Predicting Non-Small-Cell Lung Cancer Survival after Curative Surgery via Deep Learning of Diffusion MRI.

BACKGROUND: the objective of this study is to evaluate the predictive power of the survival model using deep learning of diffusion-weighted images (DWI) in patients with non-small-cell lung cancer (NSCLC). METHODS: DWI at b-values of 0, 100, and 700 sec/mm2 (DWI0, DWI100, DWI700) were preoperatively obtained for 100 NSCLC patients who underwent curative surgery (57 men, 43 women; mean age, 62 years). The ADC0-100 (perfusion-sensitive ADC), ADC100-700 (perfusion-insensitive ADC), ADC0-100-700, and demographic features were collected as input data and 5-year survival was collected as output data. Our survival model adopted transfer learning from a pre-trained VGG-16 network, whereby the softmax layer was replaced with the binary classification layer for the prediction of 5-year survival. Three channels of input data were selected in combination out of DWIs and ADC images and their accuracies and AUCs were compared for the best performance during 10-fold cross validation. RESULTS: 66 patients survived, and 34 patients died. The predictive performance was the best in the following combination: DWI0-ADC0-100-ADC0-100-700 (accuracy: 92%; AUC: 0.904). This was followed by DWI0-DWI700-ADC0-100-700, DWI0-DWI100-DWI700, and DWI0-DWI0-DWI0 (accuracy: 91%, 81%, 76%; AUC: 0.889, 0.763, 0.711, respectively). Survival prediction models trained with ADC performed significantly better than the one trained with DWI only (p-values < 0.05). The survival prediction was improved when demographic features were added to the model with only DWIs, but the benefit of clinical information was not prominent when added to the best performing model using both DWI and ADC. CONCLUSIONS: Deep learning may play a role in the survival prediction of lung cancer. The performance of learning can be enhanced by inputting precedented, proven functional parameters of the ADC instead of the original data of DWIs only.

The lung microbiota in nontuberculous mycobacterial pulmonary disease.

BACKGROUND: The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients. METHODS: We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions). RESULTS: Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value. CONCLUSIONS: We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues. TRIAL REGISTRATION: Clinical Trial registration number: NCT00970801.

Prognostic value of pretherapeutic FDG PET/CT in non-small cell lung cancer with pulmonary lymphangitic carcinomatosis.

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.

Impact of interstitial lung abnormalities on postoperative pulmonary complications and survival of lung cancer.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown. RESEARCH QUESTION: This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer. STUDY DESIGN AND METHODS: A matched case-control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage. RESULTS: Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p<0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p<0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p<0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002). CONCLUSIONS: The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival.

Efficacy of Combining Multiple Electromagnetic Navigation Bronchoscopy Modalities for Diagnosing Lung Nodules.

Electromagnetic navigation bronchoscopy (ENB) is one of the non-invasive methods used for lung nodule biopsy. We evaluated the efficacy of combining radial endobronchial ultrasound (R-EBUS)-guided transbronchial lung biopsy (TBLB) with ENB-guided TBLB or transbronchial needle aspiration (TBNA) for diagnosing lung nodules. Forty patients with a lung nodule underwent ENB-TBLB or TBNA, followed by R-EBUS-TBLB if available. The final diagnosis was benign or malignant, depending on the surgical pathology or 24-month follow-up computed tomography (CT). We compared the sensitivity, negative predictive value, and accuracy between combinations of procedures. The mean nodule size was 21.65 mm, and 60.0% of the nodules were solid. The bronchus was within the nodule in 67.5% and 65.0% of cases examined using CT and R-EBUS, respectively. The accuracies of ENB-TBLB alone, ENB-TBLB/TBNA, and R-EBUS-TBLB plus ENB-TBLB/TBNA were 74.4%, 82.5%, and 90.0%, respectively. The sensitivity levels of the aforementioned procedures were 69.8%, 78.8%, and 87.9%, respectively. Among 21 patients who underwent both ENB-TBLB and R-EBUS-TBLB, the latter revealed malignant cells in three of nine patients (33.3%) with benign ENB-TBLB results. Combined ENB-TBLB/TBNA and R-EBUS-TBLB had increased sensitivity and diagnostic accuracy for lung nodules. ENB and R-EBUS are complementary; using both modalities improves the sensitivity and accuracy of lung nodule diagnoses.

Comparison of clinical outcomes of pulmonary sequestration in adults between surgery and non-surgery groups.

