COPD is a common respiratory disorder that poses a major health-care burden with societal and financial ramifications. Although effective inhaled therapies are available, nonadherence is common among patients with COPD and potentially contributes to the burden of this disease. Electronic inhaler monitoring (EIM) is a novel modality that enables real-time assessment of adherence to inhaled therapy and informs the assessment of treatment effectiveness. EIM can be combined with physician feedback, automated audiovisual reminders, and text messaging to bolster adherence. Clinical studies have suggested that EIM can diagnose nonadherence, improve adherence, and predict exacerbations. Using an EIM-guided protocol has the potential to avoid treatment escalation in the nonadherent. Coupling EIM to behavioral intervention is an area of ongoing research with mixed results, with some studies showing benefit and others showing minimal or no significant change in clinical outcomes. Further investigation is necessary to understand the incremental benefits of EIM features, delineate optimal program implementation, and target patient populations that would benefit the most from monitoring.

Parasitoses are infectious diseases of global distribution, with predominance in areas of poor sanitation. Parasites cause damage through direct tissue injury and the inflammatory response generated by their migration and establishment in various organs. Thoracic involvement by parasitic disease can generate both specific and nonspecific clinical, laboratorial, and radiologic manifestations, which often makes their diagnosis challenging. The correct diagnosis is crucial for definition of treatment, which sometimes requires rapid intervention. Based on a literature review of the last few decades, this article aimed to characterize the main radiologic findings related to thoracic manifestations of parasitic diseases, correlating them with radiographic and tomographic images of patients with confirmed diagnosis of such pathologies. The included parasitic diseases are malaria, Chagas disease, toxoplasmosis, amoebiasis, ascariasis, toxocariasis, strongyloidiasis, dirofilariasis, cysticercosis, echinococcosis, schistosomiasis, and paragonimiasis.

Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of non-invasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB.

Chronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis.

The concerns regarding air leak after lung surgery or spontaneous pneumothorax include detection and duration. Prior studies have suggested that digital drainage systems permit shorter