Long-term therapy in COPD: any evidence of adverse effect on bone?

Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis

Self-Reported Cardiovascular Disease and the Risk of Lung Cancer, the HUNT Study

Introduction:Inflammation is involved in development of lung cancer and cardiovascular disease (CVD), and we hypothesize that self-reported CVD is an independent risk factor for lung cancer.Methods:Data from the Nord-Trøndelag Health Study (1984–2008) linked to the Norwegian Cancer and Death Cause Registry were analyzed stratified by smoking status. In total, 97,087 persons (1,634,967 person years) were included (never smokers 567,575 person years, former smokers 295,685 person years, current smokers 444,922 person years, and unknown 326,785 person years) and followed for an average of 15 years. The proportional hazard model was applied to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for self-reported CVD on lung cancer incidence rate adjusted for age, sex, body mass index, burden of tobacco smoking and chronic cough with phlegm.Results:1080 cases of lung cancer (1.1%) occurred. A total of 5981 (6.9%) participants had at baseline or developed during follow-up self-reported CVD. After adjusting for confounders, self-reported CVD was an independent risk factor for the development of lung cancer in former (HR [95% CI] 1.74 [1.11–2.73]) and current smokers (HR [95% CI] 1.38 [1.04–1.83]), but not in never smokers (HR [95% CI] 0.87 [0.34–2.23]).Conclusions:Self-reported CVD was independently associated with increased occurrence of lung cancer in former and current smokers. CVD may be a novel risk factor for lung cancer screening

Prolonged Survival in Patients with Lung Cancer with Diabetes Mellitus

IntroductionPatients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer.MethodWe analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined.ResultsOne thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41–0.75) as compared with without.ConclusionPatients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus

A Validated Clinical Risk Prediction Model for Lung Cancer in Smokers of All Ages and Exposure Types:A HUNT Study

Lung cancer causes >1·6 million deaths annually, with early diagnosis being paramount to effective treatment. Here we present a validated risk assessment model for lung cancer screening.The prospective HUNT2 population study in Norway examined 65,237 people aged >20 years in 1995–97. After a median of 15·2 years, 583 lung cancer cases had been diagnosed; 552 (94·7%) ever-smokers and 31 (5·3%) never-smokers. We performed multivariable analyses of 36 candidate risk predictors, using multiple imputation of missing data and backwards feature selection with Cox regression. The resulting model was validated in an independent Norwegian prospective dataset of 45,341 ever-smokers, in which 675 lung cancers had been diagnosed after a median follow-up of 11·6 years.Our final HUNT Lung Cancer Model included age, pack-years, smoking intensity, years since smoking cessation, body mass index, daily cough, and hours of daily indoors exposure to smoke. External validation showed a 0·879 concordance index (95% CI [0·866–0·891]) with an area under the curve of 0·87 (95% CI [0·85–0·89]) within 6 years. Only 22% of ever-smokers would need screening to identify 81·85% of all lung cancers within 6 years.Our model of seven variables is simple, accurate, and useful for screening selection. Keywords: Early diagnosis, Lung cancer prediction, Ever-smokers, All smokers, All ages, Data-driven, Feature selection, External validatio

Association between pulmonary function and peak oxygen uptake in elderly: the Generation 100 study

