Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia.

BACKGROUND: Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. METHODS: The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. RESULTS: A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05). CONCLUSIONS: Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Bone-modifying agents for non-small-cell lung cancer patients with bone metastases during the era of immune checkpoint inhibitors: A narrative review.

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non-small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer.

Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.

Smoking Status at Time of Diagnosis Affects the Efficacy of Anti-PD-1/L1 Therapy in Patients With Advanced NSCLC.

BACKGROUND/AIM: Programmed death ligand-1 (PD-L1) expression is known to be a predictive biomarker for response to immunotherapy in non-small cell lung cancer (NSCLC). However, PD-L1 is not always a reliable predictive biomarker. In the present study, we aimed to compare responses to immunotherapy according to smoking status in NSCLC patients receiving immunotherapy in second line or further line treatment. PATIENTS AND METHODS: The lung cancer registry database of the Catholic Medical Center, Seoul, Republic of Korea was used. Patients were eligible for this study if they were diagnosed with histologically confirmed NSCLC and received immune checkpoint inhibitors (ICIs) as second-line or further line therapy from January 2017 to December 2021. RESULTS: Overall, 220 patients with NSCLC treated with ICIs were enrolled. There were 40 never smokers, 73 former smokers, and 107 current smokers. In multivariate analysis, smoking status, pathologic type, and PD-L1 expression were significant factors affecting PFS. Sex, ECOG performance status, pathologic type, and PD-L1 expression were significant factors affecting OS. CONCLUSION: Smoking status at diagnosis of lung cancer could be a predictive biomarker for response to ICIs in patients with advanced NSCLC.

Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer.

Background and Objective: Immune checkpoint inhibitors (ICI) were a major clinical advancement that provided an opportunity to improve the prognosis of patients with non-small cell lung cancer (NSCLC). However, programmed death-ligand-1 (PD-L1) expression does not sufficiently predict ICI efficacy in NSCLC patients. In recent studies, the tumor immune microenvironment (TIME) was shown to have a central role in lung cancer progression and to affect clinical outcome of patients diagnosed with lung cancer. As development of new therapeutic targets to overcome ICI resistance is a priority, understanding the TIME is important. Recently, a series of studies was conducted to target each component of TIME to improve efficacy of cancer treatment. In this review, important features related to TIME, its heterogeneity and current trends in treatment targeting the component of TIME are discussed. Methods: PubMed and PMC were searched from January 1st, 2012 to August 16th, 2022 using the following key words: "NSCLC", "Tumor microenvironment", "Immune", "Metastasis" and "Heterogeneity". Key Content and Findings: Heterogeneity in the TIME can be either spatial or temporal. Subsequent to heterogeneous changes in the TIME, treatment of lung cancer can be more challenging because drug resistance is more likely to occur. In terms of the TIME, the main concept for increasing the chance of successful NSCLC treatment is to activate immune responses against tumor cells and inhibit immunosuppressive activities. In addition, relevant research is focused on normalizing an otherwise aberrant TIME in NSCLC patients. Potential therapeutic targets include immune cells, cytokine interactions, and non-immune cells such as fibroblasts or vessels. Conclusions: In management of lung cancer, understanding TIME and its heterogeneity is significant to treatment outcomes. Ongoing trials including various treatment modalities such as radiotherapy, cytotoxic chemotherapy, and anti-angiogenic treatment and regimens inhibiting other immunoinhibitory molecules are promising.

Association Between Quality of Life Questionnaire at Diagnosis and Survival in Patients With Lung Cancer.

BACKGROUND: Patients with lung cancer experience considerable symptom burden, which can decrease patients' QOL. Our aim was to investigate the association between QOL questionnaire at diagnosis and survival of lung cancer. PATIENTS AND METHODS: This was a multicenter study of lung cancer patients at 7 medical centers of the Catholic University of Korea that responded to a quality of life questionnaire between December 1, 2017 and December 31, 2020. We analyzed 5 functional (physical, role, emotional, cognitive, and social functioning) and nine symptom (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) scales and examined their associations with survival. A Cox proportional hazards model was used to evaluate the prognostic value. RESULTS: In total, 1297 lung cancer patients were enrolled. The results of multivariable analysis showed that female, younger age, never smoker, stage I or II cancer, higher physical functioning, and emotional functioning were statistically significant favorable predictors for survival. On subgroup analysis according to early (stage I and II) or advanced (stage III or IV) stage, higher physical functioning and emotional functioning were each found to be favorable prognostic factors for survival. Meanwhile, fatigue, pain, insomnia, and financial difficulties were found to be associated with low scores on the emotional functioning scale; fatigue, pain, dyspnea, and financial difficulties were associated with low scores on the physical functioning scale. CONCLUSION: Assessing the physical functioning and emotional functioning scales of QOL questionnaire items at diagnosis can help clinicians predict the survival of patients with lung cancer.

Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.

BACKGROUND: The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma. METHODS: The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP3) receptors (IP3R) with treating lipopolysaccharide (LPS) and TIO. RESULTS: Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP3 receptor levels. After TIO treatment, recovery of IP3R and improved PLCγ-1 levels were observed. CONCLUSION: These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP3-IP3R mediated intracellular calcium ion pathway.

The association between clinical parameters and resectability in stage III non-small cell lung cancer, and a combination of N2 lymph node burden and lung immune prognostic index score as a potential biomarker.

Background: Surgery is important treatment option for stage III non-small cell lung cancer (NSCLC) because of its curative potential. We investigated the characteristics of resectable patients, and compared the outcomes according to treatment modalities. Methods: Among 1,092 patients with NSCLC diagnosed between 2008 to 2020 from 7 university hospitals of Catholic Medical Center, we retrospectively analyzed 252 patients with clinical or pathological stage III. We compared survival outcomes among the groups according to resectability, first-line treatments, and the lung immune prognostic index (LIPI) score. Clinical N2 subgroup was analyzed using multi-parameter scoring system. Results: The resectable group consisted of less smokers, showed better pulmonary function and lower inflammatory markers, and tended to be diagnosed as earlier cancer stage than the unresectable group. The resectable group showed better progression-free survival (PFS) and overall survival (OS) than the unresectable group (P<0.001 and P<0.001, respectively). Regarding the first-line treatment, surgery showed the longest median PFS (33.70 months) and the highest 12-month OS rate (91.6%) than the other treatment modalities. OS was significantly different depending on the LIPI score in whole population, as well as in the unresectable group (P=0.004 and P=0.003, respectively). LIPI 0 group exhibited better OS than LIPI 1 and 2 in both populations. Eastern Cooperative Oncology Group (ECOG) 2-4, LIPI 1-2, and first-line treatment were independent prognostic factors for OS. Smoking, forced expiratory volume in the first second (FEV1) and more advanced cancer stage were associated with unresectability. In subgroup analysis of N2 disease, we attempted to create new scoring system combining lymph node (LN) status and LIPI score. This scoring system showed significant association with OS. Conclusions: The patients with resectable stage III NSCLC showed better PFS and OS than the patients with unresectable tumor. LIPI score exhibited possibility to be used as potential biomarker in stage III NSCLC. The multi-parameter scoring system using LN status and LIPI score was predictive of OS in the N2 subgroup.

Update on Adjuvant Treatment in Resectable Non-Small Cell Lung Cancer and Potential Biomarkers Predicting Postoperative Relapse.

A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015.

PURPOSE: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. MATERIALS AND METHODS: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. RESULTS: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). CONCLUSION: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

Evaluation of asthma-chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease.

BACKGROUND: Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma- chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO. METHODS: We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system. RESULTS: Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase-associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model. CONCLUSION: We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide-platinum-atezolizumab treatment.

BACKGROUND: The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy. METHODS: Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant. RESULTS: A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant. CONCLUSION: In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors.

Efficacy and safety of first-line anlotinib-based combinations for advanced non-small cell lung cancer: a three-armed prospective study.

