Abstract Background Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. Methods We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. Results The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038–0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. Conclusions Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

BACKGROUND:Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. METHODS:We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. RESULTS:While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003-2005 to 468 in 2018-2020, that of other institutions increased from 0 to 238. The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%. The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, rs = -0.740, P = 0.003) and recent administrative difficulties were encountered (rs = -0.616, P = 0.019). CONCLUSION:This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset ( n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

BACKGROUND: Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC).RESEARCH QUESTION: Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC?STUDY DESIGN AND METHODS: For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endo-scopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021).RESULTS: The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with >= 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS -M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration. INTERPRETATION: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC.

BACKGROUND:There is little information on the optimal storage conditions for recovery of nontuberculous Mycobacterium spp. (NTM) from refrigerated sputum.OBJECTIVES:We investigated the storage duration that could increase the culture-positive rate of NTM isolates.DESIGN:In this prospective study, we collected NTM isolates and clinical data from patients with repeated culture-positive NTM pulmonary disease (NTM-PD).METHODS:From June 2020 to July 2021, the participants were instructed to randomly collect six sputum samples and immediately store them in a refrigerator at 4°C until the date of their clinic visit. At the outpatient visits, expectorated spot sputum samples were collected.RESULTS:A total of 226 sputum samples were collected from 35 patients. The median duration of refrigeration was 6 days (maximum duration: 36 days). The overall culture-positive rate was 81.6%. While there was a trend for a higher culture positivity rate when stored for ⩽3 weeks, this was not significant compared with those stored for >3 weeks (p = 0.610). According to sputum microscopy, smear-positive sputum was 100% isolated, but smear-negative samples had a culture-positive rate of 77.5%. Similarly, there was no significant association between sputum storage duration and culture positivity (p = 0.511). In addition, the recovery rate of the refrigerated sputum was comparable with the collected spot expectorated sputum (82.6% versus 80.6%, p = 0.795), which is suggestive of the long-term viability of NTM in refrigerated sputum.CONCLUSION:Our data demonstrated the long-term viability of refrigerated NTM, and the culture positivity rate of these samples was comparable with the spot expectorated sputum. These results suggest that implementing sputum refrigeration would enhance convenience in diagnosing and following patients with NTM-PD.PLAIN LANGUAGE SUMMARY:Easy way to diagnose NTM lung diseasesUnder usual circumstances, most patients with suspected NTM submit spontaneously expectorated sputum rather than induced sputum for the purpose of testing the causative organism. By collecting and storing sputum specimens for a longer period than before, it is expected that more sufficient and adequate collection of sputum specimens will be possible.

BACKGROUND: Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC? STUDY DESIGN AND METHODS: We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses. RESULTS: STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity. INTERPRETATION: Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS.

Background Enteral nutrition (EN) supply within 48 hours after intensive care unit (ICU) admission improves clinical outcomes. The “new ICU evaluation & development of nutritional support protocol (NICE-NST)” was introduced in an ICU of tertiary academic hospital. This study showed that early EN through protocolized nutritional support would supply more nutrition to improve clinical outcomes. Methods This study screened 170 patients and 62 patients were finally enrolled; patients who were supplied nutrition without the protocol were classified as the control group (n=40), while those who were supplied according to the protocol were classified as the test group (n=22). Results In the test group, EN started significantly earlier (3.7±0.4 days vs. 2.4±0.5 days, P=0.010). EN calorie (4.0±1.0 kcal/kg vs. 6.7±0.9 kcal/kg, P=0.006) and protein (0.17±0.04 g/kg vs. 0.32±0.04 g/kg, P=0.002) supplied were significantly higher in the test group. Although EN was supplied through continuous feeding in the test group, there was no difference in complications such as feeding hold due to excessive gastric residual volume or vomit, and hyper- or hypo-glycemia between the two groups. Hospital mortality was significantly lower in the group that started EN within 1.5 days (42.9% vs. 11.8%, P=0.018). The proportion of patients who started EN within 1.5 days was higher in the test group (40.9% vs. 17.5%, P=0.044). Conclusions The NICE-NST may improve EN supply and mortality of critically ill patients without increasing complications.

