The diagnosis of pulmonary tuberculosis: a Korean perspective

Despite global efforts to eliminate tuberculosis, the disease remains of huge global public health problem. Prompt and accurate diagnosis of pulmonary tuberculosis is essential to ensure appropriate therapy. Chest radiography, sputum smear microscopy, mycobacterial culture, and nucleic acid amplification test are essential diagnostic elements, and appropriate use of recently introduced molecular tests and chest computed tomography could improve the accuracy of early diagnosis

Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer

SummaryBackgroundChronic inflammation has been implicated in the pathogenesis of several cancers, including lung and laryngeal cancer. The objective of the study is to elucidate the association between ICS use and diagnosis of lung and laryngeal cancer.MethodsA nested case–control study based on the Korean national claims database included new adult users of inhaled medications between January 1, 2007, and December 31, 2010. Patients diagnosed with lung cancer or laryngeal cancer after enrollment were identified as cases and up to five control individuals matched for age, sex, diagnosis of asthma or COPD, Charlson Comorbidity Index scores, number of health care visits, and initiation date were selected.ResultsFrom the 792,687 eligible cohort, 9177 individuals diagnosed with lung cancer were matched with 37,048 controls. Additionally, 408 laryngeal cancer patients and 1651 controls were matched. ICS use was associated with a decreased rate of lung cancer diagnosis [adjusted odds ratio (aOR), 0.79; 95% confidence interval (CI), 0.69–0.90]. The inverse association between ICS use and lung cancer risk was dose dependent (P < 0.0001 for the trend). However, no reduction in the risk of laryngeal cancer among ICS users was identified (aOR, 1.06; 95% CI, 0.62–1.18).ConclusionThe use of ICS is associated with a reduced risk of lung cancer but not of laryngeal cancer

Whole genome sequencing of Nontuberculous Mycobacterium (NTM) isolates from sputum specimens of co-habiting patients with NTM pulmonary disease and NTM isolates from their environment

Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources. In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal

CT and 18F-FDG PET abnormalities in contacts with recent tuberculosis infections but negative chest X-ray

Close contacts of individuals with pulmonary tuberculosis are at risk for tuberculosis infection and the development of active tuberculosis. In current contact investigations, immunologic tests (the tuberculin skin test and interferon-gamma release assay) and chest X-ray examinations are used to dichotomize contacts with Mycobacterium tuberculosis infections into those with active (X-ray abnormalities) versus latent tuberculosis (normal radiographs). This article is a critical review of computed tomographic (CT) and 18-fluorodeoxyglucose positron emission tomographic (PET) findings of incipient tuberculosis without X-ray abnormalities based on a systematic literature review of twenty-five publications. The CT and 18-fluorodeoxyglucose PET studies revealed minimal pauci-nodular infiltrations in the lung parenchyma and mediastinal lymph nodes abnormalities with metabolic uptake in approximately one-third of asymptomatic close contacts with negative chest radiographic and bacteriological/molecular results for active tuberculosis. Tuberculosis with minimal changes challenge the validity of simply dichotomizing cases of recent M. tuberculosis infections in contacts depending on the presence of X-ray abnormalities as the recent infections may spontaneously regress, remain stagnant, or progress to active tuberculosis in human and nonhuman primate studies. Whether contacts with tuberculosis with minimal changes are interpreted as having active tuberculosis or latent tuberculosis has clinical implications in terms of specific benefits and harms under the current contact management. Advanced imaging tools may help further stratify contacts intensely exposed to M. tuberculosis on a continuous spectrum from latent tuberculosis to incipient, subclinical and active tuberculosis. Identifying incipient tuberculosis would provide an opportunity for earlier and tailored treatment before active tuberculosis is established

Old age is associated with worse treatment outcome and frequent adverse drug reaction in Mycobacterium avium complex pulmonary disease

Background : The number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly increasing globally, especially in the older population. However, there is a dearth of evidence regarding the impact of aging on the treatment outcomes of NTM-PD. Methods : We analyzed consecutive patients who satisfied the diagnostic criteria for Mycobacterium avium complex (MAC)-PD and received antibiotic treatment between January 2009 and December 2020 at a tertiary referral hospital in Korea. The main outcomes were (1) long-term treatment success, defined by negative culture conversion for more than 12 months; and (2) adverse drug reactions (ADRs). Multivariable logistic regression model was used to evaluate the association between age and main outcomes. Results : A total of 614 patients (median age, 65 years, interquartile range [IQR] 57–73 years; men, 35.3%) were included. Median treatment duration (530 days, IQR 290–678 days; P for trend < 0.001) and long-term treatment success (P for trend = 0.026) decreased, whereas ADRs (P for trend < 0.001) increased significantly with age. Multivariable analyses demonstrated that age ≥ 80 years was an independent factor associated with ADRs (adjusted odds ratio [aOR] 3.29; 95% confidence interval [CI] 1.05–10.28) and worse treatment outcome (aOR 0.42; 95% CI 0.19–0.91). Conclusions : Aging is associated with worse treatment outcome and frequent ADRs of patients with MAC-PD. Individualized treatment with reduced-intensity may be a reasonable alternative for older adults