Background: The evidence of combined therapies of multi-target agents in first-line treatment of advanced non-small cell lung cancer (NSCLC) was limited. This study aimed to evaluate the safety and efficacy of anlotinib combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), chemotherapy, or immune checkpoint inhibitor (ICI) in advanced NSCLC. Methods: This open-label, three-arm, prospective study (NCT03628521) enrolled untreated locally advanced/metastatic NSCLC patients. Patients with EGFR mutation NSCLC received anlotinib and erlotinib (cohort A). Patients without EGFR/ALK/ROS1 mutation received anlotinib combined with carboplatin plus pemetrexed/gemcitabine (cohort B), or sintilimab (cohort C). The primary outcomes were safety and objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Treatments were performed for at least 2 cycles and efficacy was evaluated every 2 cycles using RECIST version 1.1. Safety was assessed throughout the study. Results: A total of 30, 30, and 22 patients were enrolled in cohorts A, B, and C, respectively. There were 3 patients did not complete the treatment in cohort A. In cohorts A and B, ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 77.3% and 60.0% of patients, respectively. The most common TRAEs were rash (10.0%) and decreased platelet count (30.0%) in cohorts A and B, respectively. The ORRs were 92.9% and 60.0% in cohorts A and B, respectively, and DCRs were 96.4% and 96.7%, respectively. The ORR and incidence of ≥ grade 3 TRAEs of cohort C were, which 72.7% and 54.5%, which had been published previously. Median PFSs [95% confidence interval (CI)] were 21.6 (15.6 to 24.9), 13.0 [10.5 to not estimated (NE)], and 15.6 (12.9 to NE) months in cohorts A, B, and C, respectively. Median OS was 28.1 (95% CI: 21.82 to NE) months in cohort B. The 24-month OS rates in cohorts A and C were 87.1% and 83.9%, respectively. Conclusions: Anlotinib-based combinations with EGFR-TKI, chemotherapy, and ICI are well-tolerated and encouraging as first-line therapies for advanced NSCLC, which could be verified in future studies. Anlotinib-based combination might provide multiple choices for first-line treatment in patients with advanced NSCLC.

Immune checkpoint inhibitor-related interstitial lung disease in patients with advanced non-small cell lung cancer: systematic review of characteristics, incidence, risk factors, and management.

Background: Immune checkpoint inhibitors (ICIs) are widely used in cancers with or without other treatments. Immune-related adverse events (irAEs) have been reported as side effects of ICIs and involve various organs. Pneumonitis, which is also called ICI-related interstitial lung disease (ILD), is one of the life-threatening adverse events. In this report, we reviewed the safety of ICIs and risk factors for ICI-related ILD in non-small cell lung cancer (NSCLC) patients. Methods: Databases (The National Center for Biotechnology Information, PubMed, Cochrane Library, Google Scholar, and Embase) were searched for the literature on pulmonary adverse events and immunotherapy following PRISMA guidelines. All studies published in English between January 2016 and June 2021 were included. Results: One-hundred twenty-five articles were included at final. Pre-existing ILD as well as asthma and chronic obstructive lung disease (COPD) were associated with high risk for the development of ICI-related ILD, however, it did not affect the prognosis. The treatment of ICI-related ILD is different according to the severity grades, which includes discontinuation of ICI, corticosteroids, and for steroid-refractory ILD, other immunosuppressants. Rechallenging of ICI should be carefully considered in selected patients. Discussion: Patients with pre-existing lung disease and poor lung function need more attention for the development of ICI-related ILD. It is necessary to be aware of clinical manifestation of ICI-related ILD with prompt management.

Clinical relevance of false-negative interferon-gamma release assays in patients with tuberculous pleurisy in an intermediate tuberculosis burden country.

Background: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB). Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included. Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]. Conclusions: In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.

Narrative review: association between lung cancer development and ambient particulate matter in never-smokers.

Objective: To review the association and pathophysiological link between lung cancer in never smokers and ambient particulate matter (PM). Background: Although the association between exposure to PM and lung cancer development is well known, the pathophysiological background is yet to be studied in depth. Never smokers comprise a large proportion of newly diagnosed lung cancer cases and account for 25% of all cases. Considering the carcinogenic nature of ambient PM and the fact that many patients with lung cancer are never smokers, it is necessary to evaluate the interrelation and possible clinical background, in order to effectively prevent lung cancer development in this subgroup. Methods: An online search of literature was conducted. The National Center for Biotechnology Information (NCBI), PubMed, Google Scholar, Cochrane Library and EMBASE were searched. Conclusions: In never smokers, the risk of lung cancer was dose-dependent with the concentration of ambient air pollutants. Regarding the pathophysiological link, involvement of epithelial mesenchymal transition (EMT) and chronic inflammation has been mentioned, but further studies are necessary to enable therapeutic interventions to prevent cancer development. Considering the significant burden of PM on lung cancer development, both public and clinical approaches to cancer prevention are essential. To prevent lung cancer more effectively, clinicians should develop a more individualized approach in patients, focusing on gender and genetic background.