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.

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.

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.

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.

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

BACKGROUND/PURPOSE: 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 (His(113)/His(113)) 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 His(113) 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.

Eosinophilic pleural effusion as the first presentation of angioimmunoblastic T cell lymphoma.

Eosinophilic pleural effusion (EPE), defined as pleural effusion that contains at least 10% eosinophils among the leukocytes, can be a manifestation of a great variety of diseases. However, eosinophilia is a relatively rare finding in malignant pleural effusions, and it has been used as an indicator of good prognosis. In clinical experience, very few cases of malignant lymphomas accompanied by EPE have been reported. In this report, we present an 82-year-old otherwise healthy man with the initial presentation of left EPE. Pleural biopsy could not yield a definite diagnosis initially. Hookworm ova were also found in the stool and parasite associated with EPE was suspected. However, after anti-parasitic agent treatment with mebendazole, the pleural effusion did not improve. Six months later, bilateral neck, axillary and inguinal lymphadenopathy developed, and lymph node biopsy confirmed the diagnosis of angioimmunoblastic T cell lymphoma, with positive CD10 expression. Therefore, we retrospectively carried out CD10 staining of the sample obtained from pleural biopsy and the positive result confirmed that the etiology of EPE was due to malignant T cell lymphoma. The patient refused chemotherapy and he died 1 month later.

Home exposures, parental atopy, and occurrence of asthma symptoms in adulthood in southern Taiwan.

OBJECTIVE: Parental atopy and environmental exposures at home have been recognized risk factors for adulthood asthma. However, the relative contributions of specific risk factors and the overall contributions of heredity or home exposure remain unexplored. The purpose of this study was to identify predictors and estimate the population attributable risk (PAR) of each exposure for typical asthma symptoms among 26- to 50-year-old Taiwanese. We also investigated whether an interactive effect existed between parental atopy and home exposures on the occurrence of asthma symptoms in adulthood. DESIGN: A cross-sectional study with retrospective components. SETTING: Elementary and middle schools in Southern Taiwan. SUBJECTS: Between March and October 2004, we conducted a cross-sectional survey among schoolchildren's parents from 94 elementary and middle schools in Southern Taiwan. The main outcome measure was typical asthma-like symptoms occurring within the preceding 5 years. Information on hereditary and home exposures was collected by using a self-administered questionnaire. RESULTS: After excluding unqualified questionnaires, data from 24,784 subjects were left for analysis. New-onset asthma was reported for 0.83% of male (n = 80 of 9,662) and 1.36% of female subjects (n = 206 of 15,122). Besides parental atopic factors, environmental tobacco smoke or pet avoidance and visible mold on walls at home were independently associated with the occurrence of asthma symptoms. Mutually adjusted models produced statistically significant associations between any home exposure (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.08 to 3.23; PAR, 28.04%), parental atopy (OR, 4.47; 95% CI, 3.47 to 5.75; PAR, 31.38%), and new-onset asthma. However, there was no interaction between parental atopy and home exposures. CONCLUSIONS: Home exposures and parental atopy both increased the risks of new-onset asthma in adulthood but did not show an interactive effect. These two exposure categories approximately contributed equally to the adulthood asthma.

Indoor and outdoor environmental exposures, parental atopy, and physician-diagnosed asthma in Taiwanese schoolchildren.

OBJECTIVE: Parental atopy and environmental exposures are recognized risk factors for childhood asthma. However, the relative contributions of specific risk factors and the overall contributions of indoor and outdoor exposures remain unexplored. This study was undertaken to identify risk factors, estimate the population attributable risk of each exposure, and compare the data for boys versus girls for physician-diagnosed asthma in Taiwanese schoolchildren. METHODS: During a February to June 2001 cross-sectional national survey, 35 036 6- to 15-year-old schoolchildren were chosen from 22 elementary and 22 middle schools located within 1-km catchment areas of 22 air-monitoring stations in Taiwan. The main outcome measure was physician-diagnosed asthma, as reported by the parents. We investigated hereditary and indoor and outdoor environmental factors for childhood asthma by questionnaire. The adjusted prevalences of questionnaire-determined outdoor indicators were also compared with air-monitoring data. RESULTS: Outdoor air pollutants were associated with parent-reported perceived ambient air pollution. Physician-diagnosed asthma was reported for 8.1% of the boys (1330 of 16 441) and 5.6% of the girls (894 of 16 056). The risk of physician-diagnosed asthma was significantly associated with parental atopy and perceived ambient air pollution in both sexes. The presence of visible cockroaches (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.07-1.59), mold on walls at home (OR: 1.20; 95% CI: 1.01-1.41), and water damage (OR: 1.33; 95% CI: 1.02-1.70) were also associated with asthma in girls; however, only visible mold on walls at home was related to asthma in boys. Mutually adjusted analytical models produced statistically significant associations between any indoor factor and asthma in girls (OR: 1.24; 95% CI: 1.00-1.56) but not in boys (OR: 1.04; 95% CI: 0.87-1.25). For all hereditary and environmental factors, the total population attributable risk was 44.31% in boys and 60.61% in girls. CONCLUSIONS: Parental atopy contributed more to childhood asthma than indoor or outdoor environmental factors. Girls may be more susceptible to indoor factors than boys.

Prediction of arterial blood gas values from venous blood gas values in patients with acute respiratory failure receiving mechanical ventilation.