Background Electromagnetic navigation bronchoscopy (ENB) is an emerging advanced imaging-guided bronchoscopy technique for diagnosing peripheral lung lesions. However, the selection strategy for the optimal biopsy device and whether adopting a multi-tool strategy increases the diagnostic yield remains undetermined. The CONFIDENT-ENB trial (NCT05110131) is a prospective randomized study on ENB, performed in a least-invasive setting. The primary aim is to evaluate whether a combination of needle aspiration and forceps biopsy improves the diagnostic performance, and assess the comparative diagnostic value and discordance of the two devices. Methods The trial will recruit 142 participants with lung lesions suspected of malignancy who are eligible for an elective ENB procedure under moderate sedation. Participants will undergo ENB-guided needle aspiration and forceps biopsy in a randomized order without the use of any complementary techniques. All participants will be followed up subsequently for up to 12 months to conclude the final diagnosis of the biopsied lesions. Primary outcomes include the diagnostic yield and sensitivity of each biopsy modality and the diagnostic yield of the combined modalities. Discussion The CONFIDENT-ENB trial will prospectively evaluate the synergistic effectiveness and comparative accuracy of ENB-guided needle aspiration and forceps biopsy in a least-invasive setting. The results are expected to improve our understanding of the optimal tool-selection strategy for ENB. Trial registration : ClinicalTrials.gov (NCT05110131). Prospectively registered on 5 November 2021.

Background: Electromagnetic navigation bronchoscopy (ENB) is an emerging technique for diagnosing pulmonary lesions. However, limited data is available on its sole utility under a least invasive setting without general anesthesia. We aimed to evaluate the diagnostic performance and safety of sole ENB under moderate sedation for diagnosing pulmonary lesions suspicious for lung cancer and to determine clinical factors associated with a better diagnostic yield. Methods: We performed a retrospective analysis of consecutive patients who underwent sole ENB under moderate sedation for lung lesion biopsy between August 2016 and June 2021 at Seoul National University Bundang Hospital, a tertiary center in South Korea. Diagnostic yield of the ENB-guided biopsy, safety endpoints defined by the incidence and severity of associated complications, and factors associated with higher diagnostic yield were evaluated. Results: A total of 94 patients were evaluated. The final diagnostic yield of ENB was 81.5% (75/92), excluding two indeterminate cases. The diagnostic yield ranged from 79.8% to 81.9% assuming all indeterminate cases were false-negatives (79.8%) and true-negatives (81.9%). The sensitivity and specificity for malignancy were 77.6% (ranging from 75.6% to 77.6%) and 100%, respectively. Any-grade pneumothorax occurred in 4.3% of the patients, and 2.1% developed pneumothorax requiring additional intervention. Multivariable analyses identified the presence of a class 2 bronchus sign as the only significant predictor for a higher diagnostic yield (odds ratio =4.83, 95% CI: 1.16-20.12). The diagnostic yield of ENB among those with class 2 bronchus sign was 89.8% (53/59). Conclusions: Sole ENB under moderate sedation for diagnosing pulmonary lesions displayed a good diagnostic yield and safety profile, thus confirming its utility in a least-invasive setting. Moreover, sole ENB could be possibly be superior to transthoracic needle aspiration for diagnosing lesions with class 2 bronchus sign accounting for similar yields and lower complication rates.

Purpose The importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the "well-dying law" in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU. Methods The Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed. Results After the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis. Conclusion Our study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved.

