Chronic obstructive pulmonary disease trajectory: severe exacerbations and dynamic change in health-related quality of life.

BACKGROUND: The life trajectory of chronic obstructive pulmonary disease (COPD) remains unknown. PATIENTS AND METHODS: We collected data from two populations. In the first cohort, we recruited 375 patients with COPD from our hospital, and 1440 repeated assessments of quality of life (QoL) using the European Quality of Life-5 Dimensions questionnaire from 2006 to 2020. We analysed their dynamic changes using the kernel-smoothing method. The second cohort comprised 27 437 patients from the National Health Insurance (NHI) dataset with their first severe acute exacerbations (AEs) requiring hospitalisation from 2008 to 2017 were analysed for their long-term course of AEs. We employed a Cox hazard model to analyse the predictors for mortality or AEs. RESULTS: Cohorts from our hospital and NHI were male predominant (93.6 and 83.5%, respectively). After the first severe AE, the course generally comprised three phases. The first was a 1-year period of elevated QoL, followed by a 2-year prolonged stable phase with a slowly declining QoL. After the second AE, the final phase was characterised by a rapid decline in QoL. For NHI cohort, 2712 died during the 11-year follow-up, the frequency of the first AE was approximately 5 per 10 000 per day. The median time from the first to the second AE was 3 years, which decreased to less than 6 and 3 months from 4th to 5th and 8th to 9th AE, respectively. The frequency of AE was increased 10-fold and 15-fold and risk of subsequent AE was increased 12-fold and 20-fold after the 6th and the 10th AE, relative to the first. Male gender, heart failure comorbidities were associated with the risk of subsequent AE and death. CONCLUSIONS: The life trajectory of COPD includes the accelerated frailty phase, as well as elevated health and prolonged stable phase after the first AE.

Current Progress of COPD Early Detection: Key Points and Novel Strategies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approximately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients.

Mapping algorithms for predicting EuroQol-5D-3L utilities from the assessment test of chronic obstructive pulmonary disease.

To predict 3-Level version of European Quality of Life-5 Dimensions (EQ-5D-3L) questionnaire utility from the chronic obstructive pulmonary disease (COPD) assessment test (CAT), the study attempts to collect EQ-5D-3L and CAT data from COPD patients. Response mapping under a backward elimination procedure was used for EQ-5D score predictions from CAT. A multinomial logistic regression (MLR) model was used to identify the association between the score and the covariates. Afterwards, the predicted scores were transformed into the utility. The developed formula was compared with ordinary least squares (OLS) regression models and models using Mean Rank Method (MRM). The MLR models performed as well as other models according to mean absolute error (MAE) and root mean squared error (RMSE) evaluations. Besides, the overestimation for low utility patients (utility ≤ 0.6) and underestimation for near health (utility > 0.9) in the OLS method was improved through the means of the MLR model based on bubble chart analysis. In conclusion, response mapping with the MLR model led to performance comparable to the OLS and MRM models for predicting EQ-5D utility from CAT data. Additionally, the bubble charts analysis revealed that the model constructed in this study and MRM could be a better predictive model.

Development and validation of a prediction index for recent mortality in advanced COPD patients.

The primary barrier to initiating palliative care for advanced COPD patients is the unpredictable course of the disease. We enroll 752 COPD patients into the study and validate the prediction tools for 1-year mortality using the current guidelines for palliative care. We also develop a composite prediction index for 1-year mortality and validate it in another cohort of 342 patients. Using the current prognostic models for recent mortality in palliative care, the best area under the curve (AUC) for predicting mortality is 0.68. Using the Modified Medical Research Council dyspnea score and oxygen saturation to define the combined dyspnea and oxygenation (DO) index, we find that the AUC of the DO index is 0.84 for predicting mortality in the validated cohort. Predictions of 1-year mortality based on the current palliative care guideline for COPD patients are poor. The DO index exhibits better predictive ability than other models in the study.

The occurrence of and risk factors for developing acute critical illness during quarantine as a response to the COVID-19 pandemic.

