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Background & aimsWhether living liver donors have a higher risk of biliary tract disease compared with non-donors remains unknown.MethodsData were collected from the Taiwan Longitudinal Health Insurance Database for the 2003-2011 period. The study cohort comprised 1,446 patients aged ≥ 18 years who had served as living liver donors. The primary outcome was the incidence of biliary tract disease. Cox proportional hazards modeling was used to determine the hazard ratios.ResultsThe incidence density rate of biliary tract disease was 13.9-fold higher in the liver donor (LD) cohort than in the non-LD cohort (10.2 vs. 0.71 per 1,000 person-years), with an adjusted hazard ratio (HR) of 14.2 (95% confidence interval [CI] = 7.73-26.1). Stratified by comorbidity, the relative risk of biliary tract disease was higher in the LD cohort than in the non-LD cohort for both patients with or without comorbidity. The incidence density rate of biliary tract disease was significantly higher in the first 3 years (13.5 per 1,000 person-years in the LD cohort). The highest adjusted HR of biliary tract disease for LD patients compared with the non-LD cohort was 22.4 (95% CI = 10.8-46.1) in the follow-up ≤ 3 years.ConclusionLiving liver donors had a higher risk of biliary tract disease compared with non-donors.

[This corrects the article DOI: 10.1371/journal.pone.0128461.].

To clarify the relationship between asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) and depression.We identified 10,911 patients who received an ACOS diagnosis and concurrent treatment between January 2000 and December 2009. Subjects without ACOS were included in the non-ACOS cohort (n = 10,911). Cox proportional hazard regression analysis was performed to compare the risk of depression between the ACOS and non-ACOS cohorts.The risk of depression was higher in the ACOS cohort than in the non-ACOS cohort (adjusted hazard ratios (aHRs) = 1.67, 95% confidence interval [CI] = 1.48-1.88). In the ACOS cohort, the aHRs for depression were [2.44 (95% CI = 1.45-4.11); 2.36 (95% CI = 1.58-3.52)] in patients [aged 20-39 years; without comorbidity]. In the ACOS cohort, the aHRs for depression were 1.70 (95% CI = 1.51-1.93) and 1.84 (95% CI = 1.55-2.19) in patients without inhaled corticosteroids (ICSs) and oral steroids (OSs) use, respectively. Moreover, the aHRs for the risk of depression were 1.16 (95% CI = 0.95-1.41) and 1.12 (95% CI = 0.96-1.29) in patients with ICSs and OSs use, respectively.The risk of depression is higher in ACOS patients, even in those without comorbidities or in young adults. The events of the depression were not significant difference in patients receiving the ICSs/OSs between the ACOS and the non-ACOS cohorts.

Chronic exocrine pancreatic insufficiency can lead to osteoporosis. However, the incidence and risk of osteoporosis after acute inflammation of pancreas remained known. Thus, we conducted a population-based cohort study to clarify the association between acute pancreatitis (AP) and osteoporosis.Patients newly diagnosed with AP with index date between 2000 and 2011 were identified from the National Health Insurance Research Database. Osteoporosis were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied age-, sex-, and comorbidities-adjusted variable Cox proportional hazard models for assessing the association between AP and osteoporosis. Moreover, these models were used to adjust for the influences of patient characteristics and comorbidities.In this study, 4,016 patients were included in the AP cohort (males, 67.9%; mean age, 51.8 years) and 4,016 matched controls in the non-AP cohort. After a mean follow-up period of 4.97 and 5.21 years in the AP and non-AP cohorts, respectively, the incidence of osteoporosis was 8.22 per 1000 person-years in the AP cohort. The AP cohort had a higher risk [adjusted hazard ratio (aHR) = 1.27, 95% confidence interval (CI) = 1.02-1.58] of osteoporosis than did the non-AP cohort. The risk of osteoporosis was highest in the female patients of the AP cohort (aHR = 2.26, 95% CI = 1.85-2.76) and patients aged 50-64 years (aHR = 4.14, 95% CI = 3.13-5.47).AP patients are at a risk of osteoporosis, especially female gender and age 50-64 years. Those with > 3 episodes of AP had highest significant risk of developing osteoporosis.

