collected and mortality from COPD during the 25 year observation period was analysed. RESULTS: The percentage of men with normal lung function ranged from 96% of never smokers to 59% of continuous smokers; for women the proportions were 91% and 69%, respectively. The 25 year incidence of moderate and severe COPD was 20.7% and 3.6%, respectively, with no apparent difference between men and women. Smoking cessation, especially early in the follow up period, decreased the risk of developing COPD substantially compared with continuous smoking. During the follow up period there were 2912 deaths, 109 of which were from COPD. 92% of the COPD deaths occurred in subjects who were current smokers at the beginning of the follow up period. CONCLUSION: The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.

Adult↗
PubMed2006

The natural history of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the USA, and it remains one of the few diseases that continues to increase its numbers. The development and progression of COPD can vary dramatically between individuals. A low level of lung function remains the cornerstone of COPD diagnosis and is a key predictor of prognosis. Lung function, however, is not the only factor in determining morbidity and mortality related to COPD, with factors such as body mass index, exercise capability and comorbid disease being important predictors of poor outcomes. Exacerbations of COPD are additional important indicators of both quality of life and outcomes in COPD patients. Definitions of exacerbations can vary, ranging from an increase in symptoms to COPD-related hospitalisations and death. COPD exacerbations are more common in patients with lower levels of lung function and may lead to more rapid declines in lung function. Better understanding of the natural history of COPD may lead to better definitions of specific COPD phenotypes, better interventions and improved outcomes.

Cardiovascular Diseases↗
PubMed2005

Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease.

BACKGROUND: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown. METHODS: A pooled analysis, based on intention to treat, of individual patient data from seven randomised trials (involving 5085 patients) was performed in which the effects of inhaled corticosteroids and placebo were compared over at least 12 months in patients with stable COPD. The end point was all-cause mortality. RESULTS: Overall, 4% of the participants died during a mean follow up period of 26 months. Inhaled corticosteroids reduced all-cause mortality by about 25% relative to placebo. Stratification by individual trials and adjustments for age, sex, baseline post-bronchodilator percentage predicted forced expiratory volume in 1 second, smoking status, and body mass index did not materially change the results (adjusted hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.55 to 0.96). Although there was considerable overlap between subgroups in terms of effect sizes, the beneficial effect was especially noticeable in women (adjusted HR 0.46; 95% CI 0.24 to 0.91) and former smokers (adjusted HR 0.60; 95% CI 0.39 to 0.93). CONCLUSIONS: Inhaled corticosteroids reduce all-cause mortality in COPD. Further studies are required to determine whether the survival benefits persist beyond 2-3 years.

Administration, Inhalation↗
PubMed2005

Convergence of the epidemiology and pathology of COPD.

The epidemiology of chronic obstructive pulmonary disease (COPD) has been dominated by one hypothesis stating that cigarette smoking and chronic bronchitis were the key to pathogenesis and another that asthma, chronic bronchitis, and even emphysema are related to different expressions of a primary airway abnormality. The first hypothesis was rejected in the late 1960s based on a longitudinal study of working men where only a fraction of smokers developed COPD and where development of COPD was independent of the absence or presence of chronic bronchitis. Chronic bronchitis in more advanced COPD was subsequently associated with a more rapid decline in lung function and more frequent exacerbations. The second hypothesis is more difficult to test but longitudinal studies have shown that the presence of bronchial hyperresponsiveness may predict the subjects who go on to develop COPD. This brief review attempts to reconcile these findings with the pathology found in the lung.

Female↗
PubMed2005

Measuring bronchodilation in COPD clinical trials.

AIMS: The aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV1, FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials. METHODS: Twenty-four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 microg) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI). RESULTS: Significant effects (P < 0.05) were detected after 20 microg by X5 (18.5% CI 9.8-27.2) RF (11.1% CI 7.2-15.0) and sGaw (21.5% CI 10.1-32.9), and after 50 microg by R5 (16.7% CI 10.8-22.5) and Raw (19.7% CI 13.0-26.4). FEV1 was less sensitive, detecting significant bronchodilation at 100 microg (10.2% CI 7.4-12.9). CONCLUSIONS: We conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials.

Albuterol↗
PubMed2005

Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease.

