Aim: Advance directives are often under-informed due to a lack of disease-specific prognostic information. Without well-informed advance directives patients may receive default care that is incongruent with their preferences. We aimed to further inform advance care planning in patients with severe chronic obstructive pulmonary disease by estimating outcomes with alternative advance directives. Methods: We designed a Markov microsimulation model estimating outcomes for patients choosing between the Full Code advance directive (permitting invasive mechanical ventilation), and the Do Not Intubate directive (only permitting noninvasive ventilation). Results: Our model estimates Full Code patients have marginally increased one-year survival after admission for severe respiratory failure, but are more likely to be residing in a nursing home and have frequent rehospitalizations for respiratory failure. Conclusion: Patients with severe chronic obstructive pulmonary disease may consider these potential tradeoffs between survival, rehospitalizations and institutionalization when making informed advance care plans and end-of-life decisions. We highlight outcomes research needs for variables most influential to the model‘s outcomes, including the risk of complications of invasive mechanical ventilation and failing noninvasive mechanical ventilation.
Abstract Background Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. Objective To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18–64, 65–79 and ≥ 80 years). Design, setting, and participants Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. Measurements Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. Results The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65–79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members ( p < 0.001 for all age group interactions). Limitations The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. Conclusions Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.
Chronic obstructive pulmonary disease (COPD) prevalence is increasing among aging HIV-infected individuals. We determined the association between COPD and self-reported measures of frailty [adapted frailty-related phenotype (aFRP)] and physical limitation, and a clinical biomarker of physiologic frailty [Veterans Aging Cohort Study (VACS) Index] in HIV-infected compared with uninfected individuals.Cross-sectional study of VACS participants between 2002 and 2012.Prefrail/aFRP was obtained from self-reported surveys. Prefrail was defined as 1-2 domains of physical shrinking, exhaustion, slowness and low physical activity; aFRP was defined as at least 3 domains. Physical limitation scale was determined from 12 self-reported survey items assessing limitations performing physical activities. VACS index includes age and laboratory measurements. We used regression models to test for associations between COPD and outcomes in models stratified by HIV status.The sample included 3538 HIV-infected and 3606 uninfected participants; 67 and 63% were black (P = 0.0003), 97 and 92% were men (P < 0.0001) and 4 and 5% had COPD (P = 0.2). In unadjusted analyses, COPD was associated with all three outcomes (P < 0.0001). In adjusted analyses, COPD was associated with increased prefrail and aFRP in HIV-infected and uninfected participants (P ≤ 0.01 for all comparisons). COPD was associated with physical limitation in both groups (P < 0.0001). There was an interaction between COPD and physical limitation by HIV status with increased physical limitation among HIV-infected participants (P = 0.04). COPD was not associated with VACS index.COPD was strongly associated with aFRP and physical limitations. COPD management may mediate frailty through functional limitations rather than physiologic biomarkers, especially in HIV-infected individuals.
Introduction: Bacterial pneumonia remains an important cause of morbidity and mortality in people living with HIV (PLWH) in the antiretroviral therapy (ART) era. In addition to being immunocompromised, as reflected by low CD4 cell counts and elevated HIV viral loads, PLWH often have other behaviors associated with an increased risk of pneumonia including smoking and injected drug use. As PLWH are aging, comorbid conditions such as chronic obstructive pulmonary disease (COPD), cancers, and cardiovascular, renal and liver diseases are emerging as additional risk factors for pneumonia. Pathogens are often similar to those in HIV-uninfected individuals; however, PLWH are at risk for unusual and/or multi-drug resistant organisms causing bacterial pneumonia based, in part, on their CD4 cell counts and other exposures. Areas covered: In this review, we focus on the recognition and management of bacterial community-acquired pneumonia (CAP) in PLWH. Along with antimicrobial treatment, we discuss prevention strategies such as vaccination and smoking cessation. Expert opinion: Early initiation of ART after HIV infection can decrease the risk of pneumonia. Improved efforts at vaccination, smoking cessation, and reduction of other substance use are urgently needed in PLWH to decrease the risk for bacterial pneumonia. As PLWH are aging, comorbidities are additional risk factors for bacterial CAP.
Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT5-8 microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT5-8 ( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DLCO) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV1 percent predicted and DLCO percent predicted. The MIF-794 CATT5 allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT5 allele was associated with a reduced DLCO percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DLCO, an important measurement of COPD severity.
The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) Community-acquired Pneumonia (CAP) guidelines were developed using systematic reviews to inform every recommendation, as suggested by the Institute of Medicine Standards for Trustworthy Guidelines. Recent studies suggest that an expert consensus-based approach, called the Convergence of Opinion on Recommendations and Evidence (CORE) process, can produce recommendations that are concordant with recommendations informed by systematic reviews.
Rationale: Many advocate the application of propensity-matching methods to real-world data to answer key questions around obstructive sleep apnea (OSA) management. One such question is whether identifying undiagnosed OSA impacts mortality in high-risk populations, such as those with chronic obstructive pulmonary disease (COPD). Objectives: Assess the association of sleep testing with mortality among patients with COPD and a high likelihood of undiagnosed OSA. Methods: We identified patients with COPD and a high likelihood of undiagnosed OSA. We then distinguished those receiving sleep testing within 90 days of index COPD encounters. We calculated propensity scores for testing based on 37 variables and compared long-term mortality in matched groups. In sensitivity analyses, we compared mortality using inverse propensity weighting and instrumental variable methods. We also compared the incidence of nonfatal events including adverse outcomes (hospitalizations and COPD exacerbations) and routine services that are regularly indicated in COPD (influenza vaccination and pulmonary function testing). We compared the incidence of each nonfatal event as a composite outcome with death and separately compared the marginal probability of each nonfatal event independently, with death as a competing risk. Results: Among 135,958 patients, 1,957 (1.4%) received sleep testing. We propensity matched all patients with sleep testing to an equal number without testing, achieving excellent balance on observed confounders, with standardized differences < 0.10. We observed lower mortality risk among patients with sleep testing (incidence rate ratio, 0.88; 95% confidence interval [CI], 0.79–0.99) and similar results using inverse propensity weighting and instrumental variable methods. Contrary to mortality, we found that sleep testing was associated with a similar or greater risk for nonfatal adverse events, including inpatient COPD exacerbations (subhazard ratio, 1.29; 95% CI, 1.02–1.62) and routine services like influenza vaccination (subhazard ratio, 1.26; 95% CI, 1.17–1.36). Conclusions: Our disparate findings can be interpreted in multiple ways. Sleep testing may indeed cause both reduced mortality and greater incidence of nonfatal adverse outcomes and routine services. However, it is also possible that our findings stem from residual confounding by patients' likelihood of accessing care. Given the limitations of propensity-based analyses, we cannot confidently distinguish these two possibilities. This uncertainty highlights the limitations of using propensity-based analyses to guide patient care and policy decisions.
