Efficacy of cross-line anti-programmed death 1/programmed cell death-ligand 1 antibody in the treatment of advanced nonsmall cell lung cancer: A retrospective study.

Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

Association of high-sensitivity CRP and FEV1%pred: a study on non-pulmonary disease in a population in Beijing, China.

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.

Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community.

OBJECTIVE: This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. METHODS: Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40-75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. RESULTS: A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245-2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. CONCLUSION: These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.

Imaging Mass Cytometry Analysis of immune Checkpoint Inhibitor-Related Pneumonitis: A Case Report.

Immune checkpoint inhibitor-related pneumonitis (CIP) is a rare but well-recognized immune-related adverse event (irAE), causes 35% of irAE related deaths. However, the mechanism of CIP remains unclear and no evidence-based treatment except for glucocorticoids is available. Herein, we report the case of a patient with metastatic bladder cancer who received tislelizumab and was diagnosed with CIP. The patient underwent transbronchial cryobiopsy. The patient was treated with glucocorticoid, but CIP recurred when the glucocorticoid tapering. The paraffine-embedded lung tissue was sectioned, stained with 31 heavy-metal tagged antibodies, and analyzed using imaging mass cytometry (IMC) technology. We identified multiple immune cell subsets in the lung tissue and observed the infiltration of memory T cells and the CD4+ DC subset. The data indicated the great potential of IMC technology in the identification and characterization of irAEs. Further investigation is warranted to identify the mechanism of action of CIP.

Clinical Outcomes of Immune Checkpoint Inhibitor Therapy in Patients With Advanced Non-small Cell Lung Cancer and Preexisting Interstitial Lung Diseases: A Systematic Review and Meta-analysis.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and preexisting interstitial lung disease (ILD) are often excluded from clinical trials of immune checkpoint inhibitors (ICIs), leaving a gap in knowledge. RESEARCH QUESTION: What are the clinical outcomes of ICIs in patients with NSCLC and preexisting ILD? STUDY DESIGN AND METHODS: Systematic searches were conducted of PubMed, EMBASE, and Cochrane Library through April 2021 with no language or study design restrictions. Studies reporting the safety and efficacy data among patients with cancer and ILD receiving ICI therapy were collected. The primary end points were clinical efficacy to immunotherapy and the incidence of immune-related adverse events, especially for checkpoint inhibitor pneumonitis (CIP). RESULTS: A total of 179 patients in 10 studies were included. The pooled overall response rate (ORR) and pooled disease control rate (DCR) were 34% (95% CI, 20-47) and 66% (95% CI, 56-75), respectively. The ORR in patients with preexisting ILD was significantly higher than that in patients without ILD (OR, 1.99; 95% CI, 1.31-3.00). The DCR and progression-free survival in patients with preexisting ILD were not inferior to those without ILD (pooled OR, 1.46; 95% CI, 0.94-2.25 for DCR). The pooled incidences of any grade and grade 3 or higher CIP were 27% (95% CI, 17-37) and 15% (95% CI, 9-22) in patients with preexisting ILD, and 10% (95% CI, 6-13) and 4% (95% CI, 2-6) in patients without ILD. Meta-analysis found a significantly higher incidence rate of any grade and grade 3 or higher CIP in patients with NSCLC and preexisting ILD than in those patients without ILD (OR, 3.23 [95% CI, 2.06-5.06]; OR, 2.91 [95% CI, 1.47-5.74]). INTERPRETATION: Programmed cell death protein 1/programmed cell death ligand 1 inhibitors had favorable efficacy in NSCLC with preexisting ILD. CIP is frequent in patients with preexisting ILD who receive ICI therapy but is often mild and easily manageable. Clinicians should be cautious when using ICIs in patients with preexisting ILD.

Bronchoscopic retrograde recanalization of complete tracheal obliteration after tracheostomy.