Background: Pulmonary sequestration (PS) is a rare congenital lung malformation that can be incidentally diagnosed in adulthood. The natural course of PS in adults is scarcely known. Methods: In this retrospective cohort study, medical records and imaging results of adult patients diagnosed with PS between 1994 and 2019 were reviewed. Diagnoses of PS were confirmed by histopathological findings in resected cases, while non-resected cases were diagnosed based on the presence of anomalous systemic arterial supply and abnormal lung parenchyma on enhanced chest computed tomography (CT). Results: Among 104 patients with PS, the median age at diagnosis was 40.5 years, and 69 (66.3%) patients were asymptomatic. Patients in the surgery group were significantly younger (38.6 vs. 45.3 years, respectively, P=0.016), were more likely to be symptomatic initially (51.6% vs. 28.6%, respectively, P=0.015), and had larger PS (90.0 vs. 66.3 mm, respectively, P<0.001) than the non-surgery group. Of the patients in the surgery group, 29.0% (18/62) experienced postoperative complications. In the surgically resected cases, infections were only detected in intralobar PS, not in extralobar PS. Among 25 subjects without initial symptoms in the non-surgery group, 24 (96.0%) remained asymptomatic at the last follow-up. Conclusions: Adults with PS tended to undergo resection if they were young, symptomatic, and had large PS (a median diameter of 90.0 mm). Almost all subjects who were initially asymptomatic and did not undergo surgery remained asymptomatic at the last follow-up. Therefore, considering the indolent course of PS, initially asymptomatic adults with PS could be followed up without surgery.

Antibiotic Maintenance and Redevelopment of Nontuberculous Mycobacteria Pulmonary Disease after Treatment of Mycobacterium avium Complex Pulmonary Disease.

Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of nontuberculous mycobacteria-pulmonary disease (NTM-PD) after microbiological cure of Mycobacterium avium complex (MAC)-PD. This retrospective study included 631 MAC-PD patients who achieved microbiological cure between 1994 and 2021. Data on the antibiotic maintenance period, defined as the time between culture conversion and treatment completion, were collected. Redevelopment, the subsequent diagnosis of NTM-PD regardless of causative organism after microbiological cure, was investigated. Factors associated with redevelopment were analyzed after adjusting for disease severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) scoring system. In total, 205 (33%) patients experienced redevelopment, with a median maintenance period after culture conversion of 15.0 months (interquartile range, 13.0 to 22.0 months). A greater proportion of patients with the nodular bronchiectatic form of MAC-PD (87% versus 80%, P = 0.033) and a longer maintenance period (median 15.0 versus 14.0 months, P < 0.001) were noted in the redevelopment group compared with the nonredevelopment group. The cumulative rate of redevelopment according to the maintenance period did not differ between the >12-month and ≤12-month groups in the total patient population or the subgroups sorted according to BACES severity. No association between a maintenance period >12 months and redevelopment was identified in multivariate models. Extending the antibiotic maintenance period more than 12 months did not reduce the redevelopment rate even with adjustment for disease severity, suggesting the need to further optimize the duration of the antibiotic maintenance period. IMPORTANCE Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of Mycobacterium avium complex-pulmonary (MAC-PD) disease after microbiological cure. To improve treatment outcomes and reduce the recurrence rate, current guidelines recommend maintenance of antibiotics for a minimum of 12 months after achievement of negative culture conversion. However, the optimal duration of antibiotic therapy for MAC-PD is not currently known. Moreover, in real-world clinical practice, total antibiotic duration is mainly impacted by the length of the maintenance period; however, it is unknown whether extending the maintenance period is beneficial for preventing redevelopment of NTM-PD. Our study may help to address concerns regarding the antibiotic maintenance period after achievement of negative culture conversion in patients with MAC-PD.

The Higher Incidence of COVID-19 in Patients With Non-Tuberculous Mycobacterial Pulmonary Disease: A Single Center Experience in Korea.

The aim of our study was to investigate the incidence of and risk factors for coronavirus disease 2019 (COVID-19) in patients with non-tuberculous mycobacterial-pulmonary disease (NTM-PD). A total of 3,866 patients with NTM-PD were retrospectively identified from a single center. Compared to the general population of Korea, patients with NTM-PD had a substantially increased age-standardized incidence of COVID-19 from January 2020 to February 2021 (2.1% vs. 0.2%). The odds of being infected with COVID-19 was particularly higher in patients who received treatment for NTM-PD than in those who did not receive treatment for NTM-PD (adjusted odd ratio = 1.99, 95% confidence interval = 1.09-3.64, P = 0.026). Patients with NTM-PD might be regarded as a high-risk group for COVID-19 and may need a more proactive preventive strategy for COVID-19 and other pandemics in the future.

Clinical utility of EBUS-TBNA of hilar, interlobar, and lobar lymph nodes in patients with primary lung cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS-TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. METHODS: This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS-TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS-TBNA who did not undergo surgical sampling/clinical follow-up or who received radiotherapy/chemotherapy were excluded. RESULTS: The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS-TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs <10 mm than ≥10 mm in size (90.1% vs. 97.8%; p < 0.001). There was no significant difference in diagnostic performance according to the nodal station (10 vs. 11/12) and left- versus right-sided LNs. The diagnostic sensitivity (100 vs. 95.5%; p = 0.221) and specificity (100 vs. 100%) of N3 LNs was not significantly different from those of N1 LNs. In this study, eight (8/91, 8.8%) patients with cN1 NSCLC received neoadjuvant treatment based on the results of EBUS-TBNA. CONCLUSION: EBUS-TBNA accurately evaluates station 10/11/12 LNs of both N1 and N3 disease. The diagnostic performances of EBUS-TBNA for station 10/11/12 LNs seem to be comparable to those of EBUS-TBNA for mediastinal LNs.

Clinical characteristics and prognostic factors of fibrotic nonspecific interstitial pneumonia.

AIM: Several studies have reported favorable outcomes of nonspecific interstitial pneumonia (NSIP); however, its prognosis and prognostic factors remain unclear. This study aimed to determine the outcomes of fibrotic NSIP and the prognostic factors for progression, relapse, and survival. METHODS: In this retrospective study, we reviewed the clinical data of 204 patients diagnosed with fibrotic NSIP by surgical lung biopsy at Samsung Medical Center. The factors associated with survival and disease progression or relapse were determined using Cox proportional hazard analysis. RESULTS: The median age of patients was 54 years and 67 (33%) patients were male. Also, 47 patients (23%) were current or ex-smokers. In all, 141 (69%) patients were diagnosed with idiopathic NSIP, while 63 (31%) patients were associated with connective tissue diseases. Progression or relapse was observed in 100 (49%) patients. The 5-year and 10-year survival rates were 94.6% and 90.4%, respectively. The factors associated with disease progression and relapse were diffusing capacity for carbon monoxide (DLco) <60% [adjusted hazard ratio (HR), 1.739; 95% confidence interval (CI), 1.036-2.921; p = 0.036], bronchoalveolar lavage (BAL) lymphocyte >15% (adjusted HR, 0.592; 95% CI, 0.352-0.994; p = 0.047), and treatment with corticosteroid and azathioprine (adjusted HR, 0.556; 95% CI, 0.311-0.955; p = 0.048). Disease progression or relapse was associated with mortality (adjusted HR, 7.135; 95% CI, 1.499-33.971; p = 0.014). CONCLUSION: Preserved lung function, BAL lymphocytosis, and treatment with corticosteroids and azathioprine were associated with lower risks of disease progression and relapse, which were risk factors for mortality.

Preoperative Helical Dynamic Enhanced Multidetector Row Computed Tomography: Can It Be a Prognostic Indicator in Early-Stage Non-small Cell Lung Cancer?

OBJECTIVE: This study aimed to investigate the prognostic significance of dynamic contrast-enhanced computed tomography in patients with stage IA non-small cell lung cancer (NSCLC). METHODS: We retrospectively enrolled 139 patients (77 men, 62 women; mean age, 59 years) with stage IA NSCLC who underwent dynamic contrast-enhanced computed tomography. Data on age, pathologic subtype, peak enhancement, and net enhancement of primary lung cancer were collected and correlated with 5-year survival. RESULTS: Peak enhancement had a significant correlation with overall survival in the univariable analysis (hazard ratio [HR], 1.18, confidence interval [CI], 1.01-1.38; P = 0.04) and in the multivariable analysis (HR, 1.19; CI, 1.01-1.39; P = 0.04). Patients with peak enhancement of 90 Hounsfield unit or higher had a significantly increased risk of death compared with patients with less enhancement after curative surgery (HR, 4.15; CI, 1.23-13.95; P = 0.02). CONCLUSIONS: Our study confirmed the prognostic significance of peak enhancement as an indicator for the overall survival of stage IA NSCLC.

