Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

Usefulness of the mini nutritional assessment short-form for evaluating nutritional status in patients with nontuberculous mycobacterial pulmonary disease: a prospective cross-sectional study.

BACKGROUND: Although the Mini Nutritional Assessment (MNA) is recognized as a useful tool for evaluating nutritional status in patients with various diseases, its applicability in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) remains undetermined. METHODS: We designed a prospective cross-sectional study to investigate whether the MNA Short-Form (MNA-SF) score can serve as a screening tool to assess the nutritional status of patients with NTM-PD. The MNA-SF was conducted upon patient enrollment, and correlation analyses were performed to compare MNA-SF scores with other nutritional measurements and disease severity. Multivariable logistic regression analyses were conducted to evaluate the association between MNA-SF scores and NTM-PD severity. RESULTS: The 194 patients with NTM-PD included in the analysis had a median age of 65.0 (59.0-69.0) years; 59.3% (n = 115) had low MNA-SF scores (< 12). The low MNA-SF group exhibited a lower body mass index (19.7 vs. 22.4 kg/m2, p < 0.001) and fat-free mass index (14.7 vs. 15.6 kg/m2, p < 0.001) than the normal MNA-SF group, as well as higher incidences of sarcopenia (20.0% vs. 6.3%, p = 0.008) and adipopenia (35.7% vs. 5.1%, p < 0.001). However, no significant differences in calorie and protein intakes were observed between the two groups. Low MNA-SF scores were associated with radiographic severity (adjusted odds ratio 2.72, 95% confidence interval 1.38-5.36) but not with forced vital capacity. CONCLUSIONS: The MNA-SF can effectively assess the nutritional status of patients with NTM-PD and can serve as an important clinical indicator in NTM-PD where treatment timing is determined by clinical judgment.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.

BACKGROUND: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. METHODS: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. FINDINGS: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. INTERPRETATION: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. FUNDING: Korea Disease Control and Prevention Agency, South Korea.

Nationwide Treatment Outcomes of Patients With Multidrug/Rifampin-Resistant Tuberculosis in Korea, 2011-2017: A Retrospective Cohort Study (Korean TB-POST).

BACKGROUND: The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. METHODS: We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. RESULTS: A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P < 0.001). In contrast, TB-related death rate was not significantly changed (P = 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2-32.4) after completion treatment. CONCLUSION: The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.

Heterogeneous effects of COVID-19 control measures on tuberculosis in South Korea: an analysis of case notification data.

Coronavirus disease (COVID-19) responses such as social distancing practices can decrease health care access and tuberculosis (TB) notification, particularly among individuals aged 60 years or older. Conversely, they can increase TB notification among younger individuals. These results may be attributable to household transmission and the similarity of TB respiratory symptoms to COVID-19.

Sarcopenia is associated with cardiovascular risk in men with COPD, independent of adiposity.

BACKGROUND: Sarcopenia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its relationship with chronic obstructive pulmonary disease (COPD) has not been fully determined. This study is aimed to investigate the association between sarcopenia and risk for ASCVD in patients with COPD, independent of central obesity and fat mass. METHODS: Data regarding 704 men with COPD (mean age: 63.4 years) were extracted from the 2008 to 2011 Korean National Health and Nutrition Examination Surveys. Sarcopenia index and fat mass were assessed using dual-energy X-ray absorptiometry. Sarcopenia was defined according to the presence of sarcopenia index values < 1 standard deviation from the cutoff (0.774) among the study participants. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk > 20%. RESULTS: The quartile-stratified sarcopenia index was negatively associated with ASCVD risk (P < 0.001). ASCVD risk and prevalence of high ASCVD risk were significantly greater in sarcopenic participants than in non-sarcopenic participants, regardless of central obesity and fat mass (all P < 0.001). Multivariate regression analyses demonstrated an independent association between sarcopenia and ASCVD risk (estimated ± standard error = 3.63 ± 0.77%, P < 0.001) and high ASCVD risk (odds ratio [OR] = 2.32, 95% confidence interval [CI] 1.05-5.15, P = 0.039). Furthermore, sarcopenia was an independent factor for high ASCVD risk in participants with moderate to very severe airflow limitation (OR = 2.97, 95% CI 1.06-8.36, P < 0.001). CONCLUSIONS: Sarcopenia was significantly associated with an increased risk for ASCVD in men with COPD, independent of central obesity and fat mass. High ASCVD risk was significantly associated with sarcopenia, particularly in participants with moderate to very severe airflow limitation.

Treatment outcome of continuation of intravenous amikacin for Mycobacterium abscessus pulmonary disease with a persistent culture positivity after the treatment initiation.