Complete tracheal obliteration after tracheostomy remains a considerable challenge for otolaryngologists and pulmonologists. Here, we report for the first time a novel method of interventional bronchoscopy to successfully recanalize complete tracheal obliteration. Three patients with suprastomal tracheal obliteration and tracheostomy dependence were referred to our center for further management. Using interventional bronchoscopy, a TBNA needle was retrogradely inserted from the stoma to locate the original passage through the occlusion, and then its stylet was left as a guide wire for the sequential dilations. Once the tracheal lumen was restored, endoprosthesis would be implanted to maintain the airway patency. All cases achieved successful recanalization with effortless breathing after the treatment and restored phonation. Bronchoscopic retrograde recanalization using a TBNA needle is a promising and effective treatment for complete tracheal obliteration.

Potential Role of Pleural Fluid Cytokine Profile in Myelomatous Pleural Effusions.

BACKGROUND: Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. CASE PRESENTATION: We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. CONCLUSION: There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

Primary resistance to alectinib in a patient with STRN-ALK-positive non-small cell lung cancer: A case report.

Anaplastic lymphoma kinase (ALK) rearrangements are drivers of a subset of non-small cell lung cancer (NSCLC). The rapid progression of ALK inhibitors has significantly prolonged the progression-free survival of patients with ALK gene-sensitive mutations. However, the response of patients with rare ALK rearrangements to tyrosine kinase inhibitors remains unknown. Here, we report a rare case of striatin (STRN)-ALK-positive NSCLC showing primary resistance to first-line therapy alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting.

Primary pulmonary Hodgkin's lymphoma mimicking rheumatoid arthritis-associated organizing pneumonia: A case report.

Primary pulmonary Hodgkin's lymphoma (PPHL) is an extremely rare disease. The nonspecific clinical and radiological features render the diagnosis a great challenge. Here, we present a case of PPHL mimicking rheumatoid arthritis-associated organizing pneumonia.

Identification of exosome miRNAs in bronchial epithelial cells after PM2.5 chronic exposure.

Numerous epidemiological studies have demonstrated that chronic PM2.5 exposure was associated with the lung carcinogenesis without known potential mechanisms. Exosomes-derived non-coding RNAs, including miRNAs, are proposed to play critical role in the occurrence and development of malignant diseases. So identification of exosomes-derived miRNAs could help us to better understand the molecular toxicity of PM2.5-induced lung cancer. Establishment chronic exposure animal and cell model with PM2.5 was conducted as before. HE staining was used for estimating the histological alternations of lungs in vivo. The expressions of EMT markers in vivo and vitro were quantified by Western blot. Then the exosomes in cell culture supernatant were extracted and the involved miRNAs were extracted and sequenced. The different expression level of miRNAs were verified by RT-PCR. Chronic PM2.5 exposure induced bronchial epithelial cell atypical hyperplasia and massive macrophage infiltration. PM2.5 exposure induce EMT event in vivo and vitro indicated as increased expression of Vimentin and decreased expression of E-cadherin. And five passages of PM2.5 stimulation also induced the release of rich and extractable exosomes in the cell culture supernatant in vitro. Through sequencing, there were differentially expressed 36 miRNAs between PM2.5 chronic exposed and control groups with 1.5-fold and greater differences. Among them, there were 30 exosome-miRNAs upregulated and 6 downregulated expression by PM2.5 exposure. The downregulated expression of miR-29b-2-5p, miR-193b-5p and miR-320c and upregulated expression of miR-100-5p, 125b-5p and unconservative_2_45093 in PM2.5 group were identified and reconfirmed by qRT-PCR. Chronic PM2.5 exposure causes bronchial epithelial cells atypical hyperplasia and induces EMT event in vivo, and it also induce the expression differences of miRNAs in exosome in vitro. Meanwhile, the identified differentially expressed exosome-miRNAs may partially associate with tumorigenesis. To sum up, the identified exosome-miRNAs may play role in the development of lung cancer induced by chronic PM2.5 exposure.

Long-term prognostic factors of clinical success after interventional bronchoscopy in patients with scarring central airway stenosis.