Hepatitis C virus (HCV) infection is associated with increased systemic oxidative stress, which leads to cardiovascular events, diabetes, and chronic kidney disease. Similarly, cataract is also associated with increased oxidative stress. The association between HCV infection and increased risk of cataract remains unclear.A total of 11,652 HCV-infected patients and 46,608 age- and sex-matched non-HCV infected patients were identified during 2003-2011. All patient data were tracked until a diagnosis of cataract, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated.The mean follow-up durations were 5.29 and 5.86 years for the HCV and non-HCV cohorts, respectively. The overall incidence density rate for cataract was 1.36 times higher in the HCV cohort than in the non-HCV cohort (1.86 and 1.37 per 100 person-y, respectively). After adjusting for age, sex, comorbidities of diabetes, hypertension, hyperlipidemia, asthma, chronic obstructive pulmonary disease, coronary artery disease, and anxiety, patients with HCV infection had an increased risk of cataract compared with those without HCV infection [adjusted HR = 1.23, 95% confidence interval (CI) = 1.14-1.32]. HCV-infected patients receiving interferon-ribavirin therapy had a 1.83 times higher (95% CI = 1.40-2.38) risk of cataract than non-HCV infected patients did.HCV infection, even without the complication of cirrhosis, is associated with an increased risk of cataract, and this risk is higher in HCV-infected patients undergoing interferon-ribavirin therapy.

The relationship between respiratory tuberculosis (RT) and incident fragility fracture and osteoporosis/fragility fracture in the general population is not well determined; therefore, we conducted a nationwide cohort study to investigate this relationship.We used the National Health Insurance Research Database of Taiwan to identify 6612 newly diagnosed patients with RT (RT cohort) and 13220 patients without RT (non-RT cohort) from 1999 to 2005. The mean durations of follow-up were (6.73 ± 4.00 years, 8.11 ± 3.24 years) in the (RT cohort, non- RT cohort); respectively. The occurrence of incident fragility fracture and osteoporosis/fragility fracture were followed up until the end of 2011. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) and 98% CIs of incident fragility fracture and osteoporosis/fragility fracture were estimated using the multivariable Cox proportional hazard model after adjusting for age, sex, occupation, drug use, and comorbidities.A Cox proportional hazards regression analysis was performed and showed the aHRs of [incident fragility fracture; osteoporosis/fragility fracture] were [1.69 (95% CI = 1.26-2.28, 98% CI = 1.18-2.44); 1.42 (95% CI = 1.25-1.61, 98% CI = 1.21-1.65)] between the RT and non-RT cohorts. Regarding the sex, the aHRs of the [incident fragility fracture; osteoporosis / fragility fracture] were [1.57 (98% CI = 1.10-2.23, 98% CI = 1.02-2.41); 1.15 (95% CI = 0.97-1.36, 98% CI = 0.94-1.41)] in the men. The aHRs of the RT cohort without oral steroid use in the [incident fragility fracture; osteoporosis / fragility fracture] were [1.87 (95% CI = 1.20-2.90, 98% CI = 1.09-3.19); 1.41 (95% CI = 1.19-1.67, 98% CI = 1.14-1.74)].The RT associated with the incident fragility fracture, either in men or absence of oral steroid use.

PURPOSE:We conducted a nationwide cohort study to investigate the relationship between systemic lupus erythematosus (SLE) and the risk of incident respiratory failure. METHODS:From the National Health Insurance Research Database, we identified 11 533 patients newly diagnosed with SLE and 46 132 controls without SLE who were randomly selected through frequency-matching according to age, sex, and index year. Both cohorts were followed until the end of 2011 to measure the incidence of incident respiratory failure, which was compared between the 2 cohorts through a Cox proportional hazards regression analysis. RESULTS:The adjusted hazard ratio (aHR) of incident respiratory failure was 5.80 (95% confidence interval [CI] = 5.15-6.52) for the SLE cohort after we adjusted for sex, age, and comorbidities. Both men (aHR = 3.44, 95% CI = 2.67-4.43) and women (aHR = 6.79, 95% CI = 5.93-7.77) had a significantly higher rate of incident respiratory failure in the SLE cohort than in the non-SLE cohort. Both men and women aged 24 outpatient visits and hospitalizations per year had a higher incident respiratory failure risk (aHR = 21.7, 95% CI = 18.0-26.1) compared with the non-SLE cohort. CONCLUSION:Patients with SLE are associated with an increased risk of incident respiratory failure, regardless of their age, sex, and pre-existing comorbidities; especially medical services with higher frequency.