INTRODUCTION: Whether prolonged intravenous amikacin treatment would lead to better treatment results in patients with Mycobacterium abscessus subspecies abscessus (M. abscessus) pulmonary disease (PD) is unknown. We investigated the efficacy of continued amikacin treatment for the microbiological outcome of M. abscessus PD patients with persistent culture positivity after treatment initiation. METHODS: We retrospectively evaluated 62 patients with M. abscessus PD who were treated with intravenous amikacin and beta-lactams along with a macrolide-based regimen at 3 tertiary referral centers in South Korea. The intravenous antibiotic treatment duration was determined by the attending physician. RESULTS: The median treatment durations with amikacin and beta-lactam in the 62 patients were 25.1 and 8.2 weeks, respectively. The overall microbiological cure rate was 29.0%. Among the 62 patients, 44 showed persistent culture positivity at 8 weeks after treatment with an amikacin-containing multidrug regimen. The median parenteral amikacin treatment duration after 8 weeks in these patients was 18.0 weeks. The conditional probability of microbiological cure with continuation of the amikacin-containing regimen in these patients was 18.2% (95% confidence interval 8.2-32.7). Additionally, the conditional probability of microbiological cure in the 34 patients with persistent culture positivity at 12 weeks was 8.8% (95% confidence interval 1.9-23.7). After 16 weeks, the conditional probability of microbiological cure decreased further, reaching 0% at 28 weeks after treatment initiation. CONCLUSION: The continuation of intravenous amikacin therapy was usually not followed by culture conversion in M. abscessus PD patients with persistent sputum culture positivity after treatment initiation.

Comorbidities of nontuberculous mycobacteria infection in Korean adults: results from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database.

BACKGROUND: The global prevalence and incidence of nontuberculous mycobacteria (NTM) infection are increasing. However, the prevalence of NTM infection-associated comorbidities remains understudied. Thus, we investigated the comorbidities associated with NTM infection using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database of the National Health Insurance Service (NHIS). METHODS: In this case-control study, patients with NTM infection and controls aged 20-89 years of age were matched 1:4 by sex, age, region, and income. A total of 26 comorbidities were selected based on previous reports and claims data analysis. The distribution of comorbidities was compared between patients with NTM infection and controls by sex and age using logistic regression analysis. RESULTS: In total, 893 patients (379 men and 514 women) with NTM infection (mean age, 56.1 years) and 3,572 controls (mean age, 55.6 years) were included. The odds ratio for prevalence of respiratory diseases, metabolic diseases, musculoskeletal disorders, gastrointestinal diseases, skin diseases, mental diseases, and neoplasms was significantly higher in patients with NTM infection than in the control group. Among comorbid diseases, the odds ratios (ORs) for the prevalence of the respiratory diseases such as bronchiectasis (OR [95% confidence interval (CI)]: 26.79 [19.69-36.45]) and interstitial pneumonitis (OR [95% CI]: 15.10 [7.15-31.89]) were the highest. No significant differences were observed in NTM infection-related comorbidities between men and women. In the younger age group (20-39 years old), the prevalence of respiratory and systemic diseases such as hypertension and diabetes was higher in the patient group than in the control group. CONCLUSIONS: NTM infection is associated with several respiratory and systemic diseases that should be considered when providing medical care to patients with NTM infection.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

The relationship between cognitive function and competence in inhaler technique in older adults with airway disease.

Cognitive impairment has high prevalence in older adults with airway diseases, and may influence their competence in inhaler use, thereby negatively affecting patient prognosis. We aimed to evaluate the relationship between cognitive function and competence in inhaler technique. We enrolled 108 inhaler naïve older adults (≥60 years) with airway disease in this prospective observational study and performed the Korean version of the Mini-Mental State Examination (K-MMSE). After explaining the inhaler technique, we scored its competence. While the total K-MMSE score was unrelated to the inhaler score, the orientation for place (estimates=0.62, p = 0.009), registration (estimates=0.988, p = 0.037), and recall (estimates=0.161, p = 0.048) were positively associated with the score. Low K-MMSE scores were associated with lower odds ratio for the competence of the "exhale" step (adjusted odds ratio= 0.23, p = 0.018). Thus, a K-MMSE-mediated evaluation of cognitive function in older adults with airway disease can be a useful tool to predict inhaler competence.

Deep Learning to Determine the Activity of Pulmonary Tuberculosis on Chest Radiographs.

Background Determining the activity of pulmonary tuberculosis on chest radiographs is difficult. Purpose To develop a deep learning model to identify active pulmonary tuberculosis on chest radiographs. Materials and Methods Chest radiographs were retrospectively gathered from a multicenter consecutive cohort with pulmonary tuberculosis who were successfully treated between 2011 and 2017, along with normal radiographs to enrich a negative class. The pretreatment and posttreatment radiographs were labeled as positive and negative classes, respectively. A neural network was trained with those radiographs to calculate the probability of active versus healed tuberculosis. A single-center consecutive cohort (test set 1; 89 patients, 148 radiographs) and data from one multicenter randomized controlled trial (test set 2; 366 patients, 3774 radiographs) were used to test the model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model and of the four expert readers. Results In total, 6654 pre- and posttreatment radiographs from 3327 patients (mean age ± standard deviation, 55 years ± 19; 1884 men) with pulmonary tuberculosis and 3182 normal radiographs from as many patients (mean age, 53 years ± 14; 1629 men) were gathered. For test set 1, the model showed a higher AUC (0.83; 95% CI: 0.73, 0.89) than one pulmonologist (0.69; 95% CI: 0.61, 0.76; P < .001) and performed similarly to the other readers (AUC, 0.79-0.80; P = .14-.23). For 200 randomly selected radiographs from test set 2, the model had a higher AUC (0.84) than the pulmonologists (0.71 and 0.74; P < .001 and .01, respectively) and performed similarly to the radiologists (0.79 and 0.80; P = .08 and .06, respectively). The model output increased by 0.30 on average with a higher degree of smear positivity (95% CI: 0.20, 0.39; P < .001) and decreased during treatment (baseline, 3 months, and 6 months: 0.85, 0.51, and 0.26, respectively). Conclusion A deep learning model performed similarly to radiologists for accurately determining the activity of pulmonary tuberculosis on chest radiographs; it also was able to follow posttreatment changes. © RSNA, 2021 Online supplemental material is available for this article.

Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.

BACKGROUND: Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer. METHODS: 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses. RESULTS: In total, 84 patients were prospectively analyzed, of which 59 showed low (< 10%), and 25 showed high (≥ 10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group. CONCLUSION: The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.

Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005.

BACKGROUND: Tuberculosis (TB) has been a major public health problem in South Korea. Although TB notification rate in Korea is gradually decreasing, still highest among the member countries of the Organization for Economic Cooperation and Development. To effectively control TB, understanding the TB epidemiology such as prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) are important. This study aimed to identify the prevalence of LTBI and ARI among South Korean health care workers (HCWs) based on their interferon-gamma release assays (IGRA). METHODS: This was single center, cross-sectional retrospective study in a tertiary hospital in South Korea. We performed IGRA in HCWs between May 2017 and March 2018. We estimated ARI based on IGRA results. Logistic regression model was used to identify factors affecting IGRA positivity. RESULTS: A total of 3233 HCWs were analyzed. Median age of participants was 38.0 and female was predominant (72.6%). Overall positive rate of IGRA was 24.1% and IGRA positive rates age-group wise were 6.6%, 14.4%, 34.3%, and around 50% in the age groups 20s, 30s, 40s, and 50s and 60s, respectively. The ARIs was 0.26-1.35% between 1986 and 2005; rate of TB infection has gradually decreased in the last two decades. Multivariable analysis indicated that older age, healed TB lesion in x-ray, and male gender were risk factors for IGRA positivity, whereas working in high-risk TB departments was not. CONCLUSIONS: Results showed that ARI in South Korean HCWs gradually decreased over two decades, although LTBI remained prevalent. Our results suggest that the LTBI test result of HCWs might be greatly affected by age, rather than occupational exposure, in intermediate TB burden countries. Thus, careful interpretation considering the age structure is required.

Effectiveness of pirfenidone in idiopathic pulmonary fibrosis according to the autoantibody status: a retrospective cohort study.

BACKGROUND: Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear. METHODS: We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies. RESULTS: We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were - 34.4 and - 112.2 mL (p = 0.168) in forced vital capacity (FVC), and - 0.53 and - 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively. CONCLUSIONS: Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD). METHODS: We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. RESULTS: Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14-30%), and the one-year all-cause mortality was 10% (95% CI, 5-20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types. CONCLUSIONS: Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.

Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients.

BACKGROUND: Sarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients. METHODS: We retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality. RESULTS: Male patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913-0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856-1.121; P = 0.766). CONCLUSIONS: Low skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF. TRIAL REGISTRATION: The research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4-2018-0454).

Prevalence, incidence, and mortality of nontuberculous mycobacterial infection in Korea: a nationwide population-based study.

BACKGROUND: Epidemiologic characteristics of nontuberculous mycobacterial (NTM) disease remain largely unknown. The objective of this study was to evaluate incidence, prevalence, and mortality of NTM infection in a large nationwide population-based cohort in Korea. METHODS: Data of the National Health Insurance Service database, an extensive health-related database including most Korean residents, were used. Adults with a primary diagnosis of NTM as determined by International Classification of Disease-Tenth Revision coding (A31) were identified between 2003 and 2016. Incidence, prevalence, and mortality of NTM infection were analyzed. RESULTS: A total of 46,194 individuals had a primary diagnosis of NTM infection. Their mean age was 55.8 years. Of these subjects, 61.1% were females. Annual age-adjusted incidence and prevalence of NTM infection tended to increase rapidly from 2003 to 2016. Age-adjusted incidence and prevalence was 17.9 and 33.3 per 100,000 population in 2016. The incidence and prevalence were higher in females and the elderly. The 5-year mortality rate in the population with NTM infection was 17.8%. The standardized mortality ratio of patients with NTM infection to the general population was 2.16 (95% confidence interval: 2.10 to 2.22). CONCLUSIONS: This large population-based study showed that the incidence and prevalence of NTM infection in Korea increased rapidly from 2003 to 2016. They were higher in women and the elderly. The mortality rate in the population with NTM infection was higher than that in the general population.