Anders Løkke

Early detection of COPD in general practice

Background and aim Early detection enables the possibility for interventions to reduce the future burden of COPD. The Danish National Board of Health recommends that individuals >35 years with tobacco/occupational exposure, and at least 1 respiratory symptom should be offered a spirometry to facilitate early detection of COPD. The aim, therefore, was to provide evidence for the feasibility and impact of doing spirometry in this target population. Methods Participating general practitioners (GPs) (n = 335; 10% of the Danish GPs) recruited consecutively, subjects with >35 years exposure, no previous diagnosis of obstructive lung disease, and at least 1 of the following symptoms: cough, dyspnea, wheezing, sputum, or recurrent respiratory infection. Data on age, smoking status, pack-years, body mass index (BMI), dyspnea score (Medical Research Council, MRC), and pre-bronchodilator spirometry (FEV1, FEV1% predicted, FEV1/FVC) were obtained. Results A total of 3.095 (51% females) subjects was included: mean age 58 years, BMI 26.3, and 31.5 pack-years. The majority of subjects (88%) reported MRC score 1 or 2. FEV1/FVC-ratio ≤ 0.7 was found in 34.8% of the subjects; the prevalence of airway obstruction increased with age and decreased with increasing BMI, and was higher in men and current smokers. According to the level of FEV1, 79% of the subjects with airway obstruction had mild to moderate COPD. Conclusions More than one-third of the recruited subjects had airway obstruction (FEV1/ FVC < 0.7). Early detection of COPD appears to be feasible through offering spirometry to adults with tobacco/occupational exposure and at least 1 respiratory symptom.

Detection of previously undiagnosed cases of COPD in a high-risk population identified in general practice.

Abstract Background and Aim: Under-diagnosis of COPD is a widespread problem. This study aimed to identify previously undiagnosed cases of COPD in a high-risk population identified through general practice. Methods: Participating GPs (n = 241) recruited subjects with no previous diagnosis of lung disease, >35 yrs, and at least one respiratory symptom. Age, smoking status, pack-years, BMI, dyspnoea score (MRC), and pre-bronchodilator spirometry data was obtained. Subjects with airway obstruction (FEV1/FVC ≤ 0.7) at initial spirometry were tested for reversibility, according to Danish COPD guidelines, with bronchodilator and, if necessary, corticosteroids in order to confirm a diagnosis of COPD. Results: A total of 4.049 (49% females) subjects were included; mean age 58 yrs, BMI 27, and 32 pack-years. The COPD prevalence was 21.7%; 8.3% in subjects younger than 48 years. Most patients were classified in GOLD stages I and II (36% and 50%, respectively). The number needed to screen (NNS) for a new diagnosis of COPD was 4.6. COPD diagnosis was related to gender, age, BMI (p < 0.001), pack-years, and cough (p < 0.001), wheezing (p < 0.001) and sputum production (p = 0.002). A threshold of 10% pre-test risk of COPD would have reduced the number of spirometry tests by 35% although 90% of the patients with COPD would still have been identified (NNS 3.9). Conclusions: Of the at-risk subjects studied, 22% were diagnosed with COPD. A case-finding strategy providing questionnaire assessment and diagnostic spirometry to high-risk subjects in primary care, and therefore, identifies a large proportion of undiagnosed COPD patients, especially in the early stages of the disease.

Direct and indirect economic and health consequences of COPD in Denmark: a national register-based study: 1998–2010

Objective Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide, but longitudinal studies of the economic consequences of COPD are scarce. This Danish study evaluated for the first time ever the economic consequences of COPD of an entire nation before and after the diagnosis. Setting Records from the Danish National Patient Registry (1998–2010), direct and indirect costs, including frequency of primary and secondary sector contacts and procedures, medication, unemployment benefits and social transfer payments were extracted from national databases. Participants 131 811 patients with COPD were identified and compared with 131 811 randomly selected controls matched for age, gender, educational level, residence and marital status. Primary and secondary outcome measures Direct and indirect economic and health consequences of COPD in Denmark in the time period 1998–2010. Results Patients with COPD had a poor survival. The average (95% CI) 12-year survival rate was 0.364 (0.364 to 0.368) compared with 0.686 among controls (0.682 to 0.690). COPD was associated with significantly higher rates of health-related contacts, medication use and higher socioeconomic costs. The employment and the income rates of employed patients with COPD were significantly lower compared with controls. The annual net costs, including social transfers were €8572 for patients with COPD. These consequences were present up to 11 years before first-time diagnosis in the secondary healthcare sector and became more pronounced with disease advancement. Conclusions This study provides unique national data on direct and indirect costs before and after initial diagnosis with COPD in Denmark as well as mortality, health and economic consequences for the individual and for society. It could be speculated that early identification and intervention might contribute to the solution.