Clinical Characteristics and Risk Factors for Nosocomial Candidemia in Medical Intensive Care Units: Experience in a Single Hospital in Korea for 6.6 Years

The aim of this study was to determine candidemia incidence among patients in a medical intensive-care unit (MICU) and the associated mortality rate and to identify risk factors associated with candidemia. We retrospectively performed a 1:3 matched case-control study of MICU patients with candidemia. Controls were matched for sex, age, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Candidemia incidence was 9.1 per 1,000 admissions. The most common pathogen was Candida albicans. Crude mortality was 96% among candidemia patients and 52% among controls (P<0.001). Mortality differed significantly between the groups according to Kaplan-Meier survival analysis (P=0.024). Multivariate analysis identified the following independent risk factors for candidemia: central venous catheterization (odds ratio [OR] = 3.2, 95% confidence interval [CI]=1.2-9.0), previous steroid therapy (OR=4.7, 95% CI=1.8-12.1), blood transfusion during the same admission period (OR=6.3, 95% CI=2.4-16.7), and hepatic failure upon MICU admission (OR=6.9, 95% CI=1.7-28.4). In conclusion, we identify an additional independent risk factor for candidemia, the presence of hepatic failure on MICU admission. Therefore, increased awareness of risk factors, including hepatic failure, is necessary for the management of candidemia

Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria

Background: To date, more than 125 species of nontuberculous mycobacteria (NTM) have been identified. In this study, we investigated the frequency and clinical implication of the rarely isolated NTM from respiratory specimens. Methods: Patients with NTM isolated from their respiratory specimens between July 1, 2010 and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM not falling within the group of eight NTM species commonly identified at our institution: Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical, radiographic and microbiological data from patients with rare NTM were reviewed and analyzed. Results: During the study period, 73 rare NTM were isolated from the respiratory specimens of 68 patients. Among these, M. conceptionense was the most common (nine patients, 12.3%). The median age of the 68 patients with rare NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only once in majority of patient (64 patients, 94.1%). Among the four patients from whom rare NTM were isolated two or more times, only two showed radiographic aggravation caused by rare NTM during the follow-up period. Conclusions: Most of the rarely identified NTM species were isolated from respiratory specimens only once per patient, without concomitant clinical aggravation. Clinicians could therefore observe such patients closely without invasive work-ups or treatment, provided the patients do not have decreased host immunity towards mycobacteriaPeer Reviewe

Longitudinal changes in health-related quality of life according to clinical course among patients with non-tuberculous mycobacterial pulmonary disease: a prospective cohort study

Improvement in health-related quality of life (HRQL) has been suggested as an alternative treatment goal of non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study was performed to elucidate the longitudinal changes in HRQL using St. Georges Respiratory Questionnaire (SGRQ) among patients with NTM-PD according to their clinical course. Patients with NTM-PD who participated in Seoul National University Hospitals prospective NTM cohort were screened. Participants for whom the SGRQ score was estimated with the one-year interval for ≥ three times were included. The longitudinal trends of the SGRQ score were assessed. The impact of the clinical course on the change in the SGRQ score was elucidated using multilevel mixed-effects linear regression with a repeated-measures model. In total, 114 patients were analyzed. During the median 5-year observation period, 53 patients started anti-mycobacterial treatment and 61 patients were observed without treatment. Among the treated patients, 24 (45.2%) achieved microbiological cure. Patients who required treatment eventually had worsening SGRQ scores with time compared with patients who could be observed without treatment (P < 0.001). In cured patients, the SGRQ score decreased from 33.9 at baseline to 20.8 at 1 year post-treatment (P < 0.001), 21.3 at 2 years (P < 0.001), and 17.6 at 3 years (P < 0.001). The SGRQ scores also decreased for 2 years of treatment in patients with NTM-PD that could not be cured, although this decrease did not last for 3 years of treatment. Worsening HRQL scores were associated with the initiation of treatment and, in turn, treatment improved HRQL scores of patients with NTM-PD. This study was registered to the ClinicalTrials.gov (Identifier: NCT01616745 / registration date: June 12, 2012). The protocol was retrospectively registered

Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease

Abstract Background A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD. Methods Patients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide. Results Among the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67–88.92; 15.82, 2.38–105.33; and 17.12, 3.93–74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54–21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72–15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01–0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only. Conclusions Maintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop