Myeloid-derived suppressor cells in pleural effusion as a diagnostic marker for early discrimination of pulmonary tuberculosis from pneumonia.

Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE. Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples. Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE. Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Electromagnetic Navigation Bronchoscopy Versus Radial Endobronchial Ultrasound for Diagnosing Lung Cancer: A Propensity Score-Matched Analysis.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) and radial endobronchial ultrasound (R-EBUS) are advanced imaging-guided bronchoscopy techniques for diagnosing pulmonary lesions. This study aimed to determine the comparative diagnostic yield of sole ENB and R-EBUS under moderate sedation. METHODS: We investigated 288 patients who underwent sole ENB (n=157) or sole R-EBUS (n=131) under moderate sedation for pulmonary lesion biopsy between January 2017 and April 2022. After a 1:1 propensity score-matching to control for pre-procedural factors, the diagnostic yield, sensitivity for malignancy, and procedure-related complications between both techniques were compared. RESULTS: The matching resulted in 105 pairs/procedure for analyses with balanced clinical and radiological characteristics. The overall diagnostic yield was significantly higher for ENB than for R-EBUS (83.8% vs. 70.5%, p=0.021). ENB demonstrated a significantly higher diagnostic yield than R-EBUS among those with lesions>20mm in size (85.2% vs. 72.3%, p=0.034), radiologically solid lesions (86.7% vs. 72.7%, p=0.015), and lesions with a class 2 bronchus sign (91.2% vs. 72.3%, p=0.002), respectively. The sensitivity for malignancy was also higher for ENB than for R-EBUS (81.3% vs. 55.1%, p<0.001). After adjusting for clinical/radiological factors in the unmatched cohort, using ENB over R-EBUS was significantly associated with a higher diagnostic yield (odd ratio=3.45, 95% confidence interval=1.75-6.82). Complication rates for pneumothorax did not significantly differ between ENB and R-EBUS. CONCLUSION: ENB demonstrated a higher diagnostic yield than R-EBUS under moderate sedation for diagnosing pulmonary lesions, with similar and generally low complication rates. Our data indicate the superiority of ENB over R-EBUS in a least-invasive setting.

Correlation of monocyte counts with clinical outcomes in idiopathic nonspecific interstitial pneumonia.

Higher blood monocyte counts are related to worse survival in idiopathic pulmonary fibrosis. However, studies evaluating the association between blood monocyte counts and clinical outcomes of idiopathic nonspecific interstitial pneumonia (iNSIP) are lacking. We evaluated the impact of monocyte counts on iNSIP prognosis. iNSIP patients (n = 126; median age, 60 years; female, n = 64 [50.8%]) diagnosed by surgical lung biopsy were enrolled and categorized into low (monocyte < 600/µL) and high (monocyte ≥ 600/µL) monocyte groups. The median follow-up duration was 53.0 months. After adjusting for age, sex, and smoking history, the annual decline in forced vital capacity (FVC) showed differences between the monocyte groups (Pinteraction = 0.006) (low vs. high; - 28.49 mL/year vs. - 65.76 mL/year). The high-monocyte group showed a worse survival rate (P = 0.01) compared to low monocyte group. The 5-year survival rates were 83% and 72% in the low- and high-monocyte groups, respectively. In the Cox-proportional hazard analysis, older age, male sex, low baseline FVC, and diffusing capacity of the lung for carbon monoxide were independent risk factors for mortality. However, monocyte count (Hazard ratio 1.61, P = 0.126) was not an independent prognostic factor. Although high monocyte count might be associated with faster lung function decline, it could not independently predict survival in iNSIP.

Interstitial pneumonitis associated with dasatinib treatment for chronic myeloid leukemia or acute lymphoblastic leukemia: case series and a literature review.

