Yi-Han Hsiao

The Effect of Cold Temperature on Increased Exacerbation of Chronic Obstructive Pulmonary Disease: A Nationwide Study

Background Seasonal variations in the acute exacerbation of chronic obstructive pulmonary disease (COPD) have been reported. However, the influence of air temperature and other meteorological factors on COPD exacerbation remains unclear. Methods National Health Insurance registry data from January 1, 1999 to December 1, 2009 and meteorological variables from the Taiwan Central Weather Bureau for the same period were analyzed. A case-crossover study design was used to investigate the association between COPD exacerbation and meteorological variables. Results A total of 16,254 cases who suffered from COPD exacerbation were enrolled. We found that a 1°C decrease in air temperature was associated with a 0.8% increase in the exacerbation rate on event-days (95% confidence interval (CI), 1.015–1.138, p = 0.015). With a 5°C decrease in mean temperature, the cold temperature (28-day average temperature) had a long-term effect on the exacerbation of COPD (odds ratio (OR), 1.106, 95% CI 1.063–1.152, p<0.001). In addition, elderly patients and those who did not receive inhaled medication tended to suffer an exacerbation when the mean temperature dropped 5°C. Higher barometric pressure, more hours of sunshine, and lower humidity were associated with an increase in COPD exacerbation. Conclusions This study demonstrated the effect of cold temperatures on the COPD exacerbation rate. Elderly patients and those without inhaled medicine before the exacerbation event were affected significantly by lower mean temperatures. A more comprehensive program to prevent cold stress in COPD patients may lead to a reduction in the exacerbations rate of COPD.

Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea.

STUDY OBJECTIVES To explore the association between the non-apnea sleep disorder (NSD) and autoimmune diseases. DESIGN Cohort study. SETTING Nationwide database research. PARTICIPANTS 84,996 adult patients with NSD diagnoses recorded in the Taiwan National Health Insurance Research Database between 2000 and 2003, after excluding those with antecedent autoimmune diseases. A comparison cohort of 84,996 participants was formed by age-, gender-, income-, and urbanization-matched controls. INTERVENTIONS None. MEASUREMENTS AND RESULTS The two cohorts were followed up for occurrence of autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögrens syndrome (SS), and systemic sclerosis (SSc). A Cox proportional hazards regression model was used for muti-variate adjustment. In patients with NSD, the overall risk for incident autoimmune diseases was significantly higher than in controls (adjusted hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 1.41-1.53). With regard to individual diseases, the risks for SLE, RA, AS and SS among NSD patients were also significantly higher than in controls (HR [95% CI] for SLE, RA, AS, and SS were 1.81 [1.50-2.18], 1.45 [1.36-1.54], 1.53 [1.38-1.70], and 1.51 [1.43-1.60], respectively), whereas the increased risk for SSc did not reach statistical significance (HR: 1.36 [0.82-2.26]). CONCLUSION Patients with non-apnea sleep disorder were associated with a higher risk for developing autoimmune diseases.

Long-acting β2 agonists and corticosteroids restore the reduction of histone deacetylase activity and inhibit H2O2-induced mediator release from alveolar macrophages.

BACKGROUND Treatment of COPD with a combination of long-acting β(2) agonists and corticosteroids is currently used worldwide. The mechanisms of the anti-inflammatory effects and their associations with histone deacetylase (HDAC) activity remain unclear. METHODS Human alveolar macrophages were isolated and stimulated with H(2)O(2) in the presence of varying concentrations of long-acting β(2) agonists and corticosteroids. Supernatants were collected for IL-8 and MMP-9 measurements. Cell lysates were analyzed for HDAC (mainly HDAC1/HDAC2) activity. Quantitative real-time PCR was performed to determine the levels of IL-8 and MMP-9 mRNA. RESULTS Both long-acting β(2) agonists, salmeterol and formoterol, and corticosteroids, fluticasone and budesonide, showed anti-inflammatory effects to a certain extent on H(2)O(2)-induced IL-8 and MMP-9 release in alveolar macrophages. Combinations of long-acting β(2) agonists and corticosteroids exerted greater effects to suppress mediator release, and both transcription and translation of IL-8 and MMP-9 were inhibited. It seemed that the levels of IL-8 and MMP-9 after H(2)O(2) stimulation were inversely associated with the activity of HDAC. H(2)O(2) stimulation resulted in a significant decrease in HDAC activity and was associated with an increase in mediator release. In contrast, treatment with long-acting β(2) agonists, corticosteroids or theophylline restored the H(2)O(2)-induced decrease in HDAC activity and inhibited mediator release. CONCLUSION Combinations of long-acting β(2) agonists and corticosteroids exerted greater effects on the suppression of mediator release in relation to the enhancement of HDAC activity. This supports at least in part the likely contribution of anti-inflammatory effects of long-acting β(2) agonists and corticosteroids to the clinical benefits seen in COPD patients.

