External Validation of the COmorbidity Test.

The COmorbidity TEst (COTE) is a Chronic Obstructive Pulmonary Disease (COPD)-specific co-morbidity score created to predict mortality. Before its wide application at the University of New Mexico we intended to validate it. The study was conducted at the University of New Mexico Hospital (UNMH) in Albuquerque, NM, USA, a tertiary academic hospital. Consecutive patients with the clinical diagnosis of COPD were identified using the hospital's medical records system and included if they were older than 40 years, had smoked at least 20 pack-years and their post bronchodilator forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) was <0.7 without an alternative diagnosis. The data collected included demographics, co-morbidities as described in the COTE, COPD-specific therapies, spirometry results and mortality. Of 317 patients 51.4% were male, average age was 65.6 ± 9.6 years and the mean post-bronchodilator FEV1 percent predicted (FEV1%) was 52.9 ± 16.9%. 31 (9.8%) patients were on triple long-acting bronchodilator inhaler therapy, 88 (27.8%) on two long-acting bronchodilators and 163 (51.4%) on at least one long-acting bronchodilator. The median follow-up was 3.5 years (IQR = 1.9-6.9). Fifty four patients died by the end of the follow-up period and their median COTE of 4 (IQR = 1-8) was significantly higher than for the survivors with COTE = 1 (IQR = 0-6; p = 0.002). In univariable analyses COTE was positively associated while FEV1%, body mass index (BMI) and gender were negatively associated with all-cause mortality. In multivariable analysis BMI, FEV1% and COTE remained independent predictors for mortality. The COTE is an independent predictor of mortality for COPD patients at UNMH.

Chronic obstructive pulmonary disease mortality, a competing risk analysis.

BACKGROUND: Current risk factors for Chronic Obstructive Pulmonary Disease mortality focus only on overall and respiratory death. We investigated whether risk factors for each specific cause of mortality are different depending on the outcome under consideration. METHODS: This retrospective cohort study included patients with a clinical diagnosis of COPD, older than 40, greater than 20 pack-years smoking history, and obstructive pattern on spirometry. Collected data included baseline spirometry, comorbidities, medication use, tobacco exposure, severe exacerbations, and cause-specific mortality. RESULTS: This 512 patient cohort of heavy smokers included 277 (54.1%) males, was on average 66.4 ± 9.4 years of age and primarily non-Hispanic white, 395 (83.2%). The average FEV1% was 52.1% (SD = 16.9%) and the median COTE score was 2 (IQR: 0-6). A total of 67 deaths were of respiratory causes in 26 patients (38.8%), malignancies in 21 (31.1%), cardiovascular causes in 6 (9%), and from other etiologies in 14 patients (20.1%). COTE index,low predicted FEV1%, and lower body mass index were significant predictors of overall mortality. Predictors of respiratory deaths were significantly impacted by lower FEV1%, history of COPD exacerbations, lower BMI, and higher number of pack-years smoked. Risk factors for all other cause-specific mortality combined included history of malignancy or cardiovascular disease and smoking status. CONCLUSION: Cause-specific mortality risk factors differ in patients with COPD.

Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques.

In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent among PLWH, HIV may be an independent risk factor for lung diseases; however, the role of HIV and cigarette smoke (CS) and their potential interaction in the development of chronic lung diseases among PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and treated with cART. The development of CB and the lung functions were evaluated following CS±SHIV treatment. The results showed that in the lung, SHIV was a strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus formation, MUC5AC synthesis, loss of tight junction proteins, and increased expression of Th2 cytokines/transcription factors. In addition, SHIV and CS synergistically reduced lung function and increased extrathoracic tracheal ring thickness. Interestingly, SHIV infection generated significant numbers of HIV-gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV independently induces CB and pro-COPD changes in the lung, and the effects are exacerbated by CS.