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.

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.

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.

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.

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.

Health-related quality of life after first-line anti-cancer treatments for advanced non-small cell lung cancer in clinical practice.

PURPOSE: This study attempted to compare changes in the Quality-of-Life (QoL) scores after three different first-line anti-cancer treatments for advanced non-small cell lung cancer (NSCLC) in a real-world clinical setting. PATIENTS AND METHODS: From May 2011 to December 2013, we prospectively measured the QoL scores of patients with locally advanced or metastatic NSCLC using the World Health Organization Quality-of-Life-Brief (WHOQOL-BREF) questionnaire. Each QoL measurement was matched by age and sex with one healthy referent from the National Health Interview Survey. Dynamic changes in patients' QoL scores and major determinants were repeatedly assessed by construction of a mixed-effects model to adjust for possible confounders. RESULTS: A total of 336 patients with 577 QoL measurements related to first-line anti-cancer treatments were enrolled. Performance status was the most important predictor of QoL scores in all domains after controlling for potential confounders. With age- and sex-matched healthy subjects as the reference, patients treated with gemcitabine + platinum showed significantly lower scores in multiple physical and psychological domain items in the WHOQOL-BREF. However, pemetrexed + platinum and gefitinib/erlotinib affected patients' QoL scores in 'energy/fatigue' and 'daily activities' with smaller magnitudes, and the scores appeared to improve after 3-4 months of treatment. CONCLUSIONS: Patients receiving gemcitabine + platinum as first-line anti-cancer treatment for advanced NSCLC experienced relatively poor QoL scores throughout treatment course. Studies to develop a real-time computerized system automatically updating the mixed-effects model for QoL to facilitate participatory clinical decision making by physicians, patients, and their families merit further research.

Different Severity and Severity Predictors in Early-Onset and Late-Onset Asthma: A Taiwanese Population-Based Study.

BACKGROUND: Late-onset asthma has been shown to be more severe than early-onset asthma in clinic-based studies. However, population-based studies are scarce, and the predictors of severity have been less studied. OBJECTIVES: To determine asthma severity and severity predictors regarding age at onset. METHODS: A cross-sectional questionnaire survey was conducted among parents of children from 94 schools in Taiwan in 2004. Asthma severity was defined as short-acting ß2-agonist (SABA), inhaled corticosteroid (ICS) and health care use in the last year. Information on age at onset, demographics, heredity and home exposure was collected. Ordered logistic or logistic regression was used for determining the associations between risk factors and severity. RESULTS: Participants aged 26-50 years were included, resulting in 21,057 (67.8%) participants. Among them, 449 reported ever having had physician-diagnosed asthma, and 381 of those subjects answered the question on age at asthma onset. The risks of rescue SABA, ICS and health care use were generally higher among late-onset (13-50 years) than early-onset (0-12 years) asthmatics. Use of SABA and health care increased from childhood-onset, adolescent- or young adult-onset to adult-onset asthma. Allergic rhinitis was positively associated with SABA use (OR, 9.08; 95% CI, 1.06-77.99) and ICS use (OR, 5.08; 95% CI, 1.47-17.52) in early-onset asthma. Dehumidifier use was negatively associated with SABA use (OR, 0.50; 95% CI, 0.29-0.87) and ICS use (OR, 0.38; 95% CI, 0.19-0.78) in late-onset asthma. CONCLUSIONS: In adults, late-onset asthma was more severe than early-onset asthma. Severity, as indicated by SABA and ICS use, was positively associated with allergic rhinitis in early-onset asthma and negatively associated with dehumidifier use in late-onset asthma.

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.

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.

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.

Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.

BACKGROUND: In western countries, late-onset asthmatics are more severe than early-onset asthmatics in clinic-based studies. However, whether asthma occurrence rates were higher in late ages than in younger ages was inconclusive. This information is essentially lacking in Asian population. METHODS: The participants were schoolchildren's parents recruited from 94 elementary and middle schools in 2004. A cross-sectional self-administered questionnaire was sent through the children to their parents to survey their respiratory health. We investigated typical asthma symptoms occurring at different ages and subsequent remission or relapse after the first asthma event. Person-years of the participants from birth to the time of survey were used as the denominator. RESULTS: Among the 25,377 participants consisting of 949,807 total person-years, 860 reported ever having asthma. Highest incidences occurred at ages 0-12 and 36-40 years. The incidence of asthma was higher in males before puberty, and higher in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person-years for females and males, respectively. Participants with late-onset asthma (onset age >12 years) comprised a large portion of adult current asthmatics. More than 52% of persistence or relapse was observed in early-onset asthma (onset age ≤12 years). The younger birth cohort had a more prominent later peak of asthma incidence than the older one. CONCLUSIONS: In Asian population, asthma occurrence showed a U-shape age distribution with a prominent second peak in the thirties. A high proportion of early-onset asthma relapsed and most of late-onset asthma persisted or relapsed in adulthood.

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.