Bile acids increase alveolar epithelial permeability via mitogen-activated protein kinase, cytosolic phospholipase A2, cyclooxygenase-2, prostaglandin E2 and junctional proteins

Bile acid (BA) aspiration is associated with various lung diseases. It was hypothesized that BA may induce changes in alveolar epithelium permeability and contribute to the pathogenesis of lung injury.

Hospital Outcomes for Patients with Stage III and IV Lung Cancer Admitted to the Intensive Care Unit for Sepsis-Related Acute Respiratory Failure

BACKGROUND In recent years, intensive care for cancer patients has improved and treatment of critically ill cancer patients has become increasingly aggressive over time. However, not all cancer patients would benefit from aggressive care, especially those with late-stage cancer. OBJECTIVE We aimed to investigate the outcome of late-stage lung cancer patients with sepsis-related respiratory failure and identify predictors of mortality. METHODS From 2007 to 2008, consecutive stage III and IV lung cancer patients admitted to an intensive care unit (ICU) of a teritiary medical center in Taiwan for sepsis-related respiratory failure were retrospectively enrolled. Data at baseline and upon ICU admission were collected. In-hospital survival was analyzed. Variables of the survivors to hospital discharge and patients who died were compared by uni- and multivariate analyses. RESULTS Seventy patients were enrolled. During a mean follow-up period of 30.10 days, 29 (41.4%) patients survived to hospital discharge and 41(58.6%) died. Compared with the survivors, the patients who died had poor performance status, lower serum albumin level, higher percentage of disseminated intravascular coagulation, and more severe organ dysfunction as disclosed by higher Sequential Organ Failure Assessment (SOFA) scores. Multivariate analyses revealed that SOFA score (p=0.026) was the only independent predictor of mortality; 44.8 % (13/29) of survivors were weaned from ventilator during hospitalization. CONCLUSION Among late-stage lung cancer patients with sepsis-related respiratory failure, those with lower SOFA scores seemed to have better survival rate and may benefit from intensive care in the ICU. Early palliative care should be considered for all patients with advanced lung cancer, and hospice care is suggested for those with sepsis-respiratory failure and high SOFA scores.

Budesonide/formoterol maintenance and reliever therapy in asthma control: acute, dose-related effects and real-life effectiveness.

The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real‐life effectiveness are seldom reported.

Post-bronchodilator Reversibility of FEV1 and Eosinophilic Airway Inflammation in COPD

INTRODUCTION The relationship between bronchodilator responsiveness and eosinophilic airway inflammation has not been well documented in COPD. It has been investigated in this retrospective study. This issue has grown in importance due to increasing interest in the asthma-COPD overlap syndrome. METHODS 264 stable COPD patients with no past history of asthma were retrospectively analyzed. Correlation analyses between FEV1 reversibility and sputum eosinophil levels were conducted. Sputum eosinophil levels were dichotomized using FEV1 reversibility cut-off points (>0.4L and >15% vs. >0.2L and >12%) and compared. The effectiveness of FEV1 reversibility to predict sputum eosinophilia (>3%) was analyzed with a logistic regression and a ROC analysis. RESULTS 82 (31.1%) patients with higher FEV1 reversibility values (0.14 vs. 0.11L, P=.01) presented sputum eosinophilia. FEV1 reversibility was weakly correlated with the sputum eosinophil level (r=0.162, P=.008). Patients with FEV1>0.4L and >15% increment had higher sputum eosinophil levels (6.11 vs. 1.02%, P=.049) whereas the level did not differ when dichotomized by FEV1 increment >0.2L and >12%. Very positive FEV1 reversibility (>0.4L and >15%) predicted sputum eosinophilia after adjustment forage, baseline FEV1 and FVC (OR: 4.262, P=.029). In the ROC analysis, the AUC was 0.58 (P=.034), and FEV1 increment>0.4L and >15% had a positive predictive value of 63.6% and an overall accuracy of 70.1%. CONCLUSIONS FEV1 reversibility was weakly correlated with sputum eosinophil levels in COPD. Positive FEV1 reversibility (>0.4L and >15%) is moderately successful in predicting sputum eosinophilia (>3%).

