Clinical outcomes of mild to moderate coronavirus disease 2019 patients treated with Regdanvimab in delta-variant outbreak: Retrospective cohort study.

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation.

Impact of lung cancer screening with low-dose chest computed tomography on an older population: a retrospective cohort study.

Background: The older population is at high risk of lung cancer (LC). However, the importance of lung cancer screening (LCS) in this population is rarely investigated. Herein, we evaluated the effect of LCS with low-dose computed tomography (LDCT) in the older population. Methods: This retrospective cohort study was conducted in a single center and included patients aged 70-80 years who had undergone LCS with LDCT. They were categorized into the early 70s (70-74 years) and late 70s (75-80 years) groups based on their age. Using propensity score matching, the control group included patients with non-screening-detected LC from an LC cohort. LC detection, characteristics, and treatment were compared between the early and late 70s groups and between screening-detected LC and non-screening-detected LC. Results: The study included 1,281 participants who underwent LDCT for LCS, of whom 1,020 were in their early 70s and 261 in their late 70s. Among the screening groups, 87.7% of the patients were ever-smokers. The overall LC detection rate was 2.8%. Interestingly, the LC detection rate in the late 70s group was similar to that in the early 70s group (3.4% vs. 2.7%, P=0.485). Furthermore, the incidence of LC was 6.1 cases and 8.3 cases per 1,000 person-years in the early 70s and late 70s groups, respectively (P=0.428). When comparing LC characteristics, patients with screening-detected LC showed a higher proportion of stage I LC (52.8% vs. 30.6%, P=0.010) and a lower proportion of stage IV LC (19.4% vs. 42.2%, P=0.010) than those with non-screening-detected LC. Moreover, 80.6% of patients with screening-detected LC received appropriate tumor reduction treatment based on the cancer stage. Conclusions: In the older population, LCS using LDCT showed remarkable detection of LC, with a higher proportion of cases detected at an early stage.

Comparing Inhaler Use Technique Based on Inhaler Type in Elderly Patients with Respiratory Disease.

BACKGROUND: The aim of this study was to investigate inhaler device handling in elderly patients. Inhaler devices with respect to misuse and error correction were also compared. METHODS: Inhaler use technique was assessed using standardized checklists at the first visit and 3-month follow-up visit after retraining. The primary outcome was difference in the acceptable use ratio among inhaler devices. Secondary outcomes included differences in error correction, the most common step of misuse, and factors affecting the accuracy of inhaler use. RESULTS: A total of 251 patients (mean age, 76.4 years) were included. The handling of 320 devices was assessed in the study. All patients had been trained before. However, only 24.7% of them used inhalers correctly. Proportions of acceptable use for Evohaler, Respimat, Turbuhaler, Ellipta, and Breezhaler/Handihaler were 38.7%, 50.0%, 61.4%, 60.8%, and 43.2%, respectively (p=0.026). At the second visit, the acceptable use ratio had increased. There were no significant differences among inhaler types (Evohaler, 63.9%; Respimat, 86.1%; Turbuhaler, 74.3%; Ellipta, 64.6%; and Breezhaler/Handihaler, 65.3% [p=0.129]). In multivariate analysis, body mass index, Turbuhaler, and Ellipta showed positive correlations with acceptable use of inhalers, whereas Chronic Obstructive Pulmonary Disease Assessment Test score showed a negative correlation. CONCLUSION: Although new inhalers have been developed, the accuracy of inhaler use remains low. Elderly patients showed more errors when using pressurized metered-dose inhalers than using dry powder inhalers and soft-mist inhalers. However, there were no significant differences in misuse among inhaler devices after individual training. Results of this study suggests that repeat training is more important than inhaler type.

Impact of body mass index on development of nontuberculous mycobacterial pulmonary disease.