Dasatinib, a tyrosine kinase inhibitor, is usually prescribed for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, some patients may develop an intolerance to this drug over the years. Among various toxicities related to dasatinib, dasatinib-associated interstitial pneumonitis is not reported frequently in the literature yet. Moreover, published studies have reported only few cases of dasatinib-associated pneumonitis, almost exclusively in chronic myeloid leukemia. In this study, we describe three cases of dasatinib-associated interstitial pneumonitis in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia (a 56-year-old man, a 34-year-old man, and a 46-year-old woman) at our institution. In all three patients, the time from the initiation of dasatinib therapy to the onset of interstitial pneumonitis varied greatly. Among them, one patient underwent a surgical lung biopsy, which revealed chronic granulomatous inflammation without any causative pathogen. In all patients, dasatinib was discontinued after the diagnosis of interstitial pneumonitis, and two patients were treated with systemic steroids. Although infrequent, dasatinib-induced pneumonitis should be considered a possible diagnosis in dasatinib-treated patients with fever and respiratory symptoms. In addition, hematologists and pulmonologists should be aware of this rare but critical toxicity.

Impact of body weight change on clinical outcomes in patients with idiopathic pulmonary fibrosis receiving pirfenidone.

There have been limited studies on the association between prognosis and body weight change in patients with idiopathic pulmonary fibrosis (IPF). This single-center retrospective observational study evaluated the impact of weight loss on outcomes in Korean patients with IPF receiving pirfenidone at a tertiary medical institution. We analyzed 215 IPF patients prescribed pirfenidone from January 1st, 2015 to December 31st, 2019. The patients were categorized into maintained weight (MW; weight gain or loss < 5%/year) and reduced weight (RW; weight loss ≥ 5%/year) groups. The mean age was 71.8 years and 175 (81.4%) were male. There were 54 (25.1%) patients in the RW group. All patients showed a decrease in body weight (baseline vs. after 1 year; 64.1 kg vs. 62.8 kg, P < 0.001). Although baseline lung function showed a difference, there was no difference in the rate of change (forced vital capacity [% of predicted]; P = 0.221, diffusing capacity of the lung for carbon monoxide [% of predicted]; P = 0.973). The MW group had a lower risk of all-cause mortality (P < 0.001). Weight loss appeared to be a significant risk factor for mortality in patients with IPF. Not only disease control with antifibrotic agents, but also efforts to prevent weight loss may be necessary.

The significance of elevated tumor markers among patients with interstitial lung diseases.

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.

Evaluation of the synergistic impact of needle and forceps biopsy with electromagnetic navigation bronchoscopy: the CONFIDENT-ENB trial design.

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.

Impact of Preoperative Diagnostic Biopsy Procedure on Spread Through Airspaces and Related Outcomes in Resected Stage I Non-Small Cell Lung Cancer.

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.

Utility and safety of sole electromagnetic navigation bronchoscopy under moderate sedation for lung cancer diagnosis.

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.

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. METHODS: We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. RESULTS: Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1-82) months. The median age was 55 (range, 33-75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. CONCLUSIONS: The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.

Acute Respiratory Deterioration in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Single-Center Study.

BACKGROUND: Interstitial lung disease (ILD) is associated with increased morbidity and mortality in rheumatoid arthritis (RA). Moreover, acute exacerbation (AE) is a devastating complication of RA plus ILD. However, few data on AE in RA-associated ILD are available. RESEARCH QUESTION: What are the incidence, risk factors, and outcomes of AE in patients with RA-associated ILD? STUDY DESIGN AND METHODS: The clinical data of 310 patients with RA-associated ILD were analyzed retrospectively. AE was defined as the acute worsening of dyspnea typically within 30 days with new bilateral lung infiltration, which was based on a 2016 report by an international working group. RESULTS: The mean age of the participants was 61.9 years, and 56.2% of them were women. During follow-up (median, 47.7 months), AE occurred in 87 patients (28.1%). The 1-year, 3-year, and 5-year cumulative incidence rates of AE in patients with RA-associated ILD were 9.2%, 19.8%, and 29.4%, respectively. Ever smoker status, lower FVC, and shorter 6-min walk distance were significant risk factors for the occurrence of AE. In the multivariate Cox analysis adjusted by age, sex, smoking status, lung function, exercise capacity, and high-resolution CT scan pattern, AE was a significant prognostic factor for overall survival (hazard ratio, 2.423; 95% CI, 1.605-3.660; P < .001) in patients with RA-associated ILD. The 30-day and 90-day mortalities after AE were 12.6% and 29.9%, respectively. INTERPRETATION: Our findings suggest that approximately one-third of patients with RA-associated ILD experience AE and that ever smoker status, and lower lung function and exercise capacity predispose patients to AE. AE significantly affects the overall survival of patients with RA-associated ILD.