Clinical Utility of Plasma Cell-Free DNA EGFR Mutation Analysis in Treatment-Naïve Stage IV Non-Small Cell Lung Cancer Patients.

BACKGROUND: Plasma cell-free Deoxyribo nucleic acid epidermal growth factor receptor (EGFR) mutation tests are widely used at initial diagnosis and at progression in stage IV non-small cell lung cancer (NSCLC). We analyzed the factors associated with plasma EGFR mutation detection and the effect of plasma EGFR genotyping on the clinical outcomes of the patients with treatment-naïve stage IV NSCLC. METHODS: In this retrospective cohort study, we included subjects with treatment-naïve stage IV NSCLC who underwent plasma EGFR genotyping between 2018 and 2020. The presence of plasma EGFR mutation was determined by real-time polymeric chain reaction. RESULTS: The prevalence of EGFR mutation in this cohort was 52.7% (164/311). Among 164 EGFR mutant subjects, 34 (20.7%) were positive for the plasma EGFR mutation assay only. In multivariable analysis, the detection of plasma EGFR mutation was significantly related to higher serum carcinoembryonic antigen levels, never-smoker status, N3 stage, and brain or intrathoracic metastasis. The time to treatment initiation (TTI) of the plasma EGFR mutation-positive group (14 days) was shorter than that of the plasma EGFR mutation-negative group (21 days, p < 0.001). More patients received the 1st line EGFR-TKI in the plasma positive group compared with the tissue positive group. CONCLUSION: Smoking status and the factors reflecting tumor burden were associated with the detection of plasma EGFR mutation. The plasma EGFR mutation assay can shorten the TTI, and facilitate the 1st line EGFR-TKI therapy for patients with treatment-naïve stage IV NSCLC, especially in the region of high-prevalence of EGFR mutation.

Treatment outcomes of Mycobacterium avium complex pulmonary disease according to disease severity.

Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n = 331), moderate (n = 503), and severe (n = 158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (p < 0.001). In patients with mild disease, culture conversion rates were similar between intermittent (84%, 166/198) and daily (87%, 116/133) treatment (p = 0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83-1.41; p = 0.578). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD.

Pulmonary Tuberculosis and the Incidence of Lung Cancer among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Although a history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether a history of PTB affects lung cancer development in patients with COPD. Objectives: To investigate whether a history of PTB is associated with an increased risk of lung cancer development in a population with COPD. Methods: This cohort study included a nationwide representative sample of 13,165 Korean men and women with COPD, aged between 50 and 84 years. In addition, to assess whether the relationship between PTB and lung cancer risk differs between participants with and without COPD, a matched cohort without COPD was included. Participants were matched 1:3 for age, sex, smoking history, and PTB status based on the index health screening examination of corresponding participants with COPD. The two cohorts were followed up for 13 years (January 1, 2003, to December 31, 2015). PTB was diagnosed on the basis of the results of chest radiography, and incident lung cancer was identified from hospitalization and outpatient visit claims (International Classification of Diseases, Tenth Revision diagnosis code C33 or C34). Results: During 370,617 person-years (PY) of follow-up (median follow-up, 7.7 yr) in the COPD group, we observed 430 incident cases of lung cancer in participants without a history of PTB (incidence rate, 524 per 100,000 PY) and 148 cases in those with a history of PTB (incidence rate, 931 per 100,000 PY). Compared with participants without a PTB history, the fully adjusted subdistribution hazard ratio (95% confidence interval [CI]) for lung cancer in those with a history of PTB was 1.24 (1.03-1.50). The association of PTB history and lung cancer development was more evident in never-smokers with COPD. In contrast, among participants without COPD, the corresponding hazard ratio (95% CI) was 0.98 (0.78-1.22). There was no interaction among PTB, smoking status, and COPD. Conclusions: A history of PTB was associated with an increased risk of developing lung cancer among patients with COPD in our country with an intermediate tuberculosis burden. Patients with COPD with a history of PTB, particularly never-smokers, might benefit from periodic screening or assessment for lung cancer development.

The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The role of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ -2 mm), and no change (-2 mm < size change < +2 mm). RESULTS: A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025). CONCLUSION: Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Impact of Time Between Diagnosis and Treatment for Nontuberculous Mycobacterial Pulmonary Disease on Culture Conversion and All-Cause Mortality.