BACKGROUND/PURPOSE: Early detection and timely quarantine measures are necessary to control disease spread and prevent nosocomial outbreaks of Coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the impact of a quarantine strategy on patient safety and quality of care. METHODS: This retrospective cohort study enrolled patients admitted to the quarantine ward in a tertiary hospital in southern Taiwan. The incidence and causes of acute critical illness, including clinical deterioration and unexpected complications during the quarantine period, were reviewed. Further investigation was performed to identify risk factors for acute critical illness during quarantine. RESULTS: Of 320 patients admitted to the quarantine ward, more than two-thirds were elderly, and 37.8% were bedridden. During the quarantine period, 68 (21.2%) developed acute critical illness, which more commonly occurred among patients older than 80 years and with a bedridden status, nasogastric tube feeding, or dyspnea symptoms. Bedridden status was an independent predictor of acute critical illness. Through optimization of sampling for COVID-19 and laboratory schedules, both the duration of quarantine and the proportion of acute critical illness among bedridden patients during quarantine exhibited a decreasing trend. There was no COVID-19 nosocomial transmission during the study period. CONCLUSION: The quarantine ward is a key measure to prevent nosocomial transmission of COVID-19 but may carry a potential negative impact on patient care and safety. For patients with multiple comorbidities and a bedridden status, healthcare workers should remain alert to rapid deterioration and unexpected adverse events during quarantine.

Performance and Clinical Utility of Various Chronic Obstructive Pulmonary Disease Case-Finding Tools.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is frequently underdiagnosed because of the unavailability of spirometers, especially in resource-limited outpatient settings. This study provides real-world evidence to identify optimal approaches for COPD case finding in outpatient settings. METHODS: This retrospective study enrolled individuals who were at risk of COPD (age ≥40 years, ≥10 pack-years, and ≥1 respiratory symptom). Eligible participants were examined using various COPD case-finding tools, namely the COPD Population Screener (COPD-PS) questionnaire, a COPD prediction (PCOPD) model, and a microspirometer, Spirobank Smart; subsequently, the participants underwent confirmatory spirometry. The definition and confirmation of COPD were based on conventional spirometry. Receiver operating characteristic curve (ROC), area under the curve (AUC), and decision curve analyses were conducted, and a clinical impact curve was constructed. RESULTS: In total, 385 participants took part in the study [284 without COPD (73.77%) and 101 with COPD (26.23%)]. The microspirometer exhibited a higher AUC value than did the COPD-PS questionnaire and the PCOPD model. The AUC for microspirometry was 0.908 (95% confidence interval [CI] = 0.87-0.95), that for the PCOPD model was 0.788 (95% CI = 0.74-0.84), and that for the COPD-PS questionnaire was 0.726 (95% CI = 0.67-0.78). Decision and clinical impact curve analyses revealed that a microspirometry-derived FEV1/FVC ratio of <74% had superior clinical utility to the other measurement tools. CONCLUSION: The PCOPD model and COPD-PS questionnaire were useful for identifying symptomatic patients likely to have COPD, but microspirometry was more accurate and had higher clinical utility. This study provides real-world evidence to identify optimal practices for COPD case finding; such practices ensure that physicians have convenient access to up-to-date evidence when they encounter a symptomatic patient likely to have COPD.

Effectiveness of Nationwide COPD Pay-for-Performance Program on COPD Exacerbations in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. RESULTS: The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: -2.98%, p<0.05, 95% confidence interval [CI]: -0.277 to -0.086; hospitalization: -1.62%, p<0.05, 95% CI: -0.232 to -0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. CONCLUSION: The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.

