Review of the Evidence for Pulmonary Rehabilitation in COPD: Clinical Benefits and Cost-Effectiveness.

COPD is a common and lethal chronic condition, recognized as a leading cause of death worldwide. COPD is associated with significant morbidity and disability, particularly among older adults. The disease course is marked by periods of stability and disease exacerbations defined by worsening respiratory status resulting in a high burden of health care utilization and an increased risk of mortality. Treatment is focused on pharmacologic therapies, but these are not completely effective. Pulmonary rehabilitation (PR) represents a key medical intervention for patients with chronic respiratory diseases, including COPD. PR provides individualized and progressive exercise training, education, and self-management strategies through a comprehensive and multidisciplinary program. PR has been associated with improvement in exercise capacity, health-related quality of life, and dyspnea in patients living with COPD. Moreover, PR has been associated with improvements in hospital readmission and 1-y survival. In addition to the clinical benefits, PR is estimated to be a cost-effective medical intervention. Despite these benefits, participation in PR remains low. We will review the evidence for PR in each of these benefit domains among patients with stable COPD and in those recovering from a COPD exacerbation.

Risk of Atherosclerotic Cardiovascular Disease Hospitalizations after COPD Hospitalization among Older Adults.

BACKGROUND: Meta-analyses have suggested the risk of atherosclerotic cardiovascular disease (ASCVD) events is significantly higher after a chronic obstructive pulmonary disease (COPD) exacerbation. However, these studies have been limited to highly selected patient populations potentially not generalizable to the broader population of COPD. METHODS: We assessed the risk of ASCVD hospitalizations after COPD hospitalization compared to before COPD hospitalization and identified patient factors associated with ASCVD hospitalizations after COPD hospitalization. This retrospective cohort study used claims data from 920,550 Medicare beneficiaries hospitalized for COPD from 2016-2019 in the US. The primary outcome was risk of a ASCVD hospitalization composite outcome (myocardial infarction, percutaneous coronary intervention, coronary artery by-pass graft surgery, stroke, or transient ischemic attack) in the 1 year after-COPD hospitalization relative to the 1 year before-COPD hospitalization. Time from discharge to a composite ASCVD hospitalization outcome was modeled using an extension of the Cox Proportional-Hazards model, the Anderson-Gill model with adjustment for patient characteristics. Additional analyses evaluated for interactions in subgroups and risk factors associated with the composite ASCVD hospitalization outcome. RESULTS: Among 920,550 patients (mean age, 73 years) the hazard ratio estimate (HR; 95% CI) for the composite ASCVD hospitalization outcome after-COPD hospitalization vs before-COPD hospitalization was 0.99 (0.97, 1.02; p = 0.53) following adjustment. We observed 3 subgroups that were significantly associated with higher risk for ASCVD hospitalizations after COPD hospitalization: 76+ years old, women, COPD hospitalization severity. Among the 19 characteristics evaluated, 10 were significantly associated with higher risk of CVD events 1 year after COPD hospitalization with hyperlipidemia (2.78; 2.67, 2.90) and history of cardiovascular disease (1.77; 1.72 1.83) associated with the greatest risk. CONCLUSION: Among Medicare beneficiaries hospitalized for COPD, the risk of ASCVD hospitalizations was not significantly increased after COPD-hospitalization relative to before-COPD hospitalization. Although, we identified age 76+ years old, female sex, and COPD hospitalization severity as high risk subgroups and 10 risk factors associated with increased risk of ASCVD events after-COPD hospitalization. Further research is needed to characterize the COPD exacerbation populations at highest ASCVD hospitalization risk.

Timing of Treatment Outcomes and Risk Factors for Failure of BPAP in Patients Hospitalized for COPD Exacerbation.

BACKGROUND: Patients hospitalized for COPD exacerbation have an increased risk of mortality, particularly among those who fail bi-level positive airway pressure (BPAP) for hypercapnic respiratory failure subsequently requiring invasive mechanical ventilation. Therefore, we sought to investigate the treatment course of BPAP and factors associated with BPAP treatment failure. METHODS: We performed a retrospective cohort study using real-world evidence to investigate subjects with COPD who were treated with BPAP during a hospitalization for COPD exacerbation. Treatment outcomes were defined within 7 d from BPAP initiation as either failure, persistent, or success. Failure was defined as death or progression to invasive ventilation. Persistent was defined as receiving BPAP during hospital day 7. Success was defined as liberation from BPAP prior to hospital day 7 and not meeting criteria for failure. Unadjusted multinomial logistic regression models were used to examine the association between BPAP treatment outcomes and 17 recipient characteristics. RESULTS: Among the 427 clinical encounters, 78% were successful, 10% were persistent, and 12% experienced failure. The median time to failure and success was 8 h and 16 h, respectively. Increasing age, body mass index (BMI), bicarbonate level, and creatinine level were significantly associated with either BPAP treatment failure, persistent treatment, or both. CONCLUSIONS: The first 8 h following initiation of BPAP is a critical time period where patients are at high risk for life-threatening decompensation. Careful consideration should be given to increasing age, BMI, bicarbonate level, and creatinine level as these factors were associated with BPAP treatment failure or persistent treatment.