BACKGROUND: Limited data are available regarding when to start treatment after a diagnosis of nontuberculous mycobacteria-pulmonary disease (NTM-PD) or regarding how achieving culture conversion affects NTM-PD outcomes. RESEARCH QUESTION: Does the time between diagnosis and antibiotic initiation influence culture conversion or all-cause mortality in NTM-PD, and is there any association between achieving culture conversion after antibiotics and reduced all-cause mortality? STUDY DESIGN AND METHODS: We evaluated 712 patients who received antibiotics for 6 or more months after diagnosis of NTM-PD between July 1997 and December 2013. Data on the waiting period, defined as the interval between diagnosis and treatment initiation, and on outcomes such as culture conversion by 6 months or death were collected. Factors associated with outcomes were analyzed after adjusting for disease severity, using the BMI, age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES) system. RESULTS: Thirty-eight percent of study patients had mild disease, 48% had moderate disease, and 14% had severe disease. The median waiting period without antibiotics among all patients was 4.8 (interquartile range, 1.3-20.8) months. After treatment initiation, 479 (67%) patients achieved culture conversion within 6 months, and 135 (19%) patients died. In univariable and multivariable models adjusted for BACES severity, no association between the waiting period and 6-month culture conversion or death was identified. However, 6-month culture conversion demonstrated a significant negative correlation with death (crude hazard ratio [HR], 0.46, 95% CI, 0.33-0.65; adjusted HR, 0.51, 95% CI, 0.35-0.74). In the subgroup treated for more than 12 months, 12-month culture conversion was also associated with reduced death (adjusted HR, 0.51; 95% CI, 0.33-0.78). INTERPRETATION: It may be reasonable to start antibiotics according to the "watchful waiting" strategy for NTM-PD, but given the survival benefits, achieving culture conversion is an important goal for patients in need of treatment.

In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease.

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 Mycobacterium avium, 53/57 M. intracellulare, 49/52 M. kansasii, 22/64 M. abscessus, and 57/67 M. massiliense). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 M. abscessus, 9/9 M. massiliense, 0/1 M. avium, and 1/1 M. intracellulare). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, p = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.

Effect of perioperative bronchodilator therapy on postoperative pulmonary function among lung cancer patients with COPD.

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; - 161.1 mL [- 240.2, - 82.0], - 179.2 mL [- 252.1, - 106.3], - 128.8 mL [- 193.2, - 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.

Outcomes of Inhaled Amikacin-Containing Multidrug Regimens for Mycobacterium abscessus Pulmonary Disease.

BACKGROUND: Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics. RESEARCH QUESTION: What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens? STUDY DESIGN AND METHODS: We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form. RESULTS: Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]). INTERPRETATION: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Clinical characteristics and treatment outcome of Candida tracheobronchitis.

ABSTRACT: Although Candida species can cause invasive fungal diseases, such as disseminated infection and pneumonia, they rarely cause tracheobronchitis, which is often fatal.To identify the clinical characteristics of Candida tracheobronchitis, we retrospectively evaluated 8 patients who had pathologically proven Candida tracheobronchitis.Their median age was 64 (range: 51-70) years and 5 were females. Three patients had solid cancers and 5 had hematological malignancies. We classified tracheobronchitis into localized and diffuse types. Of the 8 patients, 5 had localized and 3 had diffuse tracheobronchitis. While all patients with diffuse tracheobronchitis had predisposing risk factors for invasive fungal disease, such as prolonged corticosteroid use, recent use of nucleoside analogues, or recent neutropenia (<500/m3), only 2 of the 5 with localized tracheobronchitis had predisposing risk factors. Four of the 5 patients with localized tracheobronchitis had loco-regional bronchial mucosal damage (e.g., radiation or photodynamic therapy). Although all 8 patients ultimately died, some improved with or without antifungal treatment. Two of the 5 patients (1 with localized and the other with diffuse tracheobronchitis) who received antifungal agents improved after treatment, and 1 patient with localized tracheobronchitis who did not receive antifungal treatment improved spontaneously. Two of the 3 patients with diffuse tracheobronchitis did not respond to antifungal treatment.Candida tracheobronchitis can present as both localized and diffuse types. While the former was influenced more by loco-regional mucosal damage, the latter was influenced more by the patient's immune status. The treatment outcomes were especially poor in patients with diffuse tracheobronchitis.