Novel App-Based Portable Spirometer for the Early Detection of COPD.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of <0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart; 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860-0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of <74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29-125.75) and old age (OR = 3.23, 95% CI = 1.04-10.07 for 60 ≤ age < 65; OR = 5.82, 95% CI = 2.22-15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

Life expectancy (LE) and loss-of-LE for patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVES: Prognosis of COPD is usually expressed as a 3-year survival rate, which might not be easily understood by lay people. This study estimates the life expectancy (LE) and loss-of-LE for COPD patients with different GOLD stages and patients with a history of acute exacerbation (AE) requiring hospitalization (severe AE) in the preceding year. METHODS: 532 patients who were diagnosed with COPD according to the GOLD criteria at NCKU hospital between 2006 and 2016 were recruited. Survival was estimated by Kaplan-Meier method, and extrapolated to lifetime to obtain the LE. The loss-of-LE was quantified by subtracting the LE of the COPD cohort from national life tables. The survival of patients with severe AE history was validated by a nation-wide cohort from the National Health Insurance dataset. RESULTS: The survival of patients with severe stage COPD (GOLD grades 3 and 4) was almost the same as those patients with a history of severe AE and the loss-of-LE for the former and the latter were 9.3 (1.1) and 9.4 (1.3) years, respectively. The nation-wide cohort with severe AE history (n = 44,764) showed a loss-of-LE of 8.3 (0.1) years. The loss-of-LE of patients with moderate stage COPD (GOLD grade 2) was 6.2 years, but no reduction in LE was noted for mild stage COPD (GOLD grade 1). CONCLUSIONS: We successfully estimated LE and loss of LE in COPD patients under the GOLD criteria. The survival of severe stage COPD patients is almost the same as those with severe AE history, or about 8-9 years of life lost.

Enhanced risk of traumatic brain injury in patients with chronic obstructive pulmonary disease.

This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI).In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. They were subgrouped as 'COPDAE+' (if they had severe acute exacerbation of COPD during the follow-ups) or 'COPDAE-' (if they had no acute exacerbation), and were frequency matched with randomly selected subjects without COPD (the 'non-COPD' group). Baseline differences were balanced by the inverse probability of treatment weighting based on the propensity score. For each patient, the risk of TBI during the subsequent 5 years was determined. The competing risk of death was controlled.We identified 3734 patients in 'COPDAE+', and frequency matched them with 11,202 patients in 'COPDAE-' and 11,202 subjects in 'non-COPD'. Compared with those in 'non-COPD', patients in 'COPDAE+' and 'COPDAE-' had an increased risk of TBI: the adjusted HR for 'COPDAE+' was 1.50, 95% CI 1.31 to 1.73, and that for 'COPDAE-' was 1.21, 95% CI 1.09 to 1.34. The highest risk was observed in the 'COPDAE+' group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64).COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI.

Validation of the GOLD 2017 and new 16 subgroups (1A-4D) classifications in predicting exacerbation and mortality in COPD patients.

BACKGROUND AND OBJECTIVE: A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017. We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications. METHODS: Patients with COPD were recruited from January 2006 to December 2017. The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC). RESULTS: A total of 553 subjects with COPD were analyzed. The mortality rate was 48.6% during a median follow-up period of 5.2 years. Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively. The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively. Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively). The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001). CONCLUSION: The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients. Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality. SUMMARY AT A GLANCE: We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients. The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor. The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients.

Population-based cohort study suggesting a significantly increased risk of developing chronic obstructive pulmonary disease in people with type 2 diabetes mellitus.

AIMS: To investigate whether type 2 diabetes mellitus (T2DM) increases the risk of developing chronic obstructive pulmonary disease (COPD). METHODS: This population-based cohort study used Taiwan's National Health insurance claim data to investigate the association of T2DM with the risk of COPD. A total of 716,623 pairs of people (patients with T2DM and their age-, sex-, and calendar year-matched controls) were identified in 2002-2003 and were followed until the occurrence of newly-diagnosed COPD or the end of 2011. Cox proportional hazard models were used to relate COPD incidence to T2DM. RESULTS: People with T2DM experienced a higher incidence rate of COPD than controls (159.6 vs 122.7 per 104 person-years). After controlling for confounders, T2DM significantly increased the hazard of COPD (hazard ratio [HR] = 1.15, 95% confidence interval = 1.14-1.16). Stratified analysis indicated that the association between T2DM and COPD was slightly greater in women than in men (HR, 1.15 vs. 1.11) and in people aged <65 years than in people aged ≥65 years (HR, 1.17 vs. 1.05 in men; 1.16 vs. 1.13 in women). CONCLUSIONS: Our findings demonstrated a modest association of T2DM with the risk of developing COPD, possibly shedding light into the adverse effects of hyperglycemia on pulmonary function.

