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.

Strategies to Improve Smoking Cessation for Participants in Lung Cancer Screening Program: Analysis of Factors Associated with Smoking Cessation in Korean Lung Cancer Screening Project (K-LUCAS).

PURPOSE: Smoking cessation intervention is one of the key components of successful lung cancer screening program. We investigated the effectiveness and related factors of smoking cessation services provided to the participants in a population-based lung cancer screening trial. MATERIALS AND METHODS: The Korean Lung Cancer Screening Project (K-LUCAS) is a nationwide, multi-center lung cancer screening trial that evaluates the feasibility of implementing population-based lung cancer screening. All 5,144 current smokers who participated in the K-LUCAS received a mandatory smoking cessation counseling. Changes in smoking status were followed up using a telephone survey in 6 months after lung cancer screening participation. The lung cancer screening's impact on smoking cessation is analyzed by variations in the smoking cessation interventions provided in screening units. RESULTS: Among 4,136 survey responders, participant's motivation to quit smoking increased by 9.4% on average after lung cancer screening. After 6 months from the initial screening, 24.3% of participants stopped smoking, and 10.6% of participants had not smoked continuously for at least 6 months after screening. Over 80% of quitters stated that participation in lung cancer screening motivated them to quit smoking. Low-cost public smoking cessation program combined with lung cancer screening increased the abstinence rates. The smokers were three times more likely to quit smoking when the smoking cessation counseling was provided simultaneously with low-dose computed tomography screening results than when provided separately. CONCLUSION: A mandatory smoking cessation intervention integrated with screening result counselling by a physician after participation in lung cancer screening could be effective for increasing smoking cessation attempts.

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.

Comparison of electromagnetic navigation bronchoscopy and transthoracic needle biopsy for diagnosing bronchus sign-positive pulmonary lesions.

OBJECTIVES: Electromagnetic navigation bronchoscopy (ENB) is an advanced technique for diagnosing peripheral pulmonary lesions, and the bronchus sign is a well-established factor for improving the diagnostic performance. However, ENB is a novel technology compared to the commonly adopted transthoracic needle biopsy (TTNB). There are limited data on the comparison of these techniques for diagnosing bronchus sign-positive lesions. Therefore, we aimed to compare the diagnostic yield and complication rates of ENB and TTNB for diagnosing lung cancer in bronchus sign-positive pulmonary lesions. MATERIALS AND METHODS: We assessed 2,258 individuals who underwent either of the techniques for initial biopsy between September 2016 and May 2022 at a tertiary center in South Korea and analyzed 1,248 participants (153 ENB and 1,095 TTNB cases) with a positive bronchus sign. We performed multivariable logistic regression analyses to evaluate the factors associated with the diagnostic yield, sensitivity for malignancy, and procedure-related complications. In addition, the outcomes were compared between the two techniques after a 1:2 propensity score-matching to control for pre-procedural factors. RESULTS: After adjustments for clinical/radiological factors, performing TTNB over ENB was not significantly associated with a higher diagnostic yield but with a higher risk of pneumothorax (OR = 9.69, 95% CI = 4.15-22.59). Propensity score-matching resulted in 459 participants (153 ENB and 306 TTNB cases) with balanced pre-procedural characteristics. The overall diagnostic yield did not differ significantly between ENB and TTNB (85.0% vs. 89.9%, p = 0.124). The diagnostic yield (86.7% vs. 90.3%, p = 0.280) and sensitivity for malignancy (85.3% vs. 88.8%, p = 0.361) were comparable among patients with a class 2 bronchus sign. However, TTNB demonstrated a significantly higher complication rate of pneumothorax (28.8% vs. 3.9%, p < 0.001) and pneumothorax requiring tube drainage (6.5% vs. 2.0%, p = 0.034) than ENB. CONCLUSION: ENB demonstrated a diagnostic yield comparable with that of TTNB for diagnosing bronchus sign-positive peripheral pulmonary lesions with significantly lower complication rates.

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.

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.

Screening for Lung Cancer in Individuals Who Never Smoked: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report.

