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Background: In the United States, COPD is a leading cause of mortality, with a substantial societal health and economic burden. With anticipated population growth, it is important for various stakeholders to have an estimate for the projected burden of disease., Research Question: The goal of this study was to model the 20-year health and economic burden of COPD, from 2019 to 2038, in the United States., Study Design and Methods: Using country-specific data from published literature and publicly available datasets, a dynamic open cohort Markov model was developed in a probabilistic Monte Carlo simulation. Population growth was modeled across different subgroups of age, sex, and smoking. The COPD prevalence rates were calibrated for different subgroups, and distributions of severity grades were modeled based on smoking status. Direct costs, indirect absenteeism costs, losses of quality-adjusted life years (QALYs), and number of exacerbations and deaths associated with COPD were projected., Results: The 20-year discounted direct medical costs attributable to COPD were estimated to be $800.90 billion (95% credible interval [CrI], 565.29 billion-1,081.29 billion), with an expected $337.13 billion in male subjects and $463.77 billion in female subjects. The 20-year discounted indirect absenteeism costs were projected to be $101.30 billion (70.82 billion-137.41 billion). The 20-year losses of QALYs, number of exacerbations, and number of deaths associated with COPD were 45.38 million (8.63 million-112.07 million), 315.08 million (228.59 million-425.33 million), and 9.42 million (8.93 million-9.93 million), respectively. The proportion of disease burden attributable to continued smoking was 34% in direct medical costs, 35% in indirect absenteeism costs, and 37% in losses of QALYs over 20 years., Interpretation: This study projects the substantial burden of COPD that the American society is expected to incur with current patterns for treatments and smoking rates. Mitigating such burden requires targeted budget appropriations and cost-effective interventions., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations., Research Question: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD., Study Design and Methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status., Results: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001., Interpretation: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD., Methods: Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with either azithromycin or placebo for 12 months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13 months, during which time health status and exacerbations were carefully ascertained, and an additional 29 months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff., Results: Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (β = -0.09, P = .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P = .002) and the risk of mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P = .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P = .008 for exacerbation and interaction P = .017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The BMI, obstruction, dyspnea, and exercise capacity (BODE) score is used to inform prognostic considerations for lung transplantation for COPD, but it has not been validated in this context. A large proportion of mortality in COPD is attributable to comorbidities that could preclude transplant candidacy. We hypothesized that patients with COPD who are selected as transplant candidates experience better survival than traditional interpretation of BODE scores might indicate., Methods: We performed a retrospective analysis of survival according to the BODE score for patients with COPD in the United Network of Organ Sharing (UNOS) database of lung transplantation candidates (n = 4,377) compared with the cohort of patients with COPD in which the BODE score was validated (n = 625)., Results: Median survival in the fourth quartile of BODE score was 59 months (95% CI, 51-77 months) in the UNOS cohort and 37 months (95% CI, 29-42 months) in the BODE validation cohort. In models controlling for BODE score and incorporating lung transplantation as a competing end point, the risk of death was higher in the BODE validation cohort (subhazard ratio, 4.8; 95% CI, 4.0-5.7; P < .001). The risk difference was greatest in the fourth quartile of BODE scores (SHR, 6.1; 95% CI, 4.9-7.6; P < .001)., Conclusions: Extrapolation of prognosis based on the BODE score overestimates mortality risk in lung transplantation candidates with COPD. This is likely due to a lower prevalence of comorbid conditions attributable to the lung transplantation evaluation screening process., (Published by Elsevier Inc.)

In emphysema airway resistance can exceed collateral airflow resistance, causing air to flow preferentially through collateral pathways. In severe emphysema ventilation through openings directly through the chest wall into the parenchyma (spiracles) could bypass airway obstruction and increase alveolar ventilation via transpleural expiration. During lung transplant operations, spiracles occasionally can occur inadvertently. We observed transpleural expiration via spiracles in three subjects undergoing lung transplant for emphysema. During transpleural spiracle ventilation, inspiratory tidal volumes (TV) were unchanged; however, expiration was entirely transpleural in two patients whereas the expired TV to the ventilator circuit was reduced to 25% of the inspired TV in one. At baseline, mean PCO2 was 61 ± 5 mm Hg, which decreased to a mean PCO2 of 49 ± 5 mm Hg (P = .05) within minutes after transpleural spiracle ventilation and further decreased at 1 to 2 h (36 ± 4 mm Hg; P = .002 compared with baseline) on unchanged ventilator settings. This observation of increased alveolar ventilation supports further studies of spiracles as a possible therapy for advanced emphysema., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil., Methods: A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC / recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio ≤ 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function., Results: The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 ± 0.13 vs 0.89 ± 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV(1)/FVC ratios (0.895 ± 0.13 vs 0.821 ± 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 ± 0.2 vs 0.64 ± 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% ± 17.1% vs 65.3% ± 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome (BOS) showed that patients in the oversized cohort had a lower probability of BOS (P < .001)., Conclusions: A pTLC ratio > 1.0, suggestive of an oversized allograft, is associated with higher expiratory airflow capacity and a less frequent occurrence of BOS.