BACKGROUND: Scarring central airway stenosis (SCAS) is a potentially life-threatening condition with debilitating symptoms. Interventional bronchoscopy is increasingly used to relieve symptoms in patients with SCAS, but recurrent stenosis is frequently observed. Little data exist on the long-term prognosis of interventional bronchoscopy for SCAS. We aimed to assess the prognostic factors of bronchoscopic interventions in patients with SCAS to optimize treatment. METHODS: This was a retrospective study that enrolled 119 consecutive patients with SCAS from January 2010 to April 2019 at our institution. Long-term clinical success was defined as airway stenosis < 50%, no limitation of physical activity, and a stable condition for > 12 months after the last interventional procedure. We compared patients' demographics, airway stenosis characteristics, and interventional procedures between the successful and unsuccessful groups, and identified significant predictors of long-term outcome with univariate and multivariate logistic regression. RESULTS: A total of 119 patients with 577 therapeutic bronchoscopies were included. Seventy-five (63%) patients were considered to have long-term clinical success. Older age, male gender, smoking, elevated C-reactive protein level, subglottic stenosis, stent or T-tube implantation, previous interventional treatment, and multiple procedures per year were potentially associated with unsuccessful long-term outcomes in the univariate analysis. Current smoker status (odds ratio [OR] 5.70, 95% confidence interval [CI] 1.35-24.17, P = 0.018), subglottic stenosis (OR 4.35, 95% CI 1.31-14.46, P = 0.017), and stent implantation (OR 4.96, 95% CI 1.33-18.48, P = 0.017) were associated with decreased odds of long-term success in the multivariate logistic regression analysis. Of note, there was no significant difference in odds of success between former smokers and nonsmokers. CONCLUSIONS: Current smoker status, subglottic stenosis, and stent implantation are independent factors associated with reduced long-term efficacy of interventional bronchoscopy for SCAS. Smoking cessation should be encouraged to improve the outcome of therapeutic bronchoscopy.

Prevalence of interstitial lung disease in polymyositis and dermatomyositis: A meta-analysis from 2000 to 2020.

OBJECTIVE: Interstitial lung disease (ILD) is the most important prognostic factor for mortality in patients with polymyositis (PM) and dermatomyositis (DM), but the prevalence of ILD in PM/DM may vary between countries. The aim of this study was to determine the overall prevalence of ILD in global patients with PM/DM. METHODS: We performed a systematic literature review of studies published from Jan 1, 2000 to April 30, 2020 on ILD and PM/DM. We extracted data and pooled the prevalence by using a random-effect model due to high heterogeneity. Heterogeneity was assessed by subgroup analysis and sensitivity analysis. RESULTS: A total of 34 studies with 10,130 patients were included in our meta-analysis. Pooled data demonstrated that the global prevalence of ILD in patients with PM/DM was 0.41 (95% confidence interval [CI] 0.35-0.48). However, this prevalence varied with geographical locations and time trends. The prevalence of ILD in PM/DM was 0.5 (95% CI 0.42-0.57) in Asia, 0.23 (95% CI 0.15-0.31) in America, and 0.26 (95% CI 0.18-0.34) in Europe. A higher prevalence of ILD was reported in studies published in 2011-2015 (0.43, 95% CI 0.34-0.52) and 2016-2020 (0.45, 95% CI 0.35-0.54), compared with those published in 2000-2010 (0.27, 95% CI 0.16-0.39). The pooled prevalence of ILD in patients with DM, PM, and clinically amyopathic dermatomyositis subtype was 0.42 (95% CI 0.35-0.49), 0.35 (95% CI 0.27-0.42), and 0.53 (95% CI 0.32-0.74), respectively. Patients with anti-Jo-1 and anti-melanoma differentiation-associated gene 5 antibodies were more likely to develop ILD than other myositis-specific autoantibodies. CONCLUSION: The global prevalence of ILD in patients with PM/DM was approximately 41% and the condition was predominant in Asians. This highlights potential genetic and environmental differences in the pathogenesis of ILD in patients with PM/DM. More studies are required to elucidate the specific associations.