BACKGROUND:There is a demonstrated association between asthma and irritable bowel syndrome (IBS). In this study, we examined the bidirectional association between asthma and IBS using a nationwide database. METHODS:We conducted two retrospective cohort studies using data obtained from the National Health Insurance of Taiwan. Study 1 included 29,648 asthma patients newly diagnosed between 2000 and 2010. Study 2 included 29,875 IBS patient newly diagnosed between 2000 and 2010. For each study, four subjects without asthma and IBS were selected, respectively, frequency-matched by sex, age, and the diagnosis date. All four cohorts were followed up until the end of 2011 to estimate incident IBS for Study 1 and incident asthma for study 2. Adjusted hazard ratios (aHRs) were estimated using the Cox proportional hazards model after controlling for sex, age and comorbidities. RESULTS:The incidence of IBS was 1.89 times higher in the asthma cohort than in the comparison cohort (8.26 vs. 4.36 per 1,000 person-years), with an aHR of 1.57 [95% confidence interval (CI) = 1.47-1.68]. The aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. In contrast, the incidence of asthma was 1.76 times higher in the IBS cohort than the comparison cohort (7.09 vs. 4.03 per 1,000 person-years), with an aHR of 1.54 (95% CI = 1.44-1.64). Similarly, aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. CONCLUSION:The present study suggests a bidirectional association between asthma and IBS. Atopy could be a shared pathophysiology underlying this association, deserving a further investigation.

The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34-1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33-1.90), those aged 50-64 years (1.66; 95% CI, 1.31-2.09), or those without comorbidities (1.82; 95% CI, 1.54-2.13).Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.

BACKGROUND:There are several publications reported that obstructive sleep apnea (OSA) was associated with asthma. However, large-scaled, population-based cohort study has been limited. We aimed to examine the risk of OSA among adult patients with asthma in an Asian population. METHODS:We conducted a retrospective cohort study using data from the National Health Insurance (NHI) of Taiwan. The asthma cohort included 38,840 newly diagnosed patients between 2000 and 2010. The date of diagnosis was defined as the index date. Each patient was randomly matched with four people without asthma according to gender, age, and the index year as the comparison cohort. The occurrence of OSA was followed up until the end of 2011. The risk of OSA was estimated using the Cox proportional hazard model after adjusting for gender, age, and comorbidities. RESULTS:The overall incidence of OSA was 2.51-fold greater in the asthma cohort than in the comparison cohort (12.1 versus 4.84 per 1000 person-years). Compared to non-asthma subjects, the adjusted hazard ratio (aHR) of OSA increased to 1.78 for asthma patients with one or less annual emergency room (ER) visit, and 23.8 for those who visited ER more than once per year. In addition, aHR in patients with inhaled steroid treatment compared to those without steroid treatment was 1.33 (95% CI = 1.01-1.76). CONCLUSION:Patients with asthma have a significantly higher risk of developing OSA than the general population. The results suggest that the risk of OSA is proportional to asthma control and patients with inhaled steroid treatment have a higher risk for OSA than those without steroid treatment.

The role of advanced bronchoscopic diagnostic techniques in the detection and staging of lung cancer has increased sharply in recent years. The development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions (PLLs). We investigated the impact of using EBUS as a diagnostic method for tissue acquisition in lung cancer patients.In a single center observational retrospective study, 3712 subjects were diagnosed with lung cancer from 2003 to 2013 (EBUS was introduced in 2008). Thus, we divided the data into two periods: the conventional bronchoscopy period (2003 to 2007) and the EBUS period (2008 to 2013).A total of 3712 patients were included in the analysis. Comparing the conventional bronchoscopy period with the EBUS period data, there has been a significant reduction in the use of diagnostic modalities: CT-guided biopsy (P < 0.0001) and pleural effusion cytology (P < 0.0001). The proportion of subjects diagnosed using bronchoscopy significantly increased from 39.4% in the conventional period to 47.4% in the EBUS period (P < 0.0001). In the EBUS period, there has also been a significant increase in the proportion of patients proceeding directly to diagnostic surgery (P < 0.0001). Compared to bronchoscopy, the incidence of complications was higher in those who underwent CT guide biopsy. The incidence of iatrogenic pneumothorax significantly decreased in the EBUS period.Advanced bronchoscopic techniques are widely used in the diagnosis of lung cancer. At our institution, the increasing use of EBUS for providing lung cancer diagnosis has led to a significant reduction in other diagnostic modalities, namely CT-guided biopsy and pleural effusion cytology. These changes in practice also led to a reduction in the incidence of complications.

BACKGROUND: Previous studies have suggested that chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. There are some evidence that people with diabetes are at a risk of developing many forms of cancer, but inconclusive with regard to lung cancer. The aim of this study was to evaluate whether COPD with or without type 2 diabetes mellitus (T2DM) influences the risk of developing lung cancer. METHODS: This is a retrospective cohort study consisting of 20,730 subjects newly diagnosed with COPD ("cases"). Their data was collected from the National Health Insurance system of Taiwan from 1998 to 2010. Among these patients, 5,820 patients had T2DM and 14,910 patients did not have T2DM. The retrospective matched control group consisted of 20,729 subjects without either COPD or T2DM. The control group was matched with the cases for sex, age, and index year (the year that the patient was diagnosed with COPD). The subjects were followed until the end of 2011. RESULTS: The findings of our study showed that the risk of lung cancer was higher in the COPD group than in the non-COPD group, with adjusted hazard ratio (HR) of 5.02 [95% confidence interval (CI) = 4.23-5.94] among total case group, adjusted HR was 5.38 (95% CI = 4.52-6.40) in the cohort without T2DM and adjusted HR was 4.05 (95% CI = 3.26-5.03) in the cohort with T2DM. We observed a significantly protective effect from lung cancer (adjusted HR = 0.75, 95% CI = 0.63-0.90) of diabetic cohort than non-diabetic cohort among patients with COPD. CONCLUSION: Patients with COPD had a significantly higher risk of developing lung cancer than healthy people. However, there was a protective effect of T2DM for lung cancer among patients with COPD. Further investigation may be needed to corroborate the mechanism or bring up reliable reasons.

BACKGROUND: There is increasing evidence that autoimmune disease is associated with development of chronic obstructive pulmonary disease (COPD). We aim to assess the relationship between systemic lupus erythematosus (SLE) and COPD risk in a nationwide population. METHODS: We conducted a retrospective cohort study using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD). We identified 10,623 patients with SLE newly diagnosed between 2000 and 2010. Each patient was randomly frequency-matched with four people without SLE on age, sex, and index year from the general population. Both cohorts were followed up until the end of 2010 to measure the incidence of COPD. The risk of COPD was analyzed using Cox proportional hazards regression models including age, sex, index year and comorbidities. RESULTS: The overall incidence rate of COPD was 1.73-fold higher in the SLE cohort than in the control cohort (17.4 vs. 10.1 per 10,000 person-years, 95% CI = 1.62-1.84). Age related analysis showed increased incidence of COPD with age in both SLE and control cohorts. However, adjusted HR maximum was observed in the youngest age group (adjusted HR: 4.33, 95% CI, 2.39-7.85) while adjusted HR minimum was witnessed in the oldest age group (adjusted HR: 1.19, 95% CI, 0.85-1.22). CONCLUSION: Patients with SLE have a significant risk of developing COPD than the control population. Based on the findings from this study, it can be hypothesized that in addition to cigarette smoke SLE may be a determining factor for COPD incidence. However, further investigation is needed to corroborate this hypothesis.

An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P