The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity

BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment.

1396. The Incremental Hospitalization Burden Associated with Nontuberculous Mycobacterial Lung Disease(NTMLD) among Patients with Chronic Obstructive Pulmonary Disease (COPD) in Japan

Background NTMLD is a life-threatening pulmonary infection with increasing incidence and prevalence in Japan. It is associated with progressive lung damage and increased healthcare use. Many patients with NTMLD have comorbid respiratory conditions such as COPD. Treatment of NTMLD in patients with COPD is difficult, however there is limited data on the incremental burden that NTMLD adds to underlying COPD. We assessed the incremental burden associated with NTMLD in Japanese patients with COPD by comparing their hospitalizations to matched COPD patients without NTMLD. Methods A retrospective cohort study was conducted using claims data provided by the Japan Medical Data Center (2015-2020). COPD patients with NTMLD were matched 1:3 to COPD patients without NTMLD (controls). Hospitalizations (all-cause, respiratory-related, and COPD-related) were accrued over a 1-year follow-up period after NTMLD diagnosis (index). Incremental burden of NTMLD was assessed by comparing hospitalizations between COPD patients with NTMLD and controls with univariate and multivariate analyses adjusting for comorbidities during 1-year pre-index period. Results A total of 492 COPD patients with NTMLD were matched by age and sex to 1476 controls. Mean (SD) age on index date was 56.6 (10.3) years and 61.4% were females. Compared to controls, NTMLD patients had higher prevalence of some pulmonary symptoms and comorbidities such as hemoptysis (11% vs 2%), dyspnea (1.6% vs 0.6%) and lung cancer (7% vs 4%). In univariate analyses, a higher percent of COPD patients with NTMLD had hospitalizations compared to controls (Fig 1A); the unadjusted annual hospitalization rates were also higher among patients with NTMLD (Fig 2A). Multivariate regressions after adjusting for pre-index comorbidities showed COPD patients with NTMLD were 1.9 times more likely to have an all-cause hospitalization, 2.8 times more likely to have a respiratory hospitalization, and 3.0 times more likely to have a COPD-related hospitalization (Fig 1B). Conclusion COPD patients with NTMLD had a higher burden of hospitalization than COPD patients without NTMLD. The statistically significantly incremental burden associated with NTMLD in patients with COPD highlights the acute need for appropriate management of NTMLD in Japan. Disclosures Naoki Hasegawa, MD, PhD, Insmed Incorporated (Consultant, Scientific Research Study Investigator)Janssen Pharmaceuticals Inc (Consultant, Scientific Research Study Investigator) Kozo Morimoto, MD, Insmed Incorporated (Consultant) Ping Wang, PhD, Insmed Incorporated (Employee) Lu Zhang, PhD, Panalgo (Employee, Other Financial or Material Support, Lu Zhang is an employee of Panalgo which provides the analytic platform Instant Health Data that is used by Insmed) Mariam Hassan, PhD, B. Pharm, Insmed Incorporated (Employee) Anjan Chatterjee, MD, MPH, Insmed Incorporated (Employee)

A Case Report on Managing the Side Effects of Anti-tuberculosis Drugs for Nontuberculous Mucobacteriosis (NTM) by Concurrently using Traditional Korean Medicine and Antibiotics

Objectives: This study investigated the effect of combined Korean medical treatment and antibiotics on a patient diagnosed with nontuberculous mycobacterial lung disease.Methods: The patient had been treated with antibiotics since July 2020 concurrently with Maekmoondong-tang, Banhasasim-tang, Gwakhyangjunggi-san and Bojungikgi-tang. The improvement of symptoms was evaluated using scores for the numerical rating scale (NRS), the Medical Research Council (MRC) dyspnea scale, C-reactive protein (CRP) levels, and computed tomography (CT).Results: Following treatment, the NRS, MRC dyspnea scale and CT images significantly improved. Also, CRP levels remained in the normal range during treatment.Conclusions: Traditional Korean medical treatment combined with antibiotics could be effective for treating patients with nontuberculous mycobacterial lung disease.

Inhaled Corticosteroids Increase Risk of Nontuberculous Mycobacterial Lung Disease: A Nested Case-Control Study and Meta-analysis

Studies on use of inhaled corticosteroids (ICS) and the risk of nontuberculous mycobacterial lung disease (NTM-LD) are limited and have some conflicting results. We recruited 1235 NTM-LD patients and found that ICS use within 1 year was associated with increased NTM-LD, and the risk increased with elevated ICS dose and cumulative duration. Discontinuation of ICS use for more than 120 days could reduce the risk of NTM-LD to an insignificant level. For NTM species, the development of NTM-LD by ICS was highest for Mycobacterium kansasii lung disease. The pooled results of the meta-analysis showed that ICS use might increase the risk of NTM-LD with dose response in medium and high dose of daily ICS. In addition, budesonide had a smaller impact on the risk of NTM-LD than other ICS medications. The present study and meta-analysis provide evidence for ICS adjustment, including dose, discontinuation effect, and medications to possibly reduce the risk of NTM-LD.