Improving lung health in low-income and middle-income countries: from challenges to solutions

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage

Comorbid influences on generic health-related quality of life in COPD: A systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and of loss of disability-adjusted life years worldwide. It often is accompanied by the presence of comorbidity. OBJECTIVES: To systematically review the influence of COPD comorbidity on generic health-related quality of life (HRQoL). METHODS: A systematic review approach was used to search the databases Pubmed, Embase and Cochrane Library for studies evaluating the influence of comorbidity on HRQoL in COPD. Identified studies were analyzed according to study characteristics, generic HRQoL measurement instrument, COPD severity and comorbid HRQoL impact. Studies using only non-generic instruments were excluded. RESULTS: 25 studies met the selection criteria. Seven studies utilized the EQ-5D, six studies each used the SF-36 or SF-12. The remaining studies used one of six other instruments each. Utilities were calculated by four EQ-5D studies and one 15D study. Patient populations covered both early and advanced stages of COPD and ranged from populations with mostly stage 1 and 2 to studies with patients classified mainly stage 3 and 4. Evidence was mainly created for cardiovascular disease, depression and anxiety as well as diabetes but also for quantitative comorbid associations. Strong evidence is pointing towards the significant negative association of depression and anxiety on reduced HRQoL in COPD patients. While all studies found the occurrence of specific comorbidities to decrease HRQoL in COPD patients, the orders of magnitude diverged. Due to different patient populations, different measurement tools and different concomitant diseases the study heterogeneity was high. CONCLUSIONS: Facilitating multimorbid intervention guidance, instead of applying a parsimony based single disease paradigm, should constitute an important goal for improving HRQoL of COPD patients in research and in clinical practice

Excess costs of comorbidities in chronic obstructive pulmonary disease: A systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Comorbidities are often reported in patients with COPD and may influence the cost of care. Yet, the extent by which comorbidities affect costs remains to be determined. OBJECTIVES: To review, quantify and evaluate excess costs of comorbidities in COPD. METHODS: Using a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD. Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators. Mark-up factors were calculated for respective excess costs. Furthermore, a checklist of quality criteria was applied. RESULTS: Twelve studies were included. Nine evaluated comorbidity specific costs; three examined index-based results. Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs. The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases. On average the factors constituted a doubling of respective costs in the comorbid case. The main cost driver, among all studies, was inpatient cost. Indirect costs were not accounted for by the majority of studies. Study heterogeneity was high. CONCLUSIONS: The reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD. The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable

Influence of body mass on predicted values of static hyperinflation in COPD.

Introduction: For interpretation of body plethysmographic static hyperinflation, reference values are of crucial importance. Earliest reference values have been published by the European Coal and Steel Community (ECSC) and are based on sex, body height and age as predictors. As obesity can lead to a reduction of functional residual capacity (FRC) in lung-healthy subjects, more recent approaches included body weight or body surface area. This raises the question whether these models are appropriate in patients with COPD-induced hyperinflation. Method: Several FRC prediction models and their relation to body weight were analyzed in 1513 patients with stable COPD (mean [SD] age: 64.5 [8.2] years; GOLD grades 1–4: 219/722/484/88), a subset of the multicenter COPD and Systemic Consequences – Comorbidities Network cohort. Results: Absolute values of FRC were inversely related to body mass index (p<0.001). Applying the ECSC equations to calculate predicted values, this pattern was maintained (p<0.001). By contrast, an inverted, ie, positive, relation occurred when using equations that include body weight or surface area (p<0.001). The present analysis confirmed the inverse relation of body mass and FRC in COPD, resulting from a restrictive ventilatory pattern by diaphragm elevation and decreased chest wall compliance in obesity. The weight influence in the prediction models, as obtained from lung-healthy controls, appears to lead to an overcorrection and consequently to an inappropriate overestimation of hyperinflation as indicated by FRC %predicted in COPD. Conclusion: It is concluded that models not including body weight as predictor, like the classical ECSC equations, could be superior in the interpretation of FRC in COPD

Impact of lung function and exacerbations on health-related quality of life in copd patients within one year: Real-world analysis based on claims data.

Purpose: Real-world evidence on the impact of forced expiratory volume in one second (FEV1) and exacerbations on health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) is sparse especially with regard to GOLD ABCD groups. This study investigates how changes in FEV1 and exacerbations affect generic and disease-specific HRQoL in COPD patients over one year. Methods: Using German claims data and survey data, we classified 3016 COPD patients and analyzed their health status by GOLD groups AB and CD. HRQoL was measured with the disease-specific COPD assessment test (CAT) and the visual analog scale (VAS) from the generic Euro-Qol 5D-5L. We applied change score models to assess associations between changes in FEV1 (≥100 mL decrease/no change/≥100 mL increase) or the development of severe exacerbations with change in HRQoL. Results: FEV1 decrease was associated with a significant but not minimal important difference (MID) deterioration in disease-specific HRQoL (mean change [95% CI]: CAT +0.74 [0.15 to 1.33]), while no significant change was observed in the generic VAS. Experiencing at least one severe exacerbation also had a significant impact on CAT deterioration (+1.58 [0.52 to 2.64]), but again not on VAS. Here, GOLD groups AB showed not only a statistically but also a clinically relevant MID deterioration in CAT (+2.1 [0.88 to 3.32]). These particular patient groups were further characterized by a higher probability of being male, having a higher mMRC and Charlson index, and a lower probability of having higher FEV1 or BMI values. Conclusion: FEV1 decline and the occurrence of ≥1 severe exacerbation are significantly associated with overall deterioration in disease-specific HRQoL. Preventing severe exacerbations particularly in patients without previous severe exacerbations (ABCD groups A and B) may help to stabilize the key patient-reported outcome HRQoL

Work absenteeism and healthcare utilization in COPD: The clinical cohort COSYCONET compared with population-based controls.

Rationale COPD is a highly prevalent disease and a leading cause of morbidity and mortality. This study investigates COPD-excess work absenteeism and healthcare utilization based on data from the German COSYCONET (“German COPD and Systemic Consequences - Comorbidities Network”) COPD cohort. Methods Self-reported data on work absence and healthcare utilization from 2,288 COPD patients in grade 1 to 4 (GOLD definition, % predicted values according to ECSC) from the COSYCONET cohort was compared with 1,629 controls without COPD from two pooled population-based KORA (“Cooperative Health Research in the Augsburg Region”) studies. Multiple generalized linear models were used to analyze the association of COPD grades with healthcare utilization and work absence while considering differences in sex, age, education, smoking status, BMI and 5 comorbid conditions (stroke, cancer, diabetes, myocardial infarction, and arthritis). Results The total study sample comprised 3,917 participants, mean age 64.3 years, 55.4% males. COPD grade 1-4 significantly increased both the number of physician visits in the last 3 months (all p < 0.0001) and the number of hospital days in the last 12 months (all p <0.005). The adjusted number of physician visits was 2.9 in controls without COPD and 6.2/6.3/6.6/6.3 in COPD grades 1-4. Regarding hospital days, the adjusted number of days increased with COPD disease grade and was 2.5/3.8/7.1/11.3 in grade 1-4 and 1.3 days in controls. Regarding comorbid conditions, an additional diagnosis of cancer or stroke had the largest effect on utilization, but the effects were smaller than the effects of COPD grade 3 or 4. Of those under the age of 65 years (n=2,147), a regular full- or part-time employment was reported by 84% of controls and by 52%/46%/34%/17% of participants in COPD grade 1-4. After adjustment for covariates, the number of sick days in working participants was increased by factor 4.4 in COPD grade 1-3 and by factor 6.8 in grade 4 compared with controls. Resulting adjusted sick days in the last 12 months were 5.9 in controls and 27.4/26.5/28.3/39.0 in GOLD grade 1-4. Cancer or arthritis as an additional condition had increasing effects on sick days, but the effects were smaller than the effect of COPD. Conclusions High healthcare utilization and work absence is observed in COPD patients even in early stages of disease. From a societal perspective, interventions focusing on improving the ability to work in younger COPD patients would be beneficial in order to reduce the indirect costs of COPD

The contribution of symptoms and comorbidities to the economic impact of COPD: An analysis of the German COSYCONET cohort.

Background: Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs. This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD. Methods: Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used. Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement. The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models. Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea. Results: Unadjusted mean annual direct costs were €7,263 per patient. Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%). Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs (p<0.01). A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors. For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs (p<0.04). In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities. Conclusion: Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers. This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD

Utilization and determinants of use of non-pharmacological interventions in COPD: Results of the COSYCONET cohort.

Background: Guidelines for chronic obstructive pulmonary disease (COPD) recommend supplementing pharmacotherapy with non-pharmacological interventions. Little is known about the use of such interventions by patients. We analyzed the utilization of a number of non-pharmacological interventions and identified potential determinants of use.Methods: Based on self-reports, use of interventions (smoking cessation, influenza vaccination, physiotherapy, sports program, patient education, pulmonary rehabilitation) and recommendation to use were assessed in 1410 patients with COPD. The utilization was analyzed according to sex and severity of disease. Potential determinants of utilization included demographic variables and disease characteristics and were analyzed using logistic regression models.Results: Influenza vaccination in the previous autumn/winter was reported by 73% of patients. About 19% were currently participating in a reimbursed sports program, 10% received physiotherapy, 38% were ever enrolled in an educational program, and 34% had ever participated in an outpatient or inpatient pulmonary rehabilitation program. Out of 553 current or former smokers, 24% had participated in a smoking cessation program. While reports of having received a recommendation to use mainly did not differ according to sex, women showed significantly (p < 0.05) higher utilization rates than men for all interventions except influenza vaccination. Smoking was a predictor for not having received a recommendation for utilization and also significantly associated with a reduced odds of utilization. We found a correlation between recommendation to use and utilization.Conclusions: Utilization of non-pharmacological interventions was lower in men and smokers. A recommendation or offer to use by the physician could help to increase uptake