Background/Aims: Current evidence supports lung ultrasound as a point-of-care alternative diagnostic tool for various respiratory diseases. We sought to determine the utility of lung ultrasound for early detection of pneumonia and for assessment of respiratory failure among patients with coronavirus disease 2019 (COVID-19). Methods: Six patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction were enrolled. All had undergone chest X-ray and chest computed tomography (CT) on the day of admission and underwent multiple point-of-care lung ultrasound scans over the course of their hospitalization. Results: Lung ultrasound detected early abnormal findings of representative B-lines in a patient with a normal chest X-ray, corresponding to ground-glass opacities on the chest CT scan. The ultrasound findings improved as her clinical condition improved and her viral load decreased. In another minimally symptomatic patient without significant chest X-ray findings, the ultrasound showed B-lines, an early sign of pneumonia before abnormalities were detected on the chest CT scan. In two critically ill patients, ultrasound was performed to assess for evaluation of disease severity. In both patients, the clinicians conducted emergency rapid sequence intubation based on the ultrasound findings without awaiting the laboratory results and radiological reports. In two children, ultrasound was used to assess the improvement in their pneumonia, thus avoiding further imaging tests such as chest CT. Conclusions: Lung ultrasound is feasible and useful as a rapid, sensitive, and affordable point-of-care screening tool to detect pneumonia and assess the severity of respiratory failure in patients hospitalized with COVID-19.

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271–4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.

Background The purpose of a rapid response system (RRS) is to reduce the incidence of preventable cardiopulmonary arrests (CPAs) and patient deterioration in general wards. The objective of this study is to investigate the incidence and temporal trends of preventable CPAs and determine factors associated with preventable CPAs in a hospital with a mature RRS. Methods This was a single-center prospective cohort study of all CPAs occurring in the general ward between March 2017 and June 2020. The RRS operates from 07:00 to 23:00 on weekdays and from 07:00 to 12:00 on Saturdays. All CPAs were reviewed upon biweekly conference, and a panel of intensivists judged their preventability. Trends of preventable CPAs were analyzed using Poisson regression models and factors associated with preventable CPAs were analyzed using multivariable logistic regression. Results There were 253 CPAs over 40 months, and 64 (25.3%) of these were preventable. The incidence rate of CPAs was 1.07 per 1000 admissions and that of preventable CPAs was 0.27 per 1000 admissions. The number of preventable CPAs decreased by 24% each year (incidence rate ratio = 0.76; p = 0.039) without a change in the total CPA incidence. The most common contributor to the preventability was delayed response from physicians (n = 41, 64.1%). A predictable CPA with a pre-alarm sign had increased odds in the occurrence of preventable CPAs, while a cardiac cause of CPAs and RRS operating hours had decreased odds in terms of occurrence of preventable CPA. Conclusion Our study showed that one-fourth of all CPAs occurring in the general wards were preventable, and these arrests decreased each year. A mature RRS can evolve to reduce preventable CPAs with regular self-evaluation. Efforts should be directed at improving physicians’ response time since a delay in their response was the most common cause of preventable CPAs.

Background/Aims Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF. Methods This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). Results The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was −6.56% (95% confidence interval [CI], −9.26 to −3.87) per year before, but −4.43% (95% CI, −5.87 to −3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was −4.96% (95% CI, −6.82 to −3.09) per year before, but −1.79% (95% CI, −2.75 to −0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II–III than in the stage I group. Conclusions The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

The incidence of pulmonary nontuberculous mycobacterial (NTM) infection is high in patients with underlying lung disease such as bronchiectasis. Although previous studies have reported many risk factors contributing to the development of NTM-lung disease (LD), only a few reports on the relationship of the characteristics of patients, such as body mass index (BMI), skeletal mass, and fat mass, with NTM-LD have been published. We aimed to investigate the association between these parameters and NTM-LD in patients with bronchiectasis. A monocentric retrospective study in a university hospital was conducted over 4 years (2013-2016). Parameters including BMI, skeletal mass, and fat mass were measured using bioelectrical impedance analysis in noncystic fibrosis bronchiectasis patients. Patients were grouped by the presence or absence of NTM-LD, and the differences in BMI, skeletal mass, and fat mass between the 2 groups were compared. In the NTM-LD group, the progression of disease was also followed. Two hundred forty-five patients with bronchiectasis were enrolled in the study. One hundred six subjects (48%) had NTM-LD. These patients with NTM-LD were predominantly female, and had a significantly lower body weight (58.20 +/- 8.84 vs 54.16 +/- 8.99, P < .001), BMI (22.67 +/- 3.04 vs 21.20 +/- 2.59 kg/m(2), P < .001), fat mass (16.19 +/- 6.60 vs 14.23 +/- 5.79, P = .013), and fat mass index (FMI; 6.79 +/- 2.70 vs 5.57 +/- 2.27 kg/m(2), P < .001). Multivariate regression analysis showed that both female sex and lower FMI but not skeletal muscle index were independent risk factors for NTM-LD after adjusting for age, bronchiectasis severity index, and BMI (odds ratio 3.86 (1.99-7.78); 0.72 (0.63-0.82), P < .001, respectively). Our results suggest that lower FMI may contribute to susceptibility to NTM infection in patients with bronchiectasis, independent of age or its severity.