BACKGROUND: Combined treatment with inhaled corticosteroids and long acting beta2 agonists is approved for the treatment of chronic obstructive pulmonary disease (COPD), but little is known about the onset of effect of the combination. METHODS: Data were used from 1465 patients with COPD entered into a large 1 year double blind trial with daily measurements of peak expiratory flow (PEF) and symptom scores. RESULTS: PEF was significantly higher after 1 day in patients treated with salmeterol 50 microg twice daily or the salmeterol/fluticasone propionate combination 50/500 microg twice daily than placebo. In patients treated with fluticasone propionate 500 microg twice daily alone, PEF differed from placebo after 2 days. The differences after 2 weeks compared with placebo were 16 l/min (95% confidence interval (CI) 11 to 21), 11 l/min (95% CI 6 to 16), and 27 l/min (95% CI 22 to 33) for salmeterol, fluticasone propionate, and the salmeterol/fluticasone propionate combination, respectively. For all treatments the effect on PEF after 2 weeks was comparable to that seen at the end of the study. The difference between the salmeterol/fluticasone propionate combination and placebo after 2 weeks as a percentage of baseline was similar for PEF and clinic forced expiratory volume in 1 second (FEV1). Differences in breathlessness scores were statistically significant after 1 day for the group treated with salmeterol alone and after 2 days for the combination group. The 2 week change in FEV1 was only partly indicative of a long term response in individual patients. CONCLUSIONS: The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks.

Administration, Inhalation↗
PubMed2005

Effect of treatments on the progression of COPD: report of a workshop held in Leuven, 11-12 March 2004.

During the last decade several long term studies of interventions in patients with COPD have been published. This review analyses the potential of these interventions to alter the progression of the condition. The only treatment that has unequivocally been shown to reduce the rate of decline in FEV(1) is smoking cessation. Active psychological intervention in combination with pharmacotherapy is required. Other treatments may have an effect on the rate of decline in FEV(1) but this appears to be very small, at most. Several treatments affect the exacerbation rate and therefore might affect the progression of the disease. Further studies are warranted to examine this effect.

Administration, Inhalation↗
PubMed2005

Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease.

Increasingly, exhaled breath condensate (EBC) is being used to sample airway fluid from the lower respiratory tract. EBC pH may be a biomarker of airway inflammation in chronic obstructive pulmonary disease (COPD). In this study, the reproducibility of EBC pH in COPD was investigated. A total of 36 COPD patients and 12 healthy nonsmoking subjects participated in several investigations: duration of argon deaeration, within-sample variability, effect of freezing, leaving samples at room temperature, nose-peg use, within- (WD) and between-day (BD) variability. Analysis of repeated measurements was performed using the Bland-Altman method with limits of agreement (LOA; mean difference+/-2 SD). Wider LOA indicate greater variability. EBC pH became significantly higher with argon deaeration for < or =5 min. Variability during sample analysis was minimal; LOA of within-sample variability, freezing for 3 months and leaving at room temperature for 3 h were -0.29-0.45, -0.37-0.42 and -0.13-0.09, respectively. In contrast, variability due to nose-peg use (LOA -1.46-1.99), WD (LOA -1.50-2.48) and BD variability (LOA -2.52-3.02) were higher in COPD. In healthy nonsmoking subjects, nose-peg use (LOA -0.27-0.23), WD (LOA -0.33-0.40) and BD variability (LOA -0.46-0.44) were more reproducible. In conclusion, the variability of exhaled breath condensate pH in chronic obstructive pulmonary disease patients is mainly due to changes in airway pH over time, which are not seen in healthy nonsmoking subjects. Reasons for these fluctuations in exhaled breath condensate pH are unclear and require further investigation.

Adult↗
PubMed2004

The TORCH (towards a revolution in COPD health) survival study protocol.

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.

Administration, Inhalation↗
PubMed2004

Chronic bronchitis: should it worry us?

BACKGROUND: Chronic bronchitis (CB) has been studied using standardized questionnaires for decades. From being the key element in the 'British hypothesis' chronic bronchitis was reduced to being an innocent disorder in the 1980s. However, there is now good evidence that chronic bronchitis is associated with an increased risk from both overall and chronic obstructive pulmonary disease (COPD) specific mortality. Presumably through increasing the frequency of lower respiratory tract infections chronic bronchitis is associated with excess decline in lung function, hospital admission and other disease specific outcomes. The prevalence of chronic bronchitis increases with increasing age and the burden associated with chronic bronchitis in this growing proportion of the population is large. Vital prognosis in the elderly is affected by CB and this condition presumably deserves more attention from the medical profession.

Bronchitis, Chronic↗