Screening with low-dose computed tomography of high-risk individuals with a smoking history reduces lung cancer mortality. Current screening guidelines and eligibility criteria can miss more than 50% of lung cancers, and in some geographic areas, such as East Asia, a large proportion of the missed lung cancers are in never-smokers. Although randomized trials revealed the benefits of screening for people who smoke, these trials generally excluded never-smokers. Thus, the feasibility and effectiveness of lung cancer screening of individuals who never smoked are uncertain. Several known and suspected risk factors for lung cancers in never-smokers such as exposure to secondhand smoke, occupational carcinogens, radon, air pollution, and pulmonary diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases, and intrinsic factors, such as age, are well noted. In this regard, knowledge of risk factors may make possible quantification and prediction of lung cancer risk in never smokers. It is worth considering if and how never smokers could be included in population-based screening programs. As the implementation of these programs is challenging in many countries owing to multiple factors and the epidemiologic differences by global regions, these issues will need to be evaluated in each country taking into account various factors, including accuracy of risk assessment and cost-effectiveness of screening in never smokers. This report aims to outline current knowledge on risk factors for lung cancer in never smokers to propose research strategies for this topic and initiate a broader discussion on lung cancer screening of never smokers. Similar considerations can be made in current and ex-smokers, which do not fulfill the current screening inclusion criteria, but otherwise are at increased risk. Although screening of never smokers may in the future be effectively conducted, current evidence to support widespread implementation of this practice is lacking.

Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study.

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. CONCLUSION: The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

The differential prognostic impact of spread through air spaces in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor.

OBJECTIVES: We evaluated the differential prognostic impact of spread through air spaces (STAS) in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor. METHODS: The study population included 506 patients who underwent lobectomy with mediastinal lymph node dissection for pT1b, pT1c, and pT2a adenocarcinoma between 2011 and 2016. We divided the study population into 2 groups according to STAS status, ie, STAS (+) versus STAS (-), and stratified them according to the pT descriptor. A Cox proportional hazard model and inverse probability of treatment weight-adjusted Kaplan-Meier curves were used to evaluate the prognostic impact of STAS on recurrence-free survival (RFS) and its independency in each stratum. RESULTS: Multivariable Cox proportional hazard regression analysis demonstrated that in pT1b and pT1c strata, STAS (+) patients had a 7.02-fold and 2.89-fold greater risk of recurrence than STAS (-) patients, respectively. However, in the pT2a stratum, STAS did not affect RFS. And the RFS of the STAS (+) pT1b/c strata was similar to that of the pT2a stratum. In the pT1b/c strata, inverse probability of treatment weighting-adjusted Kaplan-Meier curves also showed that RFS was significantly worse when STAS was present. Furthermore, the risks for locoregional and distant recurrence were both greater when STAS was present. CONCLUSIONS: The presence of STAS increased the risk of recurrence independently from other poor prognostic factors in patients with pT1b/cN0M0 adenocarcinoma who underwent lobectomy, but not in pT2a patients. The presence of STAS in pT1b/cN0M0 adenocarcinoma was associated with a similar risk of recurrence to that of pT2aN0M0 adenocarcinoma.

Lung Cancer Screening Considerations During Respiratory Infection Outbreaks, Epidemics or Pandemics: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report.

After the results of two large, randomized trials, the global implementation of lung cancer screening is of utmost importance. However, coronavirus disease 2019 infections occurring at heightened levels during the current global pandemic and also other respiratory infections can influence scan interpretation and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections from severe acute respiratory syndrome coronavirus 2 and others, there is also a risk of transmission of these infections to the health care providers, the screenees, and patients. This became evident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to a temporary global stoppage of lung cancer and other cancer screening programs. Data on the optimal management of these situations are not available. The pandemic is still ongoing and further periods of increased respiratory infections will come, in which practical guidance would be helpful. The aims of this report were: (1) to summarize the data available for possible false-positive results owing to respiratory infections; (2) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event; (3) to provide guidance on these situations; and (4) to stimulate research and discussions about these scenarios.

Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma.