Background The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive. Methods To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR). Results We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10 −7 ), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10 −8 . The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A , a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (β, −4.627; 95% CI, −8.768 to −0.486; p=0.029). Conclusions The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A .

Proton pump inhibitors (PPIs), followed by histamine 2 receptor antagonists (H2RAs), are the most commonly used drugs to prevent gastrointestinal bleeding in critically ill patients through stress ulcer prophylaxis. The relative efficacy and drug-related adverse events of PPIs and H2RAs remain unclear. In this retrospective, observational, comparative cohort study, PPIs and H2RAs for stress ulcer prophylaxis in critically ill patients were compared using a common data model. After propensity matching, 935 patients from each treatment group (PPI or H2RA) were selected. The PPI group had a significantly higher 90-day mortality than the H2RA group (relative risk: 1.28; P = 0.01). However, no significant inter-group differences in the risk of clinically important gastrointestinal bleeding were observed. Moreover, there were no significant differences between the groups concerning the risk of pneumonia or Clostridioides difficile infection, which are known potential adverse events related to these drugs. Subgroup analysis of patients with high disease severity were consistent with those of the total propensity score-matched population. These findings do not support the current recommendations, which prefer PPIs for gastrointestinal bleeding prophylaxis in the intensive care unit.

BackgroundAlthough lung cancer screening using low-dose computed tomography (LDCT) is now widely used in clinical practice, the characteristics and outcomes of diagnostic procedures related to screen-detected nodules in never-smokers remain unclear. We aimed to determine the incidence of nodules considered for invasive biopsy and evaluate the final diagnoses and procedure-related complications in never-smokers in comparison to ever-smokers who underwent LDCT screening.MethodsWe evaluated 37 436 asymptomatic adults (17 968 never-smokers and 19 468 ever-smokers) who underwent LDCT screening for lung cancer between January 2009 and December 2018 at a tertiary centre in South Korea. The rates of invasive diagnostic procedures for detected nodules and related complications, and the diagnostic outcomes were determined in the never-smoker and ever-smoker groups.ResultsAmong the never-smokers, 2908 (16.2%) out of 17 968 had positive nodules. Overall, 139 (0.77%) out of 17 968 never-smokers and 194 (1.00%) out of 19 468 ever-smokers underwent invasive biopsy (p=0.022). Lung cancer was diagnosed in 84 (0.47%) out of 17 968 never-smokers and 123 (0.63%) out of 19 468 ever-smokers (p=0.032). The proportions of participants diagnosed with benign disease after invasive biopsy (false-positive) were 50 (0.28%) out of 17 968 and 69 (0.35%) out of 19 468 in the never-smoker and ever-smoker groups, respectively (p=0.191). Multivariate analyses revealed no significant associations of smoking with the risk of a false-positive diagnosis (OR 0.98, 95% CI 0.62–1.57) and complications (OR 1.33, 95% CI 0.65–3.73) after biopsy. Of the 84 never-smokers with lung cancer, 82 (97.6%) had adenocarcinoma, and 75 (89.3%) were in stage I with a favourable prognosis.ConclusionsLDCT screening in never-smokers resulted in a notable detection rate of lung nodules, which warranted invasive biopsy. The lung cancer detection rate was lower in never-smokers than in ever-smokers. However, no significant differences in the false-positive and complication rates were observed between the two groups. Accordingly, a more specifically tailored management strategy is needed for screen-detected nodules in Asian never-smokers.

Background Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening. Methods We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined. Results A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81). Conclusions LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.