Sleep disorders and an increased risk of Parkinson's disease in individuals with non‐apnea sleep disorders: a population‐based cohort study

Sleep disorders are common non‐motor symptoms in patients with Parkinsons disease. Our study aims to explore the relationship between non‐apnea sleep disorders and future Parkinsons disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non‐apnea sleep disorders without pre‐existing Parkinsons disease were enrolled. An age‐, gender‐, income‐, urbanization‐ and Charlson comorbidity index score‐matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinsons disease, death or until the end of 2010, whichever came first. The Kaplan–Meier analyses revealed patients with non‐apnea sleep disorders tended to develop Parkinsons disease (log‐rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non‐apnea sleep disorders was an independent risk factor for the development of Parkinsons disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54–1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11–1.26, P < 0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59–3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21–1.55, P < 0.001). In conclusion, this study revealed that non‐apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinsons disease.

Adult narcoleptic patients have increased risk of cancer: A nationwide population-based study

BACKGROUND The comorbidity profile, especially cancer risk, of narcoleptic patients has seldom been explored. We used a nationwide database to evaluate the risk of cancer among adult narcoleptic patients. METHODS We conducted the cohort study using National Health Insurance Research Database from 2000 to 2009. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. RESULTS 2833 narcoleptic patients were identified after excluding patients with antecedent malignancy and age younger than 18 years old. The study cohort was observed for 15,913 person-years during a 10-year period. The median follow-up interval was 5.6 ± 3.0 years. Seventy-four cancers occurred in during the follow-up. The risk of all cancers was found significantly increased in adult narcoleptic patients (SIR 1.32; 95% CI, 1.04-1.66, p=0.0248). Regarding sex, the overall cancer risk was increased in female patients (SIR 1.52; 95% CI, 1.05-2.13, p=0.026). Furthermore, females were found to have more head and neck cancers (SIR 6.17; 95% CI, 1.66-15.80, p=0.009) and gastric cancers (SIR 4.87; 95% CI, 1.31-12.48, p=0.02). For males, the incidence of overall and specific cancer types was not significantly increased. CONCLUSIONS Adult narcoleptic patients had a higher risk for cancer. Further research is warranted to elucidate the mechanism underlying its association.

Glycopyrronium bromide inhibits lung inflammation and small airway remodeling induced by subchronic cigarette smoke exposure in mice

The effects of long-acting muscarinic receptor antagonists (LAMAs) have not been evaluated in a model with simultaneous lung inflammation and small airway remodeling induced by cigarette smoke (CS). We exposed the mice to CS for four weeks with daily treatment with a LAMA (glycopyrronium bromide, NVA237) or its vehicle. Human bronchial epithelial cells (PBECs) and lung fibroblasts were exposed to CS extract (CSE) or acetylcholine with or without NVA237 treatment. We found that NVA237, but not its vehicle, suppressed elevations in inflammatory score, epithelial thickness, and peribronchial collagen deposition in CS-exposed mice. NVA237 alleviated CS-induced increased levels of chemokines, inflammatory cells, and total protein in the bronchoalveolar lavage fluid. NVA237 suppressed acetylcholine- or CSE-induced elevations in IL-8 production in PBECs and elevations in proliferation and collagen production in lung fibroblasts. These phenomena were also prevented by a p44/42 MAPK inhibitor. In conclusion, NVA237 exerted a potent suppressive effect on lung inflammation and small airway remodeling induced by subchronic CS exposure.