Severe interstitial lung disease following treatment with certolizumab pegol: a case report

To the Editor: Over the past decade, the understanding of autoimmune diseases and the development of biological agents have radically changed the treatment paradigm for severe rheumatoid arthritis. Several tumour necrosis factor (TNF)-α inhibitors are available for clinical use, relieving symptoms and reducing the likelihood of relapse in patients not responding successfully to disease-modifying antirheumatic drugs; however, there are limited data regarding the safety of, in particular the newest, TNF-α inhibitor. Drug-associated interstitial lung disease is a well-known serious and potentially fatal adverse effect of early TNF-α inhibitor use. Being a pegylated humanised Fab monoclonal antibody, certolizumab pegol (CZP) is different from other TNF-α inhibitors. In clinical trials it has been shown to be just as, or even more, efficacious in the treatment of rheumatoid arthritis in combination with methotrexate compared with some of the earlier TNF-α inhibitors [1]. According to the US Food and Drug Administration and the European Medicines Agency, there have been no severe non-infectious adverse lung effects of CZP use. However, a systematic review of the literature revealed two previous cases of CZP-associated interstitial lung disease, one with fatal outcomes [2, 3]. This is a report of a patient with rheumatoid arthritis who developed severe acute pneumonitis after treatment with CZP. The patient is a 72-year-old female who had suffered from severe erosive seropositive (rheumatoid factor and …

A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality

Objectives To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD. Design Matched cohort study. Setting The study was conducted in Denmark, using nationwide, prospectively collected data. Participants Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD. Main outcome measures Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models. Results The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index. Conclusions ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.

Detection of COPD in a high-risk population: should the diagnostic work-up include bronchodilator reversibility testing?

Background Underdiagnosis of chronic obstructive pulmonary disease (COPD) is widespread. Early detection of COPD may improve the outcome by timely smoking cessation, a change in lifestyle, and treatment with an inhaled bronchodilator (BD). The objective of this study was to evaluate the diagnostic role of BD reversibility testing in early COPD case finding. Methods General practitioners (n=241) consecutively recruited subjects aged ≥35 years with relevant exposure (history of smoking, and/or occupational exposure) and at least one respiratory symptom. Information on age, smoking status, body mass index, dyspnea score (Medical Research Council scale), and spirometry was obtained. Individuals with airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <0.70) underwent a BD test with an inhaled β2 agonist, which was considered positive if ΔFEV1 was >0.20 L and >12%. Asthma and COPD were, respectively, defined as an FEV1 increase >0.50 L and a post-BD FEV1/FVC <0.70. Results In total, 4,049 subjects (51% male) were included (mean age 58 years, body mass index 27, 32 pack-years of smoking). A significant BD response was found in 143 (15%) of the 937 subjects (23%) with airway obstruction at screening spirometry. In 59% of these subjects, the post-BD FEV1/FVC remained <0.70. In 24% of the subjects with pre-BD airway obstruction, the post-BD FEV1/FVC ratio was within the reference range. In subjects with confirmed COPD, the mean increase in FEV1 following BD was 0.11 L±0.10 L. The subjects with COPD and a significant BD response were characterized by a higher prevalence of dyspnea (72% versus 57%, P=0.02) but less cough (55% versus 75%, P=0.001) when compared with COPD subjects without BD reversibility. Conclusion Administration of a BD in COPD case finding is important in order to determine the post-BD FEV1/FVC ratio. Exclusion of subjects with a significant BD response may result in underdiagnosis of COPD, and we question the need for the BD reversibility test in the diagnostic screening algorithm in early COPD case finding.

