Electronic cigarettes: a task force report from the European Respiratory Society.

There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as "electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact; and animal studies; and user perspectives.

Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by the Subfamily of Tumor Suppressor Genes.

T-box (TBX) transcription factors are evolutionary conserved genes and master transcriptional regulators. In mammals, TBX2 subfamily (TBX2, TBX3, TBX4, and TBX5) genes are expressed in the developing lung bud and tracheae. Our group previously showed that the expression of TBX2 subfamily was significantly high in human normal lungs, but markedly suppressed in lung adenocarcinoma (LUAD).

An airway epithelial IL-17A response signature identifies a steroid-unresponsive COPD patient subgroup.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation. This inflammation may persist even after smoking cessation and responds variably to corticosteroids. Personalizing treatment to biologically similar "molecular phenotypes" may improve therapeutic efficacy in COPD.

Active-to-Sedentary Behavior Transitions, Fatigability, and Physical Functioning in Older Adults.

Background: With aging, daily physical activity (PA) becomes less frequent and more fragmented. Accumulation patterns of daily PA-including transitions from active-to-sedentary behaviors-may provide important insights into functional status in older, less active populations.

Methods: Participants of the Baltimore Longitudinal Study of Aging (n = 680, 50% male, aged 27-94 years) completed a clinical assessment and wore an Actiheart accelerometer.

Job strain and cognitive change: the Baltimore Epidemiologic Catchment Area follow-up study.

Objectives: To investigate the association between job strain and subsequent cognitive change over approximately 11 years, using data from the population-based Baltimore Epidemiologic Catchment Area follow-up study.

Methods: The sample ranged from 555 to 563 participants, depending on the outcome, who reported psychosocial characteristics corresponding to the full-time job they held at baseline (1993-1996). Overall cognitive performance was measured by the Mini-Mental State Examination (MMSE), and verbal memory was measured by the ImmediateWord Recall Task and Delayed Word Recall Task at baseline and follow-up (2004-2005).

Napping characteristics and cognitive performance in older adults.

Objectives: To determine the association of napping intention, frequency, and duration with cognition in a nationally-representative sample of US older adults.

Methods: We performed a cross-sectional analysis of community-dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013-2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past-month napping intention (intentional/unintentional), napping frequency (rarely/never [non-nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31-60 minutes [moderate]; and > 60 minutes [long]).

Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1).

Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer (NSCLC) most likely to respond to single-agent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC.

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.

Methods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily.

Cell-Free DNA Next-Generation Sequencing Prediction of Response and Resistance to Third-Generation EGFR Inhibitor.

Introduction: The genomic alterations driving resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) are not well established, and collecting tissue biopsy samples poses potential complications from invasive procedures. Cell-free circulating DNA (cfDNA) testing provides a noninvasive approach to identify potentially targetable mechanisms of resistance. Here we utilized a 70-gene cfDNA next-generation sequencing test to interrogate pretreatment and progression samples from 77 EGFR-mutated non-small cell lung cancer (NSCLC) patients treated with a third-generation EGFR TKI.

Clinicopathologic Features of Non-Small-Cell Lung Cancer Harboring an Gene Fusion.

Purpose: Gene rearrangements involving can generate fusion oncoproteins containing the kinase domains of TRKA/B/C, respectively. These fusions are rare in non-small cell lung cancer (NSCLC), with frequency previously estimated to be <1%. Inhibition of TRK signaling has led to dramatic responses across tumor types with fusions.

Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET.

Study Objectives: To determine the association of excessive daytime sleepiness (EDS) and napping with subsequent brain β-amyloid (Aβ) deposition in cognitively normal persons.

Methods: We studied 124 community-dwelling participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-report measures of EDS and napping at our study baseline and underwent [11C] Pittsburgh compound B positron emission tomography (PiB PET) scans of the brain, an average ±standard deviation of 15.7 ± 3.

microRNA-mRNA regulatory networks underlying chronic mucus hypersecretion in COPD.

Chronic mucus hypersecretion (CMH) is a common feature in chronic obstructive pulmonary disease (COPD) and is associated with worse prognosis and quality of life. This study aimed to identify microRNA (miRNA)-mRNA regulatory networks underlying CMH.The expression profiles of miRNA and mRNA in bronchial biopsies from 63 COPD patients were associated with CMH using linear regression.

Impact of acute exposure to cigarette smoke on airway gene expression.

Background: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases.

Methods: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.

Sleep duration and C-reactive protein: Associations among pregnant and non-pregnant women.

Pregnant women experience more sleep disturbances and greater systemic inflammation than non-pregnant women. However, the few studies that have examined the links between sleep and inflammation in pregnant women have been in clinical samples. We examined whether sleep duration is associated with C-reactive protein (CRP) levels, a marker of inflammation, in pregnant and non-pregnant women in a population-based sample of US women.

Signature program: a platform of basket trials.

Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation.

Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).

Introduction: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses.

Summarizing performance for genome scale measurement of miRNA: reference samples and metrics.

Background: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls.

The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection.

Lung cancer remains the leading cause of cancer-related death due to its advanced stage at diagnosis. Early detection of lung cancer can be improved by better defining who should be screened radiographically and determining which imaging-detected pulmonary nodules are malignant. Gene expression biomarkers measured in normal-appearing airway epithelium provide an opportunity to use lung cancer-associated molecular changes in this tissue for early detection of lung cancer.

Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process.

Disturbed sleep and diabetes: A potential nexus of dementia risk.

Type 2 diabetes (T2D) and sleep disturbance (e.g., insomnia, sleep-disordered breathing) are prevalent conditions among older adults that are associated with cognitive decline and dementia, including Alzheimer's disease (AD).

Genome-Wide Gene Expression Changes in the Normal-Appearing Airway during the Evolution of Smoking-Associated Lung Adenocarcinoma.

Smoking perpetuates in cytologically normal airways a molecular "field of injury" that is pertinent to lung cancer and early detection. The evolution of airway field changes prior to lung oncogenesis is poorly understood largely due to the long latency of lung cancer in smokers. Here, we studied airway expression changes prior to lung cancer onset in mice with knockout of the gene () and tobacco carcinogen (NNK) exposure and that develop the most common type of lung cancer, lung adenocarcinoma, within 6 months following exposure.