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

Background/PurposeLittle 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.MethodsA 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.ResultsTwenty-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).ConclusionAfter 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

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

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

Chronic and Repeated Chlamydophila pneumoniae Lung Infection can Result in Increasing IL-4 Gene Expression and Thickness of Airway Subepithelial Basement Membrane in Mice

Chlamydophila pneumoniae infection has been associated with several pulmonary and cardiac diseases. However, it has not been explored for its ability to activate the same immunopathologic mechanisms of asthma, namely, a predominant Th2 immune response and structural changes that are termed airway remodeling. This study evaluated immune responses in the lung and airway pathology of BALB/c mice with chronic and repeated C. pneumoniae infections. Methods: Mice were inoculated intranasally with 5 × 106 inclusion-forming units of C. pneumoniae TWAR strain, and re-inoculated at 14 and 42 days after the primary inoculation. Cytokine gene expression in bronchoalveolar lavage (BAL) cells was analyzed by RT-PCR on day 70. Airway pathology was also evaluated by morphometric measurements. Results: A significant increase of interleukin (IL)-4 mRNA was detected in BAL cells in infected mice, and a significant increase in subepithelial basement membrane thickness of the airways was also noted in infected mice as compared with control mice (8.95 ± 0.28 μm vs. 5.54 ± 0.22 μm, p < 0.0001). We further analyzed the correlation between IL-4 cytokine expression and the increased subepithelial basement membrane thickness of airways in infected mice. We found that mice with increased IL-4 mRNA expression had significant increases in the thickness of subepithelial basement membrane as compared with mice without increased IL-4 mRNA expression (9.87 ± 0.51 μm vs. 6.49 ± 0.52 μm, p < 0.0001). Conclusion: It is believed that our results demonstrated for the first time that chronic and repeated infections with C. pneumoniae increased IL-4 gene expression and thickness of airway subepithelial basement membrane in mice

Repeated Pneumonia Severity Index Measurement After Admission Increases its Predictive Value for Mortality in Severe Community-acquired Pneumonia

Severe community-acquired pneumonia (CAP) is associated with high hospital mortality, and accurate assessment of patients is important for supporting clinical decision making. The Pneumonia Severity Index (PSI) is a good tool for predicting disease severity, especially in the low-risk group of patients with CAP. We investigated whether the change in PSI measurement after admission could identify patients at high risk of mortality from CAP. Methods: We prospectively studied 250 inpatients with CAP. PSI was measured at admission and 72 hours later at a tertiary referral medical center from May 2005 to February 2006. The initial and repeated PSI results were compared. Hospital mortality was used as the outcome measure. Results: Initial PSI in high-risk patients (PSI class > IV) had a low specificity (37%), and a low positive predictive value (PPV) (17%). Increased repeated PSI score, as compared with initial score, was associated with an increased mortality rate (from 7.8% to 33.3% in class IV, and 25.3% to 53.3% in class V; p < 0.0001), and improved the predictive value, with 94% specificity and a PPV of 46% for mortality in high-risk patients. Conclusion: Increased PSI score, 72 hours after admission, for patients with CAP improved the predictive value of PSI score and more accurately identified patients with a high risk of mortality

Clinical Features of Fatal Asthma

To characterize the clinical features of fatal asthma, we retrospectively analyzed the clinical characteristics of patients who died of an acute asthma attack in our hospital during a 15-year period from 1989 to 2003. Twelve patients had fatal asthma during this period, including eight who were dead on arrival in the emergency room (ER) and three who died within 1 hour of admission to the ER. Patients were categorized into three groups according to the clinical presentations during the fatal attack: (1) rapid (< 3 hours) decompensation in four patients; (2) gradual development of respiratory failure over several days in two patients; and (3) acute deterioration after unstable asthma lasting several days in six patients. All patients in groups 1 and 2 had reported previous near-fatal attacks. The proportion of young patients was highest in group 3, with half of them (3/6) younger than 35 years of age. Only one patient in group 3 had had a previous near-fatal attack. Five of the seven patients, with previous near-fatal attacks, had a pattern of decompensation during their fatal attack that was similar to their previous attacks. In conclusion, nearly all patients with fatal asthma in this study died outside of the hospital or within 1 hour after admission to the ER. Patients had patterns of decompensation during the fatal attack that were similar to those of their previous attacks. Early detection of warning signs, early admission to the ER, adequate treatment, and extremely close observation of patients, especially within 1 hour after ER arrival, may prevent or decrease the incidence of fatal asthmatic attack

Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response

Microsomal epoxide hydrolase (EPHX) is an important enzyme that metabolizes harmful reactive epoxides from smoking. Genetic variations of this enzyme are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD). The aim of this study was to confirm and advance our knowledge of the role of this genetic variation in COPD. In addition, the association between this gene and important COPD-related phenotype bronchodilator responses (BDRs) was studied. Methods: This was a hospital-based case–control study. The EPHX1 genetic mutations of 105 smokers with COPD and 103 control smokers without COPD were evaluated by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The association of genetic mutations and COPD phenotypes was also studied. Results: Subjects with EPHX1 113 (His113/His113) homozygote mutation had a strong correlation with COPD (odds ratio: 2.7, 95% confidence interval: 1.5–5.2). In addition, compared with other genotypes, the His113 homozygote mutation patients had significantly lower BDRs, as shown by the absolute and percentage changes from baseline, in COPD patients (91.7 ± 12.5 mL vs. 141.6 ± 15.1 mL, p = 0.01 and 8.3 ± 1.2% vs. 13.4 ± 1.4%, p = 0.006). Conclusion: A strong correlation between the EPHX1 113 mutant homozygote and smoking-related COPD was noted. This genetic polymorphism was also associated with lower BDRs in COPD patients

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

: 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

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

Abstract 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

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