The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) have been increasing worldwide. The risk of NTM-PD may be higher in undernourished populations. In this study, we tried to elucidate the impact of body mass index (BMI) and its change on development of NTM-PD.We performed a retrospective cohort study including South Koreans aged >40 years who underwent biennial National Health Insurance System (NHIS) health check-ups in both 2005 and 2009 or 2006 and 2010. We monitored eligible individuals from the study initiation date (NHIS health check-up date in 2009 or 2010) until the diagnosis of NTM-PD or until December 31, 2017. Enroled individuals were classified based on BMI at initiation date. By calculating hazard ratios, we compared NTM-PD incidence per 100 000 person-years by BMI group and by BMI change.A total of 5 670 229 individuals were included in the final analysis. Compared with the BMI <18.5 kg·m-2 group, the incidence of NTM-PD gradually decreased with increased BMI (adjusted hazard ratio 0.38, 95% confidence interval (CI) 0.35-0.42 for BMI 18.5-22.9; 0.17, 95% CI 0.15-0.19 for BMI 23-24.9; 0.1, 95% CI 0.09-0.11 for BMI 25-29.9; and 0.1, 95% CI 0.07-0.13 for BMI ≥30). A BMI decrease of ≥1 kg·m-2 over 4 years increased the incidence of NTM-PD (adjusted hazard ratio 1.08, 95% CI 1.01-1.16) whereas a BMI increase of ≥1 kg·m-2 decreased the incidence of NTM-PD (adjusted hazard ratio 0.77, 95% CI 0.71-0.83).In conclusion, BMI was inversely related to development of NTM-PD and weight loss increased the risk of NTM-PD.

Evolution of Interferon-Gamma Release Assay Results and Submillisievert Chest CT Findings among Close Contacts of Active Pulmonary Tuberculosis Patients.

BACKGROUND: Latent tuberculosis (TB) infection among TB contacts is diagnosed using plain chest radiography and interferon-gamma release assays (IGRAs). However, plain chest radiographs often miss active TB, and the results of IGRA could fluctuate over time. The purpose of this study was to elucidate changes in the results of the serial IGRAs and in the findings of the serial submillisievert chest computed tomography (CT) scans among the close contacts of active pulmonary TB patients. METHODS: Patients age 20 or older with active pulmonary TB and their close contacts were invited to participate in this study. Two types of IGRA (QuantiFERON-TB Gold In-Tube assay [QFT-GIT] and the T-SPOT.TB test [T-SPOT]) and submillisievert chest CT scanning were performed at baseline and at 3 and 12 months after enrollment. RESULTS: In total, 19 close contacts participated in this study. One was diagnosed with active pulmonary TB and was excluded from further analysis. At baseline, four of 18 contacts (22.2%) showed positive results for QFT-GIT and T-SPOT; there were no discordant results. During the follow-up, transient and permanent positive or negative conversions and discordant results between the two types of IGRAs were observed in some patients. Among the 17 contacts who underwent submillisievert chest CT scanning, calcified nodules were identified in seven (41.2%), noncalcified nodules in 14 (82.4%), and bronchiectasis in four (23.5%). Some nodules disappeared over time. CONCLUSION: The results of the QFT-GIT and T-SPOT assays and the CT images may change during 1 year of observation of close contacts of the active TB patients.

The clinical impact of drug-induced hepatotoxicity on anti-tuberculosis therapy: a case control study.

BACKGROUND: There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB. METHODS: In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients. RESULTS: Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients. CONCLUSION: DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.

Prognostic Implication of Adrenocortical Response during the Course of Critical Illness.

BACKGROUND: Critical illness-related corticosteroid insufficiency (CIRCI) and adrenocorticotropic hormone (ACTH)-cortisol dissociation are hormonal conditions frequently observed in patients in the intensive care unit (ICU). The aim of this study was to evaluate the association between ACTH-cortisol dissociation and clinical outcomes of critically ill patients. METHODS: We retrospectively reviewed the medical records of 94 ICU patients who underwent two rapid cosyntropin tests during hospital admission and compared the clinical aspects of patients with and without ACTH-cortisol dissociation. ACTH-cortisol dissociation was defined as plasma ACTH and serum cortisol concentrations of <22 pmol/L and >600 nmol/L, respectively. RESULTS: Dissociation was present in 30 of the 94 patients (31.9%). Patients with ACTH-cortisol dissociation in the initial test had significantly higher hospital mortality rate than those in the control group (55% vs. 25.7%, P=0.013) There was no difference in hospital mortality between patients classified as having CIRCI and those who were not. In multivariate adjusted Cox regression analysis, the mortality risk was higher in the group with ACTH-cortisol dissociation (hazard ratio, 2.98; 95% confidence interval, 1.34 to 6.63; P=0.007). Patients with dissociation in two consecutive stimulation tests showed the highest hospital mortality rate among groups classified according to stimulation test results (100% vs. 31.3%). CONCLUSIONS: The hospital mortality was higher in ICU patients diagnosed with ACTH-cortisol dissociation. It is clinically feasible to evaluate the presence of ACTH-cortisol dissociation by analyzing rapid ACTH stimulation test results in critically ill patients.

