Background: Asymptomatic colonization by nontuberculous mycobacteria (NTM) found in sputum isolates are commonly encountered and clinicians lack a biomarker for prognosticating the risk of transition asymptomatic colonization to active clinical disease. Chest computed tomography (CT) imaging is commonly obtained in this patient population and may serve a role for this purpose. Methods: We conducted a single-center, cross-sectional study of patients followed in the NTM clinic at our center between August 2019 and August 2020. All patients had a history of NTM isolated from their airways and were cohorted as either nontuberculous mycobacteria-pulmonary disease (NTM-PD) if they met ATS/IDSA guidelines for treatment or as nontuberculous mycobacteria-colonized (NTM-C) if they did not meet ATS/IDSA criteria for NTM treatment. Patients with a chest CT were included in the analysis and CT scans were assessed for features including bronchiectasis, nodules, and cavities. Bronchiectasis severity was calculated using the modified Reiff scoring system. Univariate analyses were conducted to compare patients with NTM-C and NTM-PD. Results: Eighty-four patients were included in the analysis and 27 were classified as NTM-C and 57 as NTM-PD. NTM-PD patients had a greater median number of lung lobes affected by bronchiectatic airways (6 [1] NTM-PD vs. 5 [3] NTM-C P=0.005) and a greater frequency of cystic bronchiectasis (17.5% NTM-PD vs. 0% NTM-PD, P=0.016). Bronchiectasis severity was higher for NTM-PD patients (7 [9] NTM-PD vs. 5 [1.5] NTM-C, P<0.001). Conclusions: Patients with NTM-PD have greater bronchiectatic airway involvement and the forms of bronchiectasis present are more severe compared with NTM-C patients. In addition, cavitation of lung parenchyma was a radiographic feature solely associated with NTM-PD. Features identified on chest CT may be useful as a prognostic biomarker for the risk of transition from NTM-C to NTM-PD.

ImportanceSepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.ObjectiveTo describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.Design, Setting, and ParticipantsThis prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.InterventionsThe intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.Main Outcomes and MeasuresCognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.ResultsAfter exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.Conclusions and RelevanceIn survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.Trial RegistrationClinicalTrials.gov Identifier: NCT03509350

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OBJECTIVES/GOALS: The Saint Georges Respiratory Questionnaire (SGRQ) is used as a patient reported outcome tool for clinical research in COPD and bronchiectasis. We established a registry and biospecimen repository of bronchiectasis patients with and without NTM and report associations between clinical phenotype and SGRQ scores. METHODS/STUDY POPULATION: Patients were recruited in a cross-sectional format from the Bronchiectasis, Cystic Fibrosis, and NTM clinics at our institution. All patients provided at least one sputum sample in the six months prior to inclusion. Clinical and epidemiologically relevant data was obtained, and blood specimens were processed and preserved. Patients were grouped based on clinical phenotype and differences in SGRQ scores were analyzed using ANOVA or Student’s t-test. Descriptive statistics are reported as means and standard deviations, p<0.05 considered significant. RESULTS/ANTICIPATED RESULTS: 72 NTM patients completed the SGRQ including 39 patients not on treatment (Colonized), 29 patients on NTM directed antibiotics, and 4 patients whose infection was cured in the past year. Among patients on treatment, 14 were treatment refractory (positive cultures beyond 12 months of therapy). The mean age of all NTM patients was 59.5±17.6 and 80.5% were female. Mean SGRQ Total scores were significantly higher among patients receiving treatment compared to patients considered colonized (35.7± 22.0 colonized group versus 48.8± 15.8 treatment group, p = 0.011). The SGRQ subdomain scores including Impacts (26.2± 26.2 colonized group versus 42.5± 17.0 treatment group, p = 0.01) and Activities (41.7± 31.8 colonized group versus 59.3± 24.5 treatment group, p = 0.018) were also significantly different between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed a cross sectional cohort of NTM patients and assessed associations between clinical phenotype and SGRQ score. Preliminary data suggests that female sex, treatment status, and therapeutic duration are associated with higher SGRQ scores. We intend to continue to assess the potential for specific SGRQ questions to be used for quantifying disease symptom severity for NTM patients.

OBJECTIVES/GOALS: Non-tuberculous mycobacteria (NTM) is an emerging infection in the United States. Therapeutic development is impaired in NTM due to lack of biomarkers associated with disease activity and treatment response. To address this, we established a cross-sectional patient registry and biorepository from NTM patients. METHODS/STUDY POPULATION: Beginning August 2019 patients were recruited in a cross-sectional format from the bronchiectasis and NTM clinics at our institution. All patients provided at least one sputum sample in the six months prior to inclusion. Clinical and epidemiologically relevant data was obtained, patient reported outcome measures including the SGRQ were provided, and blood specimens were processed and preserved. Patients were grouped based on clinical phenotype and descriptive statistics were reported as means and standard deviations. Serum inflammatory profiles will be analyzed using standard Luminex assays. RESULTS/ANTICIPATED RESULTS: 72 patients with prior NTM isolation from sputum have been recruited including 28 patients that do not meet ATS guidelines for NTM treatment (colonized), 29 patients are currently receiving treatment, and 15 patients that have a history of completing therapy. Among all NTM patients, the mean age was 59.5 ±17.6 years and 80.8% were female. The mean FEV1 percent predicted among these patients was 68.0 ±21.5% and mean BMI was 22.35 ±4.1. The most common mycobacterial species isolated was Mycobacterium Avium Complex (47%). The mean SGRQ total score was 40.2 ±20.3 among all NTM patients. We plan to perform standard Luminex assays to identify inflammatory profiles associated with disease phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed a cross sectional cohort of NTM patients including a registry of clinically relevant data for phenotyping and an accompanying biospecimen repository. Our long-term goal is to identify biomarkers indicative of disease activity and treatment response using these components.