BACKGROUND AND PURPOSE: Arterial blood gas (ABG) analysis is useful in evaluation of the clinical condition of critically ill patients; however, arterial puncture or insertion of an arterial catheter may cause many complications. This study evaluated whether pH, partial pressure of carbon dioxide (PCO2) and bicarbonate (HCO3-) values of venous blood gas (VBG) could accurately predict their ABG analogs for patients with acute respiratory failure treated by mechanical ventilation in an intensive care unit (ICU). METHODS: Forty six patients who were admitted to the ICU due to acute respiratory failure and treated by mechanical ventilation were included in this study. Blood for VBG analysis was sampled from the cubital or dorsal palmar veins, while ABG was sampled simultaneously from the radial or brachial arteries via an arterial catheter at the other upper extremity. Regression equations and mean percentage-difference equations were derived to predict arterial pH, PCO2, and HCO3- values from their VBG analogs. The equations were validated by evaluating VBG and ABG samples from a separate group of 11 patients. RESULTS: A total of 46 paired samples from 46 patients were evaluated. The mean percentage differences between the venous and arterial values divided by venous values for pH, PCO2, and HCO3- were (mean +/- SD): deltapH (%), 0.50 +/- 0.45; deltaPCO2 (%), 17.09 +/- 9.60; and deltaHCO3- (%), 9.72 +/- 7.73; respectively. Regression equations for prediction of pH, PCO2 and HCO3- values were: arterial pH (pHa) = 0.45 + 0.94 x venous pH (pHv) [r = 0.83, p < 0.0001]; partial pressure of arterial CO2 (PaCO2) = 3.06 + 0.76 x partial pressure of venous CO2 (PvCO2) [r = 0.86, p < 0.0001]; and arterial HCO3- (HCO3-a) = 2.34 + 0.82 x venous HCO3- (HCO3-v) [r = 0.91, p < 0.0001]. The predicted ABG values from the mean percentage-difference equations were derived as follows: pHa = pHv x 1.005; PaCO2 = PvCO2 x 0.83; and HCO3-a = HCO3-v x 0.90. Validation of the regression equations and mean percentage-difference equations revealed only a small (clinically insignificant) variation between the actual and predicted ABG values. CONCLUSIONS: Venous blood gas can accurately predict the ABG values of pH, PCO2 and HCO3- for patients with acute respiratory failure being treated with mechanical ventilation.

Combined intrapleural and intravenous chemotherapy, and pulmonary irradiation, for treatment of patients with lung cancer presenting with malignant pleural effusion. A pilot study.

OBJECTIVES: Patients with non-small-cell lung cancer (NSCLC) and malignant pleural effusion (MPE) are difficult to manage clinically and have a short life expectancy. In this pilot study, we designed a protocol of combined intrapleural (i.p.) and intravenous (i.v.) chemotherapy and pulmonary irradiation to enhance local as well as systemic control of the disease. METHODS: From April 1998 to April 2000, 27 patients with NSCLC and symptomatic MPE were eligible for the study. Patients received pre-radiation chemotherapy (cisplatin 60 mg/m(2) i.p. on day 1; gemcitabine 1,000 mg/m(2) i.v. on days 1, 8, and 15, q4week x 3) after surgical implantation of i.p. and i.v. port-A, followed by radiotherapy (7,020 cGy/39fr), and, finally, post-radiation chemotherapy (docetaxel 60 mg/m(2) q3week x 3-6 i.v.). RESULTS: Grade 1/2 nausea/vomiting and impaired renal function were more common from pre-radiation than post-radiation chemotherapy; however, grade 3/4 toxicities from pre-radiation chemotherapy were minimal. Conversely, grade 3/4 leukopenia and grade 1/2 alopecia, diarrhea, elevation of SGOT/SGPT, and sensory impairment were more common following post-radiation chemotherapy. Only two patients experienced recurrence of pleural effusion. The overall response rate was 55% with 7% complete remission, 48% partial remission, 22% stable disease, and 22% progressive disease. The median failure-free and overall survival was 8 and 16 months, respectively. The one-year survival rate was 63% (95% confidence interval, 45-80%). CONCLUSIONS: We conclude that the combination of i.p. and i.v. chemotherapy and pulmonary irradiation is feasible and should be tested in a larger clinical trial to determine whether survival can be improved for this cohort of patients.

Levels of house dust mite-specific IgE and cockroach-specific IgE and their association with lower pulmonary function in Taiwanese children.

OBJECTIVE: Sensitization to an aeroallergen is known to diminish pulmonary function in young children and adults; however, it remains unclear whether it produces similar effects in adolescents. This study, therefore, examined the relationship between serum allergen-specific IgE levels and pulmonary function in adolescents. DESIGN: Middle-school children were invited for a physician's evaluation and pulmonary function test when not experiencing an asthma attack and for the determination of serum levels of specific IgE to common allergens. SETTING: National Cheng Kung University Hospital, Taiwan. SUBJECTS: Middle-school children in southern Taiwan, who had completed both a nationally administered Chinese version of the International Study of Asthma and Allergies in Childhood questionnaire and a pulmonary function test in October 1996. RESULTS: Forty-two then currently asthmatic children, 38 children with asthma in remission (no reported attack for > 12 months), and 69 children without asthma completed the study. Children with asthma had a significantly lower adjusted forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)) and FEV(1)/FVC than children without asthma. A greater percentage of children with asthma were more sensitized to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and German cockroach but not cat dander or dog dander. Children with asthma with Der f-specific IgE > 100 IU/mL, or cockroach-specific IgE > 0.7 IU/mL showed lower pulmonary function. No such association was found in children without asthma. CONCLUSION: Our findings suggest that sensitization to Der f and German cockroach was a critical factor for the lower pulmonary function observed in middle-school children with asthma.