COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

The differential risk of pneumonia among inhaled corticosteroid (ICS) use in patients with COPD requires more investigation, especially regarding beclomethasone-containing inhalers. The goal of this study was to compare the risk and benefit profile of different ICS/long-acting β2-agonist (LABA) combinations in patients with COPD.

The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because it shares genetic, histopathologic, and radiographic features with the fibrosing interstitial lung disease seen in rheumatoid arthritis (RA), the goal of this study was to investigate RA-related autoantibodies in IPF.

Sleep is important to health and well-being, and studies in healthy adults have demonstrated that sleep deprivation impacts respiratory, immune, and cognitive function. Historically, because of the nature of critical illness, sleep has not been considered a priority for patient care in the ICU. More recently, research has demonstrated that sleep is markedly abnormal in patients who are critically ill. In addition, there is often disruption of circadian rhythms. Delirium is a syndrome of acute alteration in mental status that occurs in the setting of contributing factors such as serious illness, medication, and drug or alcohol intoxication or withdrawal. Delirium is a frequent occurrence in critical illness, and research has demonstrated several adverse outcomes associated with delirium including persistent cognitive impairment and increased mortality. Sleep deprivation and delirium share many common symptoms. The similarity in symptoms between sleep disruption and delirium have prompted experts to draw links between the two and question both the relationship and its direction. In addition, the inclusion of sleep disturbance to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition in its constellation of symptoms used in diagnosing delirium has increased awareness of the link between sleep and delirium. This paper will review the literature on sleep in critical illness and the potential mechanisms and pathways that may connect sleep and delirium.

Venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) after refractory cardiogenic shock or cardiac arrest has significant morbidity and mortality. Early outcome prediction is crucial in this setting, but data on neuroprognostication are limited. We examined the prognostic value of clinical neurologic examination, using an automated device for the quantitative measurement of pupillary light reactivity.

Sleep health is a multidimensional construct that includes adequate duration, quality, and appropriately timed sleep that may be influenced by environmental factors. In this review, we focus on how an individual's living and sleeping environment, both the surrounding neighborhood physical and social features and the atmosphere around them, may impact their sleep health. We explore the associations of the physical environment (urban density, recreational facilities, green space, mixed land use, and healthy food stores), neighborhood deprivation (disadvantage and disorder), and the social environment (social cohesion, safety, and stigma) with sleep in both adult and pediatric populations. We investigate how physical and social environmental features may lead to alterations in the timing, duration, and quality of sleep and contribute to the most prevalent sleep disorders: insomnia, sleep apnea, and circadian rhythm disorders. We also review how ambient factors such as artificial light, environmental noise, and air pollution may contribute to sleep pathology. We have included key studies and recent emerging data regarding how the differential distribution of environmental factors that may affect sleep health may contribute to sleep health disparities.

Accurate diagnosis is crucial to improve the treatment and prognosis of respiratory disease, especially lung cancer. Tumors and lesions located deep in the lung are directly accessible via dendritic tracheal bronchus, thereby opening a new way to tackle respiratory disease. Intratracheal delivery is an innovative, noninvasive approach for imaging and treating respiratory disease efficiently, when compared with other delivery methods. Intratracheal delivery of nano- and microparticles and hyperpolarized gases offers valuable clinical advantages, such as assessing lung function, monitoring ventilation and perfusion, controlling disease progression, and inhibiting tumor growth. Especially, versatile nanosized particles have enormous potential to benefit precision imaging and therapy at the molecular level. Here we discuss advances of intratracheal delivery of nano- and microparticles and hyperpolarized gases for respiratory disease imaging and treatment, with an emphasis on intratracheal nanoparticles delivery for pulmonary imaging, which has extremely valuable clinical applications in precise theranostics for respiratory disease.

Each year, > 1.5 million Americans are diagnosed with an incidentally detected lung nodule. Practice guidelines attempt to balance the benefit of early detection of lung cancer with the risks of diagnostic testing, but adherence to guidelines is low. The goal of this study was to determine guideline adherence rates in the setting of a multidisciplinary nodule clinic and describe reasons for nonadherence as well as associated outcomes.

Bronchoscopy is the gold standard for evaluating tracheomalacia; however, reliance on an invasive procedure limits understanding of normal airway dynamics. Self-gated ultrashort echo-time MRI (UTE MRI) can assess tracheal dynamics but has not been rigorously evaluated.

Neighborhood circumstances have an influence on multiple health outcomes, but the association between neighborhood conditions and lung cancer incidence has not been studied in sufficient detail. The goal of this study was to understand whether neighborhood conditions are independently associated with lung cancer incidence in ever-smokers after adjusting for individual smoking exposure and other risk factors.

Regional and/or national severe asthma registries provide valuable country-specific information. However, they are often limited in scope within the broader definitions of severe asthma, have insufficient statistical power to answer many research questions, lack intraoperability to share lessons learned, and have fundamental differences in data collected, making cross comparisons difficult. What is missing is a worldwide registry which brings all severe asthma data together in a cohesive way, under a single umbrella, based on standardized data collection protocols, permitting data to be shared seamlessly. The International Severe Asthma Registry (ISAR; http://isaregistries.org/) is the first global adult severe asthma registry. It is a joint initiative where national registries (both newly created and preexisting) retain ownership of their own data but open their borders and share data with ISAR for ethically approved research purposes. Its strength comes from collection of patient-level, anonymous, longitudinal, real-life, standardized, high-quality data (using a core set of variables) from countries across the world, combined with organizational structure, database experience, inclusivity/openness, and clinical, academic, and database expertise. This gives ISAR sufficient statistical power to answer important research questions, sufficient data standardization to compare across countries and regions, and the structure and expertise necessary to ensure its continuance and the scientific integrity and clinical applicability of its research. ISAR offers a unique opportunity to implement existing knowledge, generate new knowledge, and identify the unknown, therefore promoting new research. The aim of this commentary is to fully describe how ISAR may improve our understanding of severe asthma.

Although counties are the smallest geographic level for comprehensive health-care delivery analysis, little is known about county-level variations in receipt of curative-intent surgery for early-stage non-small cell lung cancer (NSCLC) and factors contributing to such variations in the United States.

Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging, requiring a balance between thromboembolism prevention and serious bleeding. Comparisons of nonvitamin K antagonist oral anticoagulants (NOACs) and warfarin in older adults at different age strata (65-74, 75-89, and ≥ 90 years of age) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared with warfarin for stroke prevention in elderly patients with AF.

Established reference standards for the ventilatory threshold (Vt) are lacking. The aim of this study was to develop reference standards for the Vt derived from cardiopulmonary exercise testing (CPX) using treadmill and cycle ergometry.