Background Although reduced function of the respiratory system limits peak oxygen uptake in diseases affecting the lungs or airways, the healthy respiratory system is thought to have a spare capacity for oxygen transport and uptake, and is not considered a limiting factor for peak oxygen uptake in healthy people. However, lung function declines with age and could theoretically limit peak oxygen uptake in elderly. We examined the association between peak oxygen uptake and lung function indices in an elderly population with the hypothesis that lung function indices would be associated with VO 2peak up to a threshold value situated above the lower limits of normal lung function for our population. Methods Spirometry, gas diffusion tests and incremental work tests were performed in 1443 subjects (714 women) aged 69–77 years. Association between lung function indices and peak oxygen uptake was studied with hockey-stick regression. Results Forced expiratory volume in 1 s (FEV 1 ) had a positive association with peak oxygen uptake up to, but not above, a threshold value of 2.86 l for men, and 2.13 l for women (lower limit of normal 2.73 and 1.77 l respectively). A corresponding threshold was found for diffusing capacity of the lung for carbon monoxide (D LCO ) for men at 9.18 mmol/min/kPa (lower limit of normal 6.84 mmol/min/kPa). D LCO for women and D LCO divided by alveolar volume (D LCO /VA) for both sexes had a significant linear relationship to VO 2peak (p < 0.05), but no significant threshold value was found in these associations. Conclusions Threshold values for FEV 1 for both sexes and D LCO for men were identified. These lung function indices had a positive association with VO 2peak up to these threshold values, but not above. The identified threshold values were above lower limits of normal for FEV 1 and D LCO .publishedVersio

Adiposity and asthma in adults: a bidirectional Mendelian randomization analysis of the HUNT Study

This article has been accepted for publication in Thorax, 2019 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/thoraxjnl-2019-213678. © Authors (or their employer(s))Background - We aimed to investigate the potential causal associations of adiposity with asthma overall, asthma by atopic status or by levels of symptom control in a large adult population and stratified by sex. We also investigated the potential for reverse causation between asthma and risk of adiposity. Methods - We performed a bidirectional one-sample Mendelian randomisation (MR) study using the Norwegian Nord-Trøndelag Health Study population including 56 105 adults. 73 and 47 genetic variants were included as instrumental variables for body mass index (BMI) and waist-to-hip ratio (WHR), respectively. Asthma was defined as ever asthma, doctor-diagnosed asthma and doctor-diagnosed active asthma, and was further classified by atopic status or levels of symptom control. Causal OR was calculated with the Wald method. Results - The ORs per 1 SD (4.1 kg/m2) increase in genetically determined BMI were ranged from 1.36 to 1.49 for the three asthma definitions and similar for women and men. The corresponding ORs for non-atopic asthma (range 1.42–1.72) appeared stronger than those for the atopic asthma (range 1.18–1.26), but they were similar for controlled versus partly controlled doctor-diagnosed active asthma (1.43 vs 1.44). There was no clear association between genetically predicted WHR and asthma risk or between genetically predicted asthma and the adiposity markers. Conclusions - Our MR study provided evidence of a causal association of BMI with asthma in adults, particularly with non-atopic asthma. There was no clear evidence of a causal link between WHR and asthma or of reverse causation

Asthma, asthma control and risk of ischemic stroke:The HUNT study

Background: Asthma, a chronic inflammatory airway disease, shares common pathophysiological mechanisms with ischemic stroke. The aim of the study is to assess the association between asthma, levels of asthma control and ischemic stroke risk in men and women and by smoking habits. Methods: This prospective population-based cohort study utilized data on 58 712 adults from HUNT Study in Norway free from stroke. Self-reported asthma was categorized as ever asthma, non-active asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined ac-cording to the Global Initiative for Asthma questionnaire and was categorized into controlled and not controlled asthma. Stroke was ascertained by linking HUNT data with Nord-Trøndelag hospital records and the Norwegian Patient Registry. Results: During a mean follow-up of 17.3 �5.3 years, 2619 participants (4.5%) had a first stroke. Not controlled asthma was associated with a modest increased risk of stroke (adjusted HR 1.34, 95%CI 1.03–1.73). Subgroup analyses revealed that the respective association was stronger among those with history of smoking (HR 1.48, 95%CI 1.10–2.00) and males (HR 1.55, 95%CI 1.12–2.16) while absent in non-smokers (HR 1.02, 95%CI 0.61–1.70) and females (HR 1.05, 95%CI 0.69–1.60). Likewise, active asthma was associated with similar increased stroke risk among smokers and males and absent in non-smokers and females. Conclusions: Symptomatic and active asthma was associated with a modest increased relative risk for ischemic stroke in smokers and males. Future studies should clarify the difference in risks and mechanisms between different phenotypes of asthma