Cost-effectiveness of Pulmonary Rehabilitation Among US Adults With Chronic Obstructive Pulmonary Disease.

Importance: Pulmonary rehabilitation (PR) after exacerbation of chronic obstructive pulmonary disease (COPD) is effective in reducing COPD hospitalizations and mortality while improving health-related quality of life, yet use of PR remains low. Estimates of the cost-effectiveness of PR in this setting could inform policies to improve uptake. Objective: To estimate the cost-effectiveness of participation in PR after hospitalization for COPD. Design, Setting, and Participants: This economic evaluation estimated the cost-effectiveness of participation in PR compared with no PR after COPD hospitalization in the US using a societal perspective analysis. A Markov microsimulation model was developed to estimate the cost-effectiveness in the US health care system with a lifetime horizon, 1-year cycle length, and a discounted rate of 3% per year for both costs and outcomes. Data sources included published literature from October 1, 2001, to April 1, 2021, with the primary source being an analysis of Medicare beneficiaries living with COPD between January 1, 2014, and December 31, 2015. The analysis was designed and conducted from October 1, 2019, to December 15, 2021. A base case microsimulation, univariate analyses, and a probabilistic sensitivity analysis were performed. Interventions: Pulmonary rehabilitation compared with no PR after COPD hospitalization. Main Outcomes and Measures: Net cost in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Results: Among the hypothetical cohort with a mean age of 76.9 (age range, 60-92) years and 58.6% women, the base case microsimulation from a societal perspective demonstrated that PR resulted in net cost savings per patient of $5721 (95% prediction interval, $3307-$8388) and improved quality-adjusted life expectancy (QALE) (gain of 0.53 [95% prediction interval, 0.43-0.63] years). The findings of net cost savings and improved QALE with PR did not change in univariate analyses of patient age, the Global Initiative for Obstructive Lung Disease stage, or number of PR sessions. In a probabilistic sensitivity analysis, PR resulted in net cost savings and improved QALE in every one of 1000 samples and was the dominant strategy in 100% of simulations at any willingness-to-pay threshold. In a 1-way sensitivity analysis of total cost, assuming completion of 36 sessions, a single PR session would remain cost saving to $171 per session and had an incremental cost-effectiveness ratio of $884 per session for $50 000/QALY and $1597 per session for $100 000/QALY. Conclusions and Relevance: In this economic evaluation, PR after COPD hospitalization appeared to result in net cost savings along with improvement in QALE. These findings suggest that stakeholders should identify policies to increase access and adherence to PR for patients with COPD.

Risk factors for mortality in lung transplant recipients aged ≥65 years: A retrospective cohort study of 5,815 patients in the scientific registry of transplant recipients.

BACKGROUND: Lung transplantation is increasingly performed in recipients aged ≥65 years. However, the risk factors for mortality specific to this population have not been well studied. In lung transplant recipients aged ≥65 years, we sought to determine post-transplant survival and clinical factors associated with post-transplant mortality. METHODS: We investigated 5,815 adult lung transplants recipients aged ≥65 years in the Scientific Registry of Transplant Recipients. Mortality was defined as a composite of recipient death or retransplantation. The Kaplan-Meier method was used to estimate the median time to mortality. Univariable and multivariable Cox proportional hazards regression models were used to examine the association between time to mortality and 23 donor, recipient, or center characteristics. RESULTS: Median survival in lung transplant recipients aged ≥65 years was 4.41 years (95% CI: 4.21-4.60 years) and significantly worsened by increasing age strata. In the multivariable model, increasing recipient age strata, creatinine level, bilirubin level, hospitalization at the time of transplantation, single lung transplant operation, steroid use at the time of transplantation, donor diabetes, and cytomegalovirus mismatch were independently associated with increased mortality. CONCLUSIONS: Among the 8 risk factors we identified, 5 factors are readily available, which can be used to optimize post-transplant survival by informing risk during candidate selection of patients aged ≥65 years. Furthermore, bilateral lung transplantation may confer improved survival in comparison with single lung transplantation. Our results support that after careful consideration of risk factors, lung transplantation can provide life-extending benefits in individuals aged ≥65 years.

Cardiovascular implications of idiopathic pulmonary fibrosis: A way forward together?

Cardiovascular disease has an increased prevalence among patients with idiopathic pulmonary fibrosis (IPF). Cardiovascular disease and IPF share similar symptoms with overlapping demographics and risk factors for disease development. Common cellular mediators leading to disease development and progression have been identified in both the cardiovascular and pulmonary organ systems. In this context, discovery of new therapeutic targets and medical therapies could be mutually beneficial across cardiopulmonary diseases. Here we present (1) a clinical review of IPF for the cardiovascular clinician and (2) common cellular mechanisms responsible for fibrosis in the heart and lungs and (3) highlight future research considerations and the potential role of novel therapeutic agents which may be mutually beneficial in cardiac and pulmonary fibrosis.