Chin-Chung Shu

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.

Use of high-dose inhaled corticosteroids is associated with pulmonary tuberculosis in patients with chronic obstructive pulmonary disease.

The use of high-dose inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) has recently been shown to increase the incidence of pneumonia. However, to our knowledge, the impact of high-dose ICS on pulmonary tuberculosis (TB) has never been investigated. To study that impact, we conducted a retrospective study including patients aged more than 40 years old with irreversible airflow limitation between August 2000 and July 2008 in a medical center in Taiwan. Of the 36,684 patients who underwent pulmonary function testing, we included 554 patients. Among them, patients using high-dose ICS (equivalent to >500 &mgr;g/d of fluticasone) were more likely to have more severe COPD and receive oral corticosteroids than those using medium-dose, low-dose, or no ICS. Sixteen (3%) patients developed active pulmonary TB within a follow-up of 25,544 person-months. Multivariate Cox regression analysis revealed that the use of high-dose ICS, the use of 10 mg or more of prednisolone per day, and prior pulmonary TB were independent risk factors for the development of active pulmonary TB. Chest radiography and sputum smear/culture for Mycobacterium tuberculosis should be performed before initiating high-dose ICS and regularly thereafter. Abbreviations: COPD = chronic obstructive pulmonary disease, FEV1 = forced expiratory volume in the first second, FVC = forced vital capacity, HD = high dose, ICS = inhaled corticosteroids, LD = low dose, MD = medium dose, TB = tuberculosis.

Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study.

Background:  Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer.

Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy

OBJECTIVE Conventional methods for diagnosing tuberculous pleurisy (TB pleurisy) are either invasive or have a long turn-around-time. Performances of pleural adenosine deaminase (ADA), ADA2, interferon-gamma (IFN-γ), and interferon-gamma release assays (IGRA) as diagnostic tools for TB pleurisy were evaluated. METHODS Eighty-eight patients with lymphocyte-predominant pleural exudates between June 2010 and March 2011, including 31 with clinically diagnosed TB pleurisy, were prospectively studied. Pleural ADA and ADA2 activity were measured by colorimetric method, IFN-γ levels by enzyme-linked immuno-sorbent assay, and IGRA by enzyme-linked immuno-spot (T-SPOT.TB) assay. RESULTS Pleural ADA, ADA2, and IFN-γ levels, but not the proportion of positive T-SPOT.TB assay, were significantly higher in patients with TB pleurisy than in those without TB pleurisy. The area under the receiver-operating-characteristic (ROC) curve was 0.920, 0.893, 0.875, and 0.544 for IFN-γ, ADA2, ADA, and T-SPOT.TB assay, respectively. The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100%. CONCLUSIONS Pleural ADA, ADA2 and IFN-γ, but not T-SPOT.TB assay, are all sensitive and specific for TB pleurisy. In patients with lymphocyte-predominant pleural exudates, ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL in pleural effusion imply a very high probability of TB pleurisy.

Clinical significance of isolation of nontuberculous mycobacteria in pulmonary tuberculosis patients.

BACKGROUND Clinical significance of isolation of nontuberculous mycobacteria (NTM) from respiratory specimens in patients with pulmonary tuberculosis is unknown. This study aimed to investigate the prevalence and clinical impact of NTM in pulmonary tuberculosis patients. METHODS We retrospectively reviewed data of patients with culture-confirmed pulmonary tuberculosis from 2000 to 2006. Those in whom NTM were isolated from respiratory specimens collected within two months before and nine months after the index culture of tuberculosis was plated were compared with those without NTM. Patients were followed for one year after initiation of anti-tuberculous treatment. RESULTS Among 2133 patients with pulmonary tuberculosis, 48 (2.3%) with multiple and 106 (5.0%) with one isolate(s) of NTM were identified. Another 144 without NTM were selected and compared. The one-year mortality rates were similar among three groups. Patients with multiple NTM isolates were more likely to be symptomatic, sought medical help earlier, had smear-positive respiratory specimens, and received anti-tuberculous treatment later than those with single/no isolate(s). Cavities were more commonly visualized radiographically in patients with multiple/single NTM isolate(s) than those without NTM isolates. The mean duration of anti-tuberculous treatment was 8.8 months for patients with multiple NTM isolates, significantly longer than that in patients with single (7.6 months) and no NTM isolate(s) (7.5 months). CONCLUSIONS NTM were present in the respiratory tract of 7.3% of patients with pulmonary tuberculosis. Although the outcomes were similar, the presence of NTM was associated with different clinical manifestations and had a significant impact on the treatment of tuberculosis.

Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis.

Background Tuberculosis is a common infectious disease in long-term dialysis patients. The prevalence of latent tuberculosis infection (LTBI) in this population is unclear, particularly in those receiving peritoneal dialysis (PD). This study investigated the prevalence of LTBI in patients receiving either hemodialysis (HD) or PD to determine predictors of LTBI and indeterminate results of interferon-gamma release assay. Methods Patients receiving long-term (≥3 months) HD or PD from March 2011 to February 2012 in two medical centers were prospectively enrolled. QuantiFERON-Gold in tube (QFT) test was used to determine the status of LTBI after excluding active tuberculosis. The LTBI prevalence was determined in patients receiving different dialysis modes to obtain predictors of LTBI and QFT-indeterminate results. Results Of 427 patients enrolled (124 PD and 303 HD), 91 (21.3%) were QFT-positive, 316 (74.0%) QFT-negative, and 20 (4.7%) QFT-indeterminate. The prevalence of LTBI was similar in the PD and HD groups. Independent predictors of LTBI were old age (OR: 1.034 [1.013–1.056] per year increment), TB history (OR: 6.467 [1.985–21.066]), and current smoker (OR: 2.675 [1.061–6.747]). Factors associated with indeterminate QFT results were HD (OR: 10.535 [1.336–83.093]), dialysis duration (OR: 1.113 [1.015–1.221] per year increment), anemia (OR: 8.760 [1.014–75.651]), and serum albumin level (OR: 0.244 [0.086–0.693] per 1 g/dL increment). Conclusion More than one-fifth of dialysis patients have LTBI. The LTBI prevalence is similar in PD and HD patients but is higher in the elderly, current smokers, and those with prior TB history. Such patients require closer follow-up. Repeated or alternative test may be required for malnutrition patients who received long length of HD.

Evaluating the performance of a hospitalist system in Taiwan: a pioneer study for nationwide health insurance in Asia.

BACKGROUND The national health insurance (NHI) in Taiwan covers almost the entire population and controls medical costs. However, there is increasing patient admission and shortage of inpatient care staff. The hospitalist system may be a solution. OBJECTIVE To study the efficiency of the hospitalist system under the NHI in Taiwan. DESIGN Prospective observational study. METHODS Under the NHI, a hospitalist-run ward (HW) was set-up in a medical referral center for patients admitted from the emergency department. The cohort was observed and compared to the internist-run wards (IWs) in terms of performance. RESULTS From November 2009 to January 2010, 377 patients admitted to the HW and 433 to the IWs were enrolled. Patients in the HW were older and had poorer functional status and more underlying comorbidities. The HW group also had lower admission costs and shorter lengths of hospital stay (LOS) than the IW group. Due to different demographics, propensity analysis was performed on 101 matched pairs of patients, which showed significantly lower cost and shorter LOS in HW patients despite similar mortality and readmission rates. CONCLUSIONS The hospitalist system has higher efficiency than the internist-run general wards under the NHI system in terms of costs and length of hospitalization. It may serve as an alternative model to address rising admissions and staff shortages.