Evaluation and treatment of latent tuberculosis infection among healthcare workers in Korea: A multicentre cohort analysis.

OBJECTIVE: Healthcare workers (HCWs) are one of the target groups for systematic testing and treatment of latent tuberculosis infection (LTBI) in a setting of low TB incidence. We performed this study to describe the testing of HCWs for LTBI and analyse the acceptance and completion of treatment of LTBI. METHODS: This retrospective cohort study was conducted in four university-affiliated hospitals between January 1 and December 31, 2018. HCWs with positive interferon-gamma release assay (IGRA) during LTBI screening were analysed. We assessed the acceptance and completion of LTBI treatment. RESULTS: Overall, 893 HCWs were IGRA positive. Among them, 609 HCWs visited the clinic for evaluation of LTBI. Of 609 HCWs who were evaluated, 302 (49.6%) were offered treatment for LTBI. The proportion of acceptance for treatment was 64.5% (195 of 302 HCWs). The treatment course was completed by 143 of 195 HCWs (73.3%). Three months of isoniazid and rifampin (3HR) was used in 137 HCWs (70.3%) and 4 months of rifampin (4R) in 58 (29.7%). 72 HCWs (36.9%) experienced at least one adverse drug events, but there was no different characteristics between completer and non-completer. CONCLUSION: The acceptance and completion of LTBI treatment were unsatisfactory. Subjective perspective regarding obstacles to treatment of LTBI needs to be explored to increase compliance to LTBI treatment.

Effect of intensivist involvement on clinical outcomes in patients with advanced lung cancer admitted to the intensive care unit.

PURPOSE: Intensive care unit (ICU)-related mortality for lung cancer is ranked highest among the solid tumors and little information exists on the role of intensivists on clinical outcomes. This study aimed to elucidate the intensivist's contribution toward clinical outcomes. MATERIALS AND METHODS: Data of advanced lung cancer patients, including stage IIIB or IV non-small cell lung cancer and extensive-stage small cell lung cancer, admitted to the ICU from 2005 to 2016 were analyzed. Multivariate logistic regression was performed to determine variables associated with ICU and in-hospital mortality. Autoregressive integrated moving average (ARIMA) for time-series was used to assess the intensivist's impact. RESULTS: Of 264 patients, 85 (32.2%) were admitted to the ICU before and 179 (67.8%) after organized intensive care introduction in 2011. Before and after 2011, the changes observed were as follows: ICU mortality rate, 43.5% to 40.2%, respectively (p = 0.610); hospital mortality rate, 82.4% to 65. 9% (p = 0.006). The duration of ICU and hospital stay decreased after 2011 (14.5±16.5 vs. 8.3 ± 8.6, p < 0.001; 36.6 ± 37.2 vs. 22.0 ± 19.6, p < 0.001). On multivariate analysis, admission after 2011 was independently associated with decreased hospital mortality (Odds ratio 0.42, 95% confidence interval 0.21-0.77, p = 0.006). In ARIMA models, intensivist involvement was associated with significantly reduced hospital mortality. (Estimate -17.95, standard error 5.31, p = 0.001). CONCLUSION: In patients with advanced lung cancer, organized intensive care could contribute to improved clinical outcomes.

Clinical impacts of the classification by 2017 GOLD guideline comparing previous ones on outcomes of COPD in real-world cohorts.

PURPOSE: While GOLD classification has been revised, its clinical impacts on outcomes of COPD patients have not been widely evaluated in real-world cohorts. MATERIALS AND METHODS: According to 2007, 2013, and 2017 GOLD classifications, distribution and clinical characteristics of group-shifted patients and the risk of acute exacerbation were analyzed in combined Korean COPD cohorts. Future risk for annual moderate-to-severe exacerbation was estimated as incidence rate ratio (IRR) and compared by groups. RESULTS: Among 1,880 COPD patients, in GOLD 2017 classification, groups B and A were increased to 61.2% and 22.2% of total population, while group C was shrunken to 2.2% and patients with higher risk were decreased (16.6% in GOLD 2017 vs 44.7% in GOLD 2013). The kappa coefficient of agreement of both systems was 0.581 (agreement 71.7%). Groups B and D showed higher IRR of moderate-to-severe exacerbation than group A (IRR 2.4 and 5.3 respectively, P<0.001), whereas group C was not different from group A. When groups C and D were combined, the IRR for acute exacerbation for each group showed good linear trends (2.5 [1.6-3.7] for group B and 4.8 [3.0-7.7] for combined group [C+D], P<0.001). CONCLUSIONS: In the revised GOLD 2017 system, COPD patients with higher risk were much decreased in Korean cohorts, and group C was negligible in size and clinical impacts on expecting future exacerbation. Serial increase in the risk for exacerbation was more concrete and predictable when group C was combined with group D.