Discriminative and predictive properties of multidimensional prognostic indices of chronic obstructive pulmonary disease: a validation study in Taiwanese patients.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a pulmonary disease with systemic involvement. Several multidimensional indices have been developed to predict long-term outcomes. However, these indices have not been compared and validated in Taiwanese patients with COPD. METHODS: A prospective, observational, hospital-based study was designed, and a total of 621 patients were recruited from May 2006 to December 2011. Patients followed at least 1 year were enrolled and 594 patients eligible for inclusion. Three prognostic indices--the ADO (age, dyspnoea and airflow obstruction), BODEx (body mass index, airflow obstruction, dyspnoea and exacerbations), and CPI (the COPD Prognostic Index)--were validated and the predictive power of each was analysed. RESULTS: The median follow-up of the 594 patients was 33 months (range 1-72 months), and the mortality rate was 19.2% (114 deaths). All indices were significantly predictive for all-cause mortality in our validation cohort. Furthermore, the C statistics of the three indices, indicating their predictive accuracy, were all >0.7 (area under the curve of the CPI 0.718, P < 0.001, ADO 0.702, P < 0.001, BODEx 0.702, P < 0.001). CONCLUSIONS: ADO, BODEx and CPI scores are useful predictors of all-cause mortality with significantly discriminative properties in Taiwanese patients with COPD.

Pulmonary function change in patients with Sauropus androgynus-related obstructive lung disease 15 years later.

BACKGROUND/PURPOSE: Little is understood about the clinical course and prognosis of patients with Sauropus androgynus-related obstructive lung disease. The aim of this study was to investigate their clinical manifestations and pulmonary function change 15 years after the acute episode. METHODS: A descriptive, observational study of patients with S androgynus-related obstructive lung disease, diagnosed 15 years ago, was conducted. We evaluated their pulmonary function and the Modified Medical Research Council (MMRC) dyspnea scale. Saint George's Respiratory Questionnaire (SGRQ) was also performed. Age- and forced expiratory volume in one second (FEV1)-matched chronic obstructive pulmonary disease (COPD) patients were used as a reference group for comparison of clinical manifestations. RESULTS: Twenty-nine of 49 patients, diagnosed at our hospital 15 years ago, could be contacted. Four patients died and one patient was ventilator-dependent. Sixteen patients were willing to come to our hospital to have pulmonary function and questionnaire evaluation. The FEV1 of these patients declined only 1.6 ± 21.6 mL/year over a 15-year period. Meanwhile, the severity of their dyspnea and their health-related quality of life were better than age- and FEV1-matched COPD patients as shown by the MMRC dyspnea scale (1.4 ± 0.8 vs. 2.0 ± 1.0; p = 0.037) and symptom domain of the SGRQ (32.6 ± 18.4 vs. 43.5 ± 20.3; p = 0.006). CONCLUSION: After an acute deterioration, patients with S androgynus-related obstructive lung disease had a stationary pulmonary function over a period of 15 years, and their clinical manifestations were less severe than age- and FEV1-matched COPD patients. A further study with a larger sample size may be needed to confirm these findings.

The role of bactericidal/permeability-increasing protein in men with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system. Recently, an association between genetic polymorphism in the BPI gene and a risk of airflow decline after transplantation was demonstrated, but whether these findings are reproducible in nontransplantation populations, such as those with COPD, is still unknown. The aim of this study is to explore the role of BPI in COPD. METHODS: The genotypes of 107 patients with COPD and 110 control subjects were evaluated by polymerase chain reaction and polymorphism analysis of the BPI genes and ELISA analysis of the plasma BPI level. All subjects were men over 40 years old who smoked. RESULTS: BPI mutation PstI (T→C) polymorphism in intron 5 was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62-9.10), and the frequency was significantly increased in the COPD group compared with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In addition, COPD patients exhibited a decreased plasma level of BPI compared with the control group (10.6 ± 2.2 vs 23.4 ± 2.1 ng/ml, p < 0.0001). CONCLUSIONS: BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD. These results demonstrate that BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers.

Using post-bronchodilator FEV1 is better than pre-bronchodilator FEV1 in evaluation of COPD severity.

BACKGROUND: The current standards for the diagnosis and treatment of patients with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria based on post-bronchodilator spirometric values. However, clinical evidence for using the post-bronchodilator FEV1 in the severity classification has not been fully investigated. METHODS: Patients with COPD were enrolled and followed up prospectively between October 2006 and January 2011. We compared the observed 3-year risk of all causes and respiratory mortality with the risk predicted by the pre- and post-bronchodilator percent predicted FEV1. Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance status and severe AECOPD (acute exacerbation) were also compared between the two groups. The different severity classifications of COPD, measured according the GOLD guidelines by post- and pre-bronchodilator percent predicted FEV1 were compared for prediction of mortality. RESULTS: There were 35 deaths among the 300 COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator percent predicted FEV1 was a significant independent predictor of mortality but pre-bronchodilator percent predicted FEV1 was not (p = 0.008 vs 0.126) and it was more strongly correlated with all studied predictors of outcome than the pre-bronchodilator percent predicted FEV1. Kaplan-Meier analysis showed that the discrimination ability to predict mortality from the GOLD criteria using post bronchodilator percent predicted FEV1 (p = 0.009) was better than using pre-bronchodilator percent predicted FEV1 (p = 0.131). CONCLUSIONS: The post-bronchodilator percent predicted FEV1 is better than the pre-bronchodilator percent predicted FEV1 in the evaluation of the severity of disease in COPD patients and is more accurate in predicting the risk of death by the GOLD classification.