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Dámaso Parrón Collar,1 Mario Pazos Guerra,1 Paula Rodriguez,1,2 Carolina Gotera,1,2 Ignacio Mahíllo-Fernández,2 Germán Peces-Barba,1,2 Luis M Seijo1,2 1Pulmonary Department, Universidad Autónoma de Madrid, 2Pulmonary Department, Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, CIBERES, Madrid, Spain Introduction: Many patients with COPD are underdiagnosed, including patients with coexisting lung cancer. Methods: We conducted a retrospective study of COPD prevalence and outcomes among all patients diagnosed with lung cancer at our institution during a 2-year period. Patients with known COPD (group A) were compared with those who received a diagnosis of COPD at the time of their oncologic workup (group B). Results: A total of 306 patients were diagnosed with lung cancer during the study period, including 87 with COPD (28.6%). Sixty percent of patients with coexisting lung cancer and COPD were unaware of their obstructive airways disease prior to the lung cancer diagnosis. Patients in group A were older (74+9 vs 69+9 years; P=0.03), had more severe obstruction (% of predicted forced expiratory volume in one second [FEV1%] 55+17 vs 71+13; P=0.04), more emphysema (91% vs 65%; P=0.02), and worse diffusing capacity of the lungs for carbon monoxide 59+19% vs 72+22%; P=0.01) than patients in group B, but the latter had more advanced lung cancer (27.3% vs 13.8% stage IV disease; P=0.01) and consumed more outpatient resources (P=0.03). Overall mortality was similar (56% vs 58%). However, stage-adjusted mortality showed a trend toward greater mortality in group B patients (1.87 [0.91–3.85]; P=0.087). Conclusion: COPD infradiagnosis is common in patients with coexisting lung cancer and is associated with more advanced cancer stage, greater outpatient resource consumption, and may be associated with greater stage-adjusted mortality. Keywords: lung cancer, COPD, underdiagnosis, staging, survival

Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts., Methods: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated., Results: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively., Conclusions: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice., (Copyright © 2023 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood. To quantify it, we define a diversity index as a potential biomarker of response. This parameter correlates with elevated activated monocytic cells and decreased granulocytic phenotypes. High-throughput profiling of soluble factors in plasma identifies fractalkine (FKN), a chemokine involved in immune chemotaxis and adhesion, as a biomarker of response to immunotherapy that also correlates with myeloid cell diversity in human patients and murine models. Secreted FKN inhibits lung adenocarcinoma growth in vivo through a prominent contribution of systemic effector NK cells and increased tumor immune infiltration. FKN sensitizes murine lung cancer models refractory to anti-PD-1 treatment to immune checkpoint blockade immunotherapy. Importantly, recombinant FKN and tumor-expressed FKN are efficacious in delaying tumor growth in vivo locally and systemically, indicating a potential therapeutic use of FKN in combination with immunotherapy., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

The European Respiratory Society (ERS) celebrated the return of an in-person meeting in Barcelona, Spain, after 2 years of virtual congresses. The ERS Congress 2022 programme was replete with symposia, skills workshops and abstract presentations from all 14 assemblies, encompassing over 3000 abstracts presented in the form of thematic poster discussion and oral presentations. In this article, highlights from the ERS Congress 2022 (including from thematic poster sessions, oral presentations and symposia from keynote speakers), presented by Assembly 5 (Airway diseases, asthma, COPD and chronic cough), are reviewed by Early Career Members and experts in the field, with the aim of presenting key recent findings in the field., Competing Interests: Conflict of interest: A. Portacci declares honoraria from AstraZeneca, GlaxoSmithKline, Chiesi and Sanofi. C. Gotera declares payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from AstraZeneca and GlaxoSmithKline. L. Uller reports payment or honoraria from AstraZeneca for lectures, presentations, speakers’ bureaus, manuscript writing or educational events. P. Pobeha declares payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca and Angeliny, is secretary of Group 05.02 (monitoring airway disease) of the European Respiratory Society, and a member of steering committees of the Slovak respiratory society and Slovak sleep medicine society. R.J. Snelgrove declares grants from The Wellcome Trust. G-J. Braunstahl reports attending advisory boards for GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim and Sanofi, honoraria from Novartis, AstraZeneca, Chiesi, GlaxoSmithKline, Teva and ALK Abello, participating in research with GlaxoSmithKline, Chiesi, AstraZeneca, ALK Abello, Novartis and Teva, and attending international conferences with Novartis and Teva. A. Bossios declares honoraria for advisory board meetings from GSK, AstraZeneca, Teva, Novartis and Sanofi, is a member of the steering committee of SHARP, secretary of Assembly 5 (airway diseases, asthma, COPD and chronic cough) of the European Respiratory Society and vice-chair of the Nordic Severe Asthma Network. O. Usmani reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi and GlaxoSmithKline, personal fees from Napp, Mundipharma, from Sandoz and Takeda, grants from Edmond Pharma, and personal fees from Cipla, Covis, Novartis, Mereo Biopharma, Orion, Menarini, UCB, Trudell Medical, Deva, Kamada, Covis and Kyorin, outside the submitted work; and is chair of Assembly 5 (airway diseases, asthma, COPD and chronic cough) of the European Respiratory Society. A. Beech, F.L.M. Ricciardolo, B. Herrero-Cortina, A.G. Mathioudakis and S. Ananth declare no conflicts of interest., (Copyright ©The authors 2023.)

Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated. First, we assessed IGF1R genomic alterations and expression in NSCLC patient tissue samples, as well as IGF1R serum levels. Next, we performed tumor heterotopic transplantation and pulmonary metastases in IGF1R-deficient mice using melanoma and Lewis lung carcinoma (LLC) cells. Herein we report increased amplification and mRNA expression, as well as increased protein expression (IGF1R/p-IGF1R) and IGF1R levels in tumor samples and serum from NSCLC patients, respectively. Moreover, IGF1R deficiency in mice reduced tumor growth, proliferation, inflammation and vascularization, and increased apoptosis after tumor heterotopic transplantation. Following induction of lung metastasis, IGF1R-deficient lungs also demonstrated a reduced tumor burden, and decreased expression of tumor progression markers, p-IGF1R and p-ERK1/2. Additionally, IGF1R-deficient lungs showed increased apoptosis and diminished proliferation, vascularization, EMT and fibrosis, along with attenuated inflammation and immunosuppression. Accordingly, IGF1R deficiency decreased expression of p-IGF1R in blood vessels, fibroblasts, tumor-associated macrophages and FOXP3 + tumor-infiltrating lymphocytes. Our results demonstrate that IGF1R promotes metastatic tumor initiation and progression in lung TME. Furthermore, our research indicates that IGF1R could be a potential biomarker for early prediction of drug response and clinical evolution in NSCLC patients., (© 2022. The Author(s).)

The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers., Competing Interests: Conflict of interest: A.G. Mathioudakis has nothing to disclose. Conflict of interest: L.E.G.W. Vanfleteren reports grants and personal fees from AstraZeneca, and personal fees from Novartis, GSK, Chiesi, Menarini, Pulmonx, Resmed, Boehringer, Verona Pharma and AGA Linde outside the submitted work. Conflict of interest: L. Lahousse reports Society awards sponsored by AstraZeneca and Chiesi; and has provided expert consultation for Boehringer Ingelheim GmbH and Novartis, outside the submitted work. Conflict of interest: A. Higham reports personal fees from Chiesi Pharmaceuticals, outside the submitted work. Conflict of interest: J.P. Allinson reports personal fees from Pulmonx, and non-financial support from GSK and Boehringer Ingelheim, outside the submitted work. Conflict of interest: C. Gotera has nothing to disclose. Conflict of interest: D. Visca has nothing to disclose. Conflict of interest: D. Singh reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Glenmark, Menarini, Mundipharma, Novartis, Pfizer, Pulmatrix, Therevance and Verona, and personal fees from Cipla, Genentech and Peptinnovate, outside the submitted work. Conflict of interest: A. Spanevello has nothing to disclose., (Copyright ©ERS 2020.)

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Study Objectives: To identify a link between sleep disordered breathing, nocturnal hypoxemia, and lung cancer., Methods: We conducted a cross-sectional study of a combined cohort of 302 individuals derived from the sleep apnea in lung cancer study (SAIL; NCT02764866) investigating the prevalence of sleep apnea in lung cancer, and the sleep apnea in lung cancer screening study (SAILS; NCT02764866) investigating the prevalence of sleep apnea in a lung cancer screening program. All subjects had spirometry and a chest CT, underwent home sleep apnea testing (HSAT), and completed a sleep related questionnaire. Subjects from the SAIL study underwent HSAT prior to initiating oncologic therapy or surgery. Subjects with an apnea-hypopnea index (AHI) > 15 were compared with a control group of individuals with an AHI < 15. Propensity score, near neighbor matching, and logistic regression adjusted for potential confounders, were used in order to evaluate the association between sleep apnea, the AHI, oxygen desaturation indices and lung cancer., Results: The prevalence of sleep apnea and lung cancer in the combined cohort was 42% and 21%, respectively. Lung cancer was 8% more prevalent in patients with an AHI >15. The difference was statistically significant when assessed by propensity score matching (p = 0.015) and nearest neighbor matching (p = 0.041). Binary logistic regression adjusted for potential confounders revealed a statistically significant association between AHI (p = 0.04), nocturnal hypoxemia, including time spent below 90% oxyhemoglobin saturation (T90%; p = 0.005), 3% oxygen desaturation index (ODI3; p = 0.02) and lung cancer., Conclusions: Sleep apnea and nocturnal hypoxemia are associated with an increased prevalence of lung cancer., Clinical Trial Registration: SAIL study (NCT02764866) and SAILS study (NCT02764866)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Obstructive sleep apnea (OSA) has been linked to tumorigenesis and tumor progression., Objectives: The Sleep Apnea in Lung Cancer (SAIL) study (NCT02764866) was designed to determine the prevalence of OSA in patients with lung cancer., Methods: Cross-sectional study including consecutive patients with newly diagnosed lung cancer. All patients were offered home sleep apnea testing (HSAT) and administered a sleep-specific questionnaire prior to initiating oncologic treatment. Sleep study-related variables, symptoms, and epidemiologic data as well as cancer related variables were recorded., Results: Eighty-three patients were enrolled in the SAIL study. Sixty-six completed HSAT. The mean age was 68 ± 11 years and 58% were male with a mean body mass index of 28.1 ± 5.4. Forty-seven percent were current smokers, 42% former smokers, and 11% never smokers with a median tobacco consumption of 51 pack-years. Fifty percent had COPD with a mean FEV1 of 83 ± 22.6% of predicted and a mean DLCO of 85.5 ± 20.1%. Adenocarcinoma was the most common histologic type (46.7%), followed by squamous cell (16.7%) and small cell (16.7%). Most patients were diagnosed at an advanced stage (65% in stages III-IV). The vast majority (80%) had OSA (apnea-hypopnea index [AHI] > 5), and 50% had moderate to severe OSA (AHI > 15) with a mean Epworth Sleepiness Score of 7.43 ± 3.85. Significant nocturnal hypoxemia was common (Median T90: 10.9% interquartile range 2.4-42.2)., Conclusions: Sleep apnea and nocturnal hypoxemia are highly prevalent in patients with lung cancer., (© 2018 S. Karger AG, Basel.)