Differences in prevalence of asthma-COPD overlap according to different criteria.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases. Overlap in the clinical features of these 2 diseases is observed in many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been proposed. However, the definition of ACO and the clinical significance remains to be determined.We evaluated the prevalence and risk of acute exacerbation in ACO among Korean COPD patients as defined by modified Spanish criteria and American Thoracic Society (ATS) Roundtable criteria.The prevalence of ACO was 47.7% (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable criteria. ACO, regardless of criteria, did not significant affect the exacerbation risk during at least 1-year follow-up period.Substantial discrepancies were found in the prevalence and outcome of ACO according to different diagnostic criteria, which would compromise implementation of ACO before the definition is established.

Pulmonary Histoplasmosis Identified by Video-Assisted Thoracic Surgery (VATS) Biopsy: a Case Report.

Histoplasmosis is a common endemic mycosis in North, Central, and South America, but Korea is not known as an endemic area. We treated an immunocompetent Korean patient who had histoplasmosis. A 65-year-old Korean man presented with multiple pulmonary clumps of tiny nodules in the both lungs. He had been diagnosed 40 years earlier with pulmonary tuberculosis (TB) and a fungus ball had been diagnosed 4 years earlier. He denied any history of overseas travel. The patient visited our hospital with dyspnea, blood-tinged sputum, and weight loss, which had appeared 2 months earlier. The patient underwent video-assisted thoracic surgery (VATS) lung biopsy. The biopsy sample showed necrotizing granuloma and the presence of multiple small yeast-like fungi. Tissue culture confirmed Histoplasma capsulatum, and he was finally diagnosed with pulmonary histoplasmosis. Therapy was initiated with 200 mg itraconazole orally once per day. The symptoms disappeared 1 week after the start of treatment. After 4 months, low-dose chest computed tomography showed improvement in the ground glass opacity and size of the lung lesions. In conclusion, we report a case of an immunocompetent patient who developed histoplasmosis in Korea. When a patient shows unexplainable progressive infiltrative lung lesions, histoplasmosis should be considered as one of differential diagnoses although Korea is not an endemic area.

Clinical implications of blood eosinophil count in patients with non-asthma-COPD overlap syndrome COPD.

BACKGROUND: Recent studies that assessed the relevance of the blood eosinophil count as a biomarker in patients with COPD may have overestimated it because they included patients with asthma-COPD overlap syndrome (ACOS). We investigated the clinical implications of the blood eosinophil count in patients with non-ACOS COPD. PATIENTS AND METHODS: From a Korean COPD Subtype Study (KOCOSS) cohort, we selected patients with non-ACOS COPD after excluding ACOS patients according to Spanish criteria. Clinical characteristics and the incidence of moderate-to-severe exacerbation were compared among the four groups stratified according to the quartiles of blood eosinophil percent and count. RESULTS: Of the KOCOSS cohort of 1,132 patients with COPD, 467 non-ACOS COPD patients (41.2%) with data of blood eosinophil count remained after excluding those with ACOS based on the Spanish definition. There was no difference in clinical characteristics among groups classified according to the quartiles of eosinophil percent and count. On multivariate logistic regression, eosinophil quartiles in percent and absolute count were not associated with the incidence of moderate-to-severe acute exacerbations of COPD (AECOPD). The eosinophil count did not affect the risk of AECOPD or forced expiratory volume in 1 second (FEV1) changes according to exposure to inhaled corticosteroid (ICS). However, by increasing the cutoff value for the eosinophil count from 200/µL to 600/µL, the odds ratio for risk of exacerbation increased serially from 0.82 to 2.96 on trend analysis. CONCLUSION: In patients with non-ACOS COPD, the blood eosinophil count and percent were not associated with FEV1 changes, quality of life (QoL), AECOPD frequency, or response to ICS. The clinical implication of the blood eosinophil count should not be overestimated in patients with non-ACOS COPD.