Many studies support a stepwise continuum of morphologic changes between atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma (ADC). Here we characterized gene expression patterns and the association of differentially expressed genes and immune tumor microenvironment behaviors in AAH to ADC during ADC development. Tumor tissues from nine patients with ADC and synchronous multiple ground glass nodules/lesions (GGN/Ls) were analyzed using RNA sequencing. Using clustering, we identified genes differentially and sequentially expressed in AAH and ADC compared to normal tissues. Functional enrichment analysis using gene ontology terms was performed, and the fraction of immune cell types was estimated. We identified up-regulated genes (ACSL5 and SERINC2) with a stepwise change of expression from AAH to ADC and validated those expressions by quantitative PCR and immunohistochemistry. The immune cell profiles revealed increased B cell activities and decreased natural killer cell activities in AAH and ADC. A stepwise change of differential expression during ADC development revealed potential effects on immune function in synchronous precursors and in tumor lesions in patients with lung cancer.

Application of N Descriptors Proposed by the International Association for the Study of Lung Cancer in Clinical Staging.

Background Patients with N1 or N2 non-small cell lung cancer exhibit prognostic heterogeneity. To refine the current N staging system, new N stages were proposed by the International Association for the Study of Lung Cancer. However, those proposed new N stages have not been validated. Purpose To evaluate the prognostic performance of the proposed N descriptors for clinical staging. Materials and Methods Participants with non-small cell lung cancer without distant metastasis from January 2010 to December 2014 were retrospectively included. Each patient's clinical N (cN) stage was assigned to one of seven categories (cN0, cN1a, cN1b, cN2a1, cN2a2, cN2b, cN3). The 5-year overall survival rates were estimated with the Kaplan-Meier method. The adjusted hazard ratios (HRs) and their 95% CIs were estimated by using a multivariable Cox proportional hazard model. Ad hoc analyses according to lymph node (LN) size were performed. Results A total of 1271 patients (median age, 66 years; interquartile range, 59-73 years; 812 men) were included. The 5-year overall survival rates were 77.3%, 53.7%, 36.0%, 29.2%, 34.4%, 18.0%, and 12.4% for stages cN0, cN1a, cN1b, cN2a1, cN2a2, cN2b, and cN3, respectively. Patients with cN2b disease had a worse prognosis than patients with cN2a disease (HR, 1.53; 95% CI: 1.06, 2.22; P = .02). There was no prognostic difference between cN1b and cN1a (HR, 1.13; 95% CI: 0.61, 2.09; P = .71); however, there was a difference between cN1 subgroups when stratified by LN size (≥2 cm; HR, 2.26; 95% CI: 1.16, 4.44; P = .02). Within cN2a disease, there were no differences between cN2a1 and cN2a2 (HR, 0.98; 95% CI: 0.61, 1.56; P = .93) or between subgroups according to LN size (HR, 0.74; 95% CI: 0.40, 1.37; P = .34). Conclusion A survival difference was observed between single- and multistation involvement among cN2 disease. The number of involved lymph node stations in patients with cN1 disease and the presence of skip metastasis in patients with cN2 disease were not associated with survival differences. © RSNA, 2021 Online supplemental material is available for this article.

The relationship between the severity of pulmonary fibrosis and the lung cancer stage.

Background: The incidence of idiopathic pulmonary fibrosis (IPF) and mortality related to the disease have steadily increased in recent years. The risk of cancer is approximately eight times higher in IPF patients than in the general population. The purpose of this study is to determine whether the severity of IPF is related to the time interval between IPF diagnosis and lung cancer diagnosis and to the stage of lung cancer at diagnosis. Methods: In this retrospective cohort study, we reviewed the medical records of patients with lung cancer after IPF diagnosis from two tertiary hospitals in South Korea between 2003 and 2018. We identified 61 patients diagnosed with lung cancer at least 3 months after being diagnosed with IPF. Results: The included patients had a mean age of 71.0 years, and all but one were men (98.4%). The interval between IPF diagnosis and lung cancer diagnosis was not related to the gender-age-physiology (GAP) stage (p=0.662). However, in cox proportional hazard models, a higher GAP stage was significantly correlated with an advanced lung cancer stage (odds ratio 11.1, p=0.003). Conclusions: The lung cancer stage at diagnosis was higher in patients with a higher GAP stage than in those with a lower GAP stage. Physicians should consider implementing more frequent surveillance with computed tomography scans for patients with advanced IPF.

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.