Comparison of different staging methods for COPD in predicting outcomes.

Chronic obstructive pulmonary disease (COPD) is commonly staged according to the percentage of predicted forced expiratory volume in 1 s (FEV1 % pred), but other methods have been proposed. In this study we compared the performance of seven staging methods in predicting outcomes.We retrospectively studied 296 COPD outpatients. For each patient the disease severity was staged by separately applying the following methods: the criteria proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), quartiles of FEV1 % pred and z-score of FEV1, quartiles and specified cut-off points of the ratio of FEV1 over height squared ((FEV1·Ht-2)A and (FEV1·Ht-2)B, respectively), and quartiles of the ratio of FEV1 over height cubed (FEV1·Ht-3) and of FEV1 quotient (FEV1Q). We evaluated the performance of these methods in predicting the risks of severe acute exacerbation and all-cause mortality.Overall, staging based on the reference-independent FEV1Q performed best in predicting the risks of severe acute exacerbation (including frequent exacerbation) and mortality, followed by (FEV1·Ht-2)B The performance of staging methods could also be influenced by the choice of cut-off values. Future work using large and ethnically diverse populations to refine and validate the cut-off values would enhance the prediction of outcomes.

Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort.

OBJECTIVE: Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma. METHODS: We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856). We also used a case-control study nested from the above cohort including 1,982 incident cases of asthma and 1,982 age- and sex-matched controls. A time density sampling technique was used to assess the effects of various antidiabetic agents on the risk of asthma. RESULTS: The incidence of asthma was significantly higher in the diabetic cohort than that in the non-diabetic cohort after adjustment for age, sex, and obesity, with a hazard ratio of 1.30 (95% confidence interval [CI]: 1.24-1.38). Insulin was found to increase the risk of asthma among diabetic patients (odds ratio [OR] 2.23; 95% CI: 1.52-3.58). In contrast, the use of metformin correlated with a decreased risk of asthma (OR 0.75; 95% CI: 0.60-0.95). CONCLUSIONS: Individuals with diabetes are at an increased risk of asthma. Insulin may further increase the risk of asthma, but the risk could possibly be reduced by using metformin.

Validation of the GOLD 2013 classification in predicting exacerbations and mortality in Taiwanese patients with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Evidence for the effectiveness of the new multidimensional GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification is currently limited. The new classification has been validated in the United States and Europe, but validation in Asian patients is still lacking. We examined the abilities of the GOLD 2013 classification to predict clinical outcomes in Taiwanese patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD were recruited from January 2006 to December 2012 and followed up for exacerbation and mortality. The predictive abilities of various assessments were compared through logistic regression analysis using receiver operating curve (ROC) estimations and area under the curve (AUC). RESULTS: A total of 471 patients with COPD were analyzed. The GOLD 2013 groups at high risk of exacerbation (C and D) experienced a higher average number of exacerbations per year (2.1 ± 3.1 vs. 0.3 ± 1.0, p < 0.001) than the low risk groups (A and B). The mortality rates were 10.1% in GOLD 2013 Group A, 14.1% in Group B, 4.0% in Group C, and 30.5% in Group D. The AUC values for GOLD 2013 and GOLD 2007 were 0.78 versus 0.67 (p < 0.001) for exacerbation, and 0.66 versus 0.61 (p = 0.15) for mortality. CONCLUSION: The GOLD 2013 classification has powerful ability to predict exacerbation, but poor ability to predict mortality. The prognostic validity of the GOLD 2013 classification to predict exacerbations was better than the GOLD 2007 classification.

Comparison of global initiative for chronic obstructive pulmonary disease 2013 classification and body mass index, airflow obstruction, dyspnea, and exacerbations index in predicting mortality and exacerbations in elderly adults with chronic obstructive pulmonary disease.