Diagnostic and prognostic implications of 2018 guideline for the diagnosis of idiopathic pulmonary fibrosis in clinical practice.

The purpose of this study was to evaluate the implications of the 2018 updated guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) in clinical practice compared to 2011 guideline. This study involved 535 patients including 339 IPF and 196 non-IPF, and we retrospectively evaluated CT classifications of usual interstitial pneumonia (UIP) by two guidelines. Interobserver agreement of 2018 criteria showed moderate reliability (κ = 0.53) comparable to 2011 (κ = 0.56) but interobserver agreement for probable UIP was fair (κ = 0.40). CT pattern of indeterminate for UIP was associated with better prognosis compared with the other groups (adjusted hazard ratio [HR] = 0.36, p < 0.001). Compared to possible UIP, probable UIP demonstrated a lower positive predictive value (PPV, 62.9% vs 65.8%). In analysis of patients with CT patterns of non-definite UIP, diagnosing IPF when CT pattern showed probable UIP with lymphocyte count ≤ 15% in BAL fluid, and either male sex or age ≥ 60 years showed a high specificity of 90.6% and a PPV of 80.8% in the validation cohort. The 2018 criteria provide better prognostic stratification than the 2011 in patients with possible UIP. BAL fluid analysis can improve the diagnostic certainty for IPF diagnosis in patients with probable UIP CT pattern.

Lung cancer probability and clinical outcomes of baseline and new subsolid nodules detected on low-dose CT screening.

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.

Relationship among genetic polymorphism of SLCO1B1, rifampicin exposure and clinical outcomes in patients with active pulmonary tuberculosis.

AIMS: Rifampicin is a key drug for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampicin pharmacokinetics and genetic polymorphisms in the Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampicin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB. METHODS: From February 2016 to December 2019, patients with active pulmonary TB who were taking rifampicin for >1 week were prospectively enrolled. Serial or 1-time blood sampling was conducted to determine rifampicin concentrations. The genotype of 4 single nucleotide polymorphisms of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to acid-fast bacteria culture conversion, chest radiograph score changes from baseline, and all-cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored. RESULTS: A total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampicin clearance or exposure. As the rifampicin exposure increased, the chest radiographs improved significantly, but the duration of acid-fast bacteria culture conversion was not related to the drug exposure. CONCLUSION: SLCO1B1 gene polymorphisms did not influence rifampicin concentrations and clinical outcomes in Korean patients with active pulmonary TB.

Differences in detection patterns, characteristics, and outcomes of central and peripheral lung cancers in low-dose computed tomography screening.

BACKGROUND: Although low-dose computed tomography (LDCT) screening is known to be effective for the detection of lung cancers localized in peripheral lung regions at a curable stage, limited data is available regarding the characteristics and outcomes of central lung cancers diagnosed in a screening cohort. This study aimed to determine whether LDCT screening could effectively detect central lung cancers at an early stage and offer survival benefits. METHODS: We analyzed 52,615 adults who underwent lung cancer screening with LDCT between May 2003 and Dec 2019 at a tertiary center in South Korea. Characteristics and outcomes of those diagnosed with lung cancer, stratified by screen-detection status and cancer location, were evaluated. RESULTS: A total of 352 individuals (281 screen-detected, 71 non-screen-detected) were diagnosed with lung cancer. Compared to screen-detected cancers, non-screen-detected cancers tended to be centrally-located (11.4% vs. 64.8%, P<0.001). Most non-screen-detected central cancers (89.1%) had a negative result on prior LDCT screening. Multivariable regression analyses revealed that for peripheral cancers, screen-detection was associated with a significantly lower probability of diagnosis at an advanced stage [III/IV, odds ratio (OR) =0.15, 95% confidence interval (CI): 0.05-0.45] and mortality [hazard ratio (HR) =0.33, 95% CI: 0.13-0.84]; however, the association was insignificant for central cancers. For screen-detected cancers, central location, compared to peripheral location, was significantly associated with a higher risk of diagnosis at an advanced stage (OR =20.83, 95% CI: 6.67-64.98) and mortality (HR =4.98, 95% CI: 2.26-10.97). CONCLUSIONS: Unlike for peripheral cancers, LDCT screening did not demonstrate an improvement in outcomes of central lung cancers, indicating an important limitation of LDCT screening and the need for developing novel modalities to screen and treat central lung cancer.

