Ming Chia Lee

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

Objective Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. Design, Setting, and Participants This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. Main Outcome Measures Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. Results The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768–2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. Conclusions Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients.

Hepatotoxicity due to first-line anti-tuberculosis drugs: A five-year experience in a Taiwan medical centre

BACKGROUND Hepatotoxicity with first-line drugs, a major complication of anti-tuberculosis treatment, has not been studied by time-dependent analysis. DESIGN Adult patients diagnosed with pulmonary tuberculosis (PTB) from 2005 to 2009 were reviewed retrospectively. Hepatotoxicity during anti-tuberculosis treatment was defined by symptomatic elevation of liver transaminases ≥3 times the upper limit of normal, or ≥5 times if asymptomatic. Risk factors for hepatotoxicity were investigated using time-dependent Cox regression analysis. RESULTS Of 926 patients identified and followed for 4122.9 person-months (pm), 111 (12.0%) developed hepatotoxicity after a median 38.0 days from start of treatment. Around 3.5% had severe hepatotoxicity. The most common symptoms were general malaise and poor appetite. The incidence rate of hepatotoxicity was 0.59, 0.69 and 3.71/100 pm for isoniazid, rifampicin (RMP) and pyrazinamide (PZA), respectively. Old age, female sex, autoimmune disease, human immunodeficiency virus infection, more days with PZA in the last 8-14 days, and fewer days with RMP in the last 15-21 days before hepatotoxicity were independent risk factors for hepatotoxicity during treatment. CONCLUSION A significant number of adult patients on first-line treatment experience hepatotoxicity. PZA is the most common causative drug. For high-risk patients, careful adjustment of the anti-tuberculosis regimen and regular monitoring of liver transaminases are necessary.

Risk factors for pulmonary tuberculosis in patients with chronic obstructive airway disease in Taiwan: a nationwide cohort study.

BackgroundAn association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use. Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.MethodsWe selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.ResultsAmong 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected. Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205–2.762]) were independent risk factors for TB. Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists. Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB. The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.ConclusionKeeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications. Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice.

Optimal Duration of Anti-TB Treatment in Patients With Diabetes: Nine or Six Months?

BACKGROUND Diabetes mellitus (DM) increases the risk of TB recurrence. This study investigated whether 9-month anti-TB treatment is associated with a lower risk of TB recurrence within 2 years after complete treatment than 6-month treatment in patients with DM with an emphasis on the impact of directly observed therapy, short course (DOTs). METHODS Patients with pulmonary but not extrapulmonary TB receiving treatment of 173 to 277 days between 2002 and 2010 were identified from the National Health Insurance Research Database of Taiwan. Patients with DM were then selected and classified into two groups based on anti-TB treatment duration (9 months vs 6 months). Factors predicting 2-year TB recurrence were explored using Cox regression analysis. RESULTS Among 12,688 patients with DM and 43,195 patients without DM, the 2-year TB recurrence rate was 2.20% and 1.38%, respectively (P < .001). Of the patients with DM, recurrence rate decreased from 3.54% to 1.19% after implementation of DOTs (P < .001). A total of 4,506 (35.5%) were classified into 9-month anti-TB treatment group. Although a 9-month anti-TB treatment was associated with a lower recurrence rate (hazard ratio, 0.76 [95% CI, 0.59-0.97]), the benefit disappeared (hazard ratio, 0.69 [95% CI, 0.43-1.11]) under DOTs. Other predictors of recurrence included older age, male sex, malignancy, earlier TB diagnosis year, culture positivity after 2 months of anti-TB treatment, and anti-TB treatment being ≤ 80% consistent with standard regimen. CONCLUSIONS The 2-year TB recurrence rate is higher in a diabetic population in Taiwan and can be reduced by treatment supervision. Extending the anti-TB treatment by 3 months may also decrease the recurrence rate when treatment is not supervised.

Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan

Background:Obstructive uropathy and chronic urinary tract infection increase the risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic urinary tract inflammation, lead to obstructive uropathy, and potentially contribute to the development of urinary tract cancer. However, the association between UTB and urinary tract cancer has not been studied.Methods:This study enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health insurance research database in Taiwan and investigated the risk factors for urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary tract cancer in the general population without TB was also calculated for comparison.Results:The TB patients had a mean age of 57.5±19.5 years. Of the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%) developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis revealed that age, male sex, end-stage renal disease, obstructive uropathy, arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01–5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio of UTB was higher among female patients (5.26 (2.12–13.06)) than that among male patients (2.96 (1.57–5.60)).Conclusion:Urinary tuberculosis had a strong association with urothelial carcinoma, but not with renal cell carcinoma. In TB endemic areas, the urinary tract of TB patients should be scrutinised. It is also imperative that these patients be followed-up carefully in the post-treatment period, and urinalysis, ultrasonography or endoscopy should be an integral part of the follow-up.

Inhaled corticosteroids increase the risk of pneumonia in patients with chronic obstructive pulmonary disease: A nationwide cohort study

Abstract The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial. From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort). Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables. Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort). The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test. A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively. In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02–1.11] for per 80 mg of budesonide). Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline. In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001). This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE. ICS should be judiciously used in indicated COPD patients.

Fluoroquinolone use delays tuberculosis treatment despite immediate mycobacteriology study

Despite its excellent activity against Mycobacterium tuberculosis [1], empirical fluoroquinolone (FQ) therapy has been associated with delayed initiation of appropriate treatment [2–4] and acquired resistance [5, 6] in tuberculosis (TB) patients presenting as community-acquired pneumonia (CAP). A previous study conducted in intensive care unit revealed immediate mycobacteriology study may possibly prevent the delay in anti-TB treatment [7]. However, this hypothesis has not been confirmed. Empirical fluoroquinolone use for ≥7 days delays antituberculosis treatment despite immediate mycobacteriology study http://ow.ly/L8fIm

The impact of diabetes mellitus and its control on the development of tuberculosis: A nationwide longitudinal study in Taiwan

Diabetic mellitus (DM) is a well‐known risk factor of tuberculosis (TB). However, there is paucity of reports on the impact of diabetic control and adherence to anti‐diabetic treatment on the risk of TB. This nationwide cohort study aimed to address these issues.

Mycobacterium tuberculosis nucleic acid amplification tests reduce nosocomial tuberculosis exposure in intensive care units: A nationwide cohort study.

This retrospective national surveillance study investigated the burden of and risk factors for nosocomial exposure of pulmonary tuberculosis (TB) in intensive care units.

Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: A cohort study in Taiwan

Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Both erlotinib and gefitinib, the two first‐generation EGFR‐TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue. This retrospective nationwide cohort study enrolled NSCLC patients who received EGFR‐TKIs after previous chemotherapy in Taiwan between 1996 and 2010 from the National Health Insurance Research Database. Clinical response and survival after receiving erlotinib and gefitinib were compared using logistic and Cox regression analyses, respectively. Inverse propensity score weighting and a sensitivity analysis in the EGFR‐TKI responder (clinical improvement by taking EGFR‐TKIs for 90 days), adherent patients (receiving EGFR‐TKI on a daily basis), adenocarcinoma, and adenocarcinoma with second‐line TKIs subgroup were performed for bias adjustment. A total of 7222 patients, including 4592 (63.6%) who received gefitinib, were identified. In the survival analysis, erlotinib was associated with a decline in 1‐year progression‐free survival (PFS) (hazard ratio, HR: 1.15 [1.09–1.21]) and overall survival (OS) (HR: 1.10 [1.03–1.18]). The effects of various TKIs were consistent in the 4939 EGFR‐TKI responders, adherent subgroup, adenocarcinoma subgroup, and adenocarcinoma with second‐line TKIs subgroup. In previously treated EGFT‐TKI‐naive NSCLC patients, those receiving gefitinib exhibited a longer PFS and OS than those receiving erlotinib. Additional large‐scale randomized controlled trials are warranted to confirm this finding.