OBJECTIVES: To examine whether the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) 2013 revision offers greater predictive ability than the body mass index, airflow obstruction, dyspnea, and exacerbations (BODEx) index in elderly adults with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cohort study. SETTING: University-affiliated medical center. PARTICIPANTS: Taiwanese outpatients with COPD (N = 354). MEASUREMENTS: Participants were classified as Group A (low risk with mild dyspnea), Group B (low risk with more-severe dyspnea), Group C (high risk with mild dyspnea), and Group D (high risk with more-severe dyspnea) for GOLD 2013 and from Quartile 1 (0-2 points) to 4 (7-9 points) for BODEx score. Ability to predict exacerbations and mortality was compared using logistic regression analysis with receiver operating characteristic (ROC) curve estimations and area under the ROC curve (AUC). RESULTS: Mortality was 14.1% for GOLD Group A, 14.5% for Group B, 6.5% for Group C, and 35.8% for Group D and 15.2% for BODEx Quartile 1, 22.5% for Quartile 2, 28.1% for Quartile 3, and 79.2% for Quartile 4. Risk of exacerbation relative to Group A was 1.7 (95% confidence interval (CI) = 0.6-4.3) for Group B, 14.1 (95% CI = 4.6-43.2) for Group C, and 17.9 (95% CI = 7.6-42.0) for Group D. The AUC for the GOLD classification and BODEx index were 0.65 and 0.67 for mortality (P = .60) and 0.79 and 0.73 for exacerbation (P = .03). CONCLUSION: The GOLD 2013 classification performed well in identifying individuals at risk of exacerbations, and its predictive ability for exacerbations was better than that of the BODEx index, although the predictive ability for mortality in elderly adults with COPD was poor for both indices.

Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population.

BACKGROUND AND OBJECTIVE: Although surfactant protein-D (SP-D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP-D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP-D are associated with COPD-related phenotypes and disease prognosis. METHODS: A hospital-based, case-controlled study was conducted prospectively. Six single nucleotide polymorphisms of the SFTPD gene were determined for genetic association analysis. Inflammatory cytokines and SP-D serum level were quantified. Frequency of exacerbation and change of lung function were assessed. All-cause 3-year mortality was registered. RESULTS: We studied 320 smokers (192 with COPD and 128 at-risk for COPD) who were prospectively monitored for at least 3 years. The serum levels of SP-D in COPD patients were significantly associated with the degree of airflow obstruction and frequency of exacerbation. Haplotype association analysis revealed that haplotype G-G-C-C-A was associated with lower risk of COPD (P = 0.03) in our study population. COPD patients with haplotype G-G-C-C-A had lower serum SP-D levels (P < 0.001), higher rates of positive response to bronchodilator treatment (P = 0.01), more improvement of forced expiratory volume in 1 s in yearly follow-up (P = 0.03) and better 3-year survival rate than COPD patients with non G-G-C-C-A haplotype (P = 0.03). CONCLUSIONS: Genetic haplotype of SP-D may serve as a valuable prognostic indicator in Chinese patients with COPD.

Association of Egr-1 and autophagy-related gene polymorphism in men with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Autophagy is important in cellular homeostasis and control of inflammatory immune response. Increased autophagy has recently been associated with increased cell death and chronic obstructive pulmonary disease (COPD) pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early growth response), associated with different phenotype expressions in asthma; and, Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for susceptibility to chronic inflammatory diseases. We will explore the role of the Egr-1 and Atg16L1 gene polymorphisms in COPD. METHODS: The genotypes of 151 male smoking patients with COPD and 100 male smoking controls were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the Egr-1 (-4071 A → G) rs7729723 and Atg16L-1 (T300A) rs2241880 variants. RESULTS: The G allele of the Egr-1 gene polymorphism was associated with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0% (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI, 1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151) vs. 81.0% (81/100); p = 0.013]. CONCLUSION: The Egr-1 and Atg16L1 genes' polymorphisms were significant risk factors for susceptibility to COPD. These results demonstrate that autophagy regulator genetic mutations are associated with COPD in male smokers.

Using cluster analysis to identify phenotypes and validation of mortality in men with COPD.

PURPOSE: Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. METHODS: Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV(1) % predicted, BMI, history of severe exacerbations, mMRC, SpO(2), and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. RESULTS: Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. CONCLUSION: COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.