Computed tomography patterns predict clinical course of idiopathic pulmonary fibrosis.

BACKGROUND: A new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF. METHODS: Clinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria. RESULTS: The median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335-0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group. CONCLUSIONS: Our results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.

Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers.

BACKGROUND: Although 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. METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: LDCT 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.

KMBARC registry: protocol for a multicentre observational cohort study on non-cystic fibrosis bronchiectasis in Korea.

INTRODUCTION: Despite the significant disease burden of bronchiectasis in Korea, no large-scale, representative prospective cohort studies have been conducted to evaluate the clinical characteristics of Korean patients with bronchiectasis, indicating an urgent need for cohort studies on bronchiectasis. METHODS AND ANALYSIS: The Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) is a prospective, non-interventional observational cohort study on bronchiectasis in Korea. The inclusion criteria of this registry are as follows: (1) adult patients (aged ≥18 years) with or without respiratory symptoms (cough, chronic sputum and/or recurrent respiratory infection) and chest computed tomography revealing bronchiectasis affecting one or more lobes and (2) stable status at the time of registration: patients with bronchiectasis who were admitted for a respiratory aetiology can be enrolled at least 4 weeks after hospital discharge. The exclusion criteria are as follows: (1) bronchiectasis due to cystic fibrosis; (2) traction bronchiectasis associated with interstitial lung disease; (3) patients actively being treated for pneumonia, pulmonary tuberculosis or non-tuberculous mycobacterial infection; (4) patients who are unable or unwilling to provide informed consent; and (5) pregnant patients. Although the KMBARC questionnaires for baseline and annual follow-up data are similar to the European Multicentre Bronchiectasis Audit and Research Collaboration questionnaires, KMBARC has distinctive features such as use of Bronchiectasis Health Questionnaires, measurement with fatigue and depression scales, blood tests, use of consensus definition of exacerbations and information on emergency room or hospitalisation.We aim to recruit at least 1200 patients over the study period from more than 26 hospitals in South Korea. Patients will undergo a detailed baseline and yearly assessment for up to 5 years. The study objectives of the KMBARC registry are as follows: (1) uncovering the natural course of bronchiectasis; (2) aiding in establishing evidence-based bronchiectasis guidelines in Korea; and (3) encouraging and facilitating studies on bronchiectasis in Korea. ETHICS AND DISSEMINATION: This study received necessary approval from the Institutional Review Boards of all participating institutions. The Asan Medical Center Institutional Review Board gave overall approval for the study. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: KCT0003088.

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor.

BACKGROUND: We investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT) chemotherapy in patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. METHODS: Using clinical research data from the Asan Medical Center, we retrospectively analyzed data of patients diagnosed with LMC, confirmed via cerebrospinal fluid (CSF) analysis from January 2008 to December 2017. RESULTS: We identified 1189 patients with lung adenocarcinoma harboring EGFR mutations. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8-23.6) months from the initial lung cancer diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastasis to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. Median survival duration from LMC diagnosis was 3.8 (IQR 1.5-8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of Ommaya reservoir (HR 0.445, P = 0.005) were associated with longer survival. EGFR-tyrosine kinase inhibitor (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion. CONCLUSIONS: Younger age, initial diagnosis of metastatic disease, and metastasis to the brain or different lobes were associated with LMC in patients with EGFR-mutant lung adenocarcinoma. Therapeutic interventions including EGFR-TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes. KEY POINTS: Age and disease status were associated with LMC in patients with EGFR-mutant adenocarcinoma, and EGFR-TKI, Ommaya reservoir, and good performance status were related to survival benefit.