The economic burden of Tuberculosis in Denmark 1998-2010. Cost analysis in patients and their spouses

OBJECTIVE To evaluate the economic burden of tuberculosis (TB) in Denmark, METHODS 8,433 Danish TB-patients (1998-2010) were matched with 33,707 controls by age, gender, civil status and geography. Health-related costs (health system contacts and -procedures, medications) and socio-economic parameters (foregone earnings and social transfer expenses) were calculated on data from national databases. The same information was obtained for 3,485 spouses of TB-patients, and 17,403 controls. RESULTS Health-related costs were higher for cases throughout the period. Before diagnosis, cases posed € 1,180 more health costs per year than controls. Excess health costs in the 2 years around diagnosing and treating TB were € 10,509. Cases received an average excess public transfer income of € 3,345 before vs. € 3,121 after diagnosis. Average employment income deficiency was € 11,635 before vs. € 13,885 after diagnosis, but the increasing difference showed a linear shape throughout the period. Spouses also had lower income, more social transfer, and posed higher health-related costs than matched controls. CONCLUSION We estimate the direct costs per TB patient to be €10,509. TB patients and their households are characterized by increasingly lower employment income, lower employment rate, and higher dependency on public transfer, but the socio/economic deterioration is rather a risk factor for TB than a direct consequence of the disease.

Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

Background Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes. Methods We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012. Results We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%). Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24). Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13). In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations. Conclusions Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality. Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations.

Mindfulness-based cognitive therapy in COPD: a cluster randomised controlled trial

A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) entering pulmonary rehabilitation (PR) report psychological distress, which is often accompanied by poor physical health status. Mindfulness-based cognitive therapy (MBCT) has been shown to improve psychological and physical outcomes in other chronic diseases. We therefore evaluated the efficacy of MBCT as an add-on to a standard PR programme in COPD. COPD patients eligible for PR were cluster randomised to receive either an 8-week, group-based MBCT programme as an add-on to an 8-week PR programme (n=39), or PR alone (n=45). The primary outcomes of psychological distress and physical health status impairment were measured with the Hospital Anxiety and Depression Scale (HADS) and the COPD Assessment Test (CAT) before randomisation (T1), mid- (T2) and post-intervention (T3), and at 3 (T4) and 6 (T5) months’ follow-up . A statistically significant time×arm effect was found for the HADS (Cohens d=0.62, 95% CIs (d)=0.18–1.06, p=0.010). The treatment effect on the CAT failed to reach statistical significance (d=0.42, 95% CIs (d)=−0.06–0.90, p=0.061). MBCT showed a statistically significant and durable effect on psychological distress, indicating that MBCT may be an efficacious add-on to standard PR programmes in COPD. Mindfulness-based cognitive therapy: an efficacious add-on to PR programmes to reduce psychological distress in COPD http://ow.ly/9noC30hnlxr

Economic and Health Consequences of COPD Patients and Their Spouses in Denmark—1998–2010

Abstract Objective: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of morbidity and mortality worldwide, but longitudinal studies of the economic consequences of COPD are scarce. This study evaluated the economic consequences of COPD patients in Denmark and their spouses at a national level before and after initial diagnosis. Methods: Using records from the Danish National Patient Registry (1998–2010), 171,557 patients with COPD and 86,260 spouses were identified; patients were compared with 664,821, and the spouses with 346,524, all controls were randomly selected and matched for age, gender and residence. Direct and indirect costs, including frequency of primary and secondary sector contacts and procedures, medication, unemployment benefits and social transfer payments were extracted from national databases for patients, spouses and controls. Results: COPD patients are earning approximately half of that of controls before diagnosis. After diagnosis this effect diminishes due to people getting older and retiring from work (65 years). Total health expenses are more than twice as high in the COPD group regardless of age and gender compared to controls. Spouses of COPD patients had significantly higher rates of health-related contacts, medication use and higher socioeconomic costs compared to controls. The employment and income rates of employed spouses of COPD patients were significantly lower compared to controls. Conclusion: This study provides unique data on the economic consequences of COPD patients in Denmark and their spouses as well as displaying the serious health consequences for the individual spouse and society. Second, data shows substantial impact of COPD on income level and health expenses regardless of age and gender. It could be speculated that early identification and intervention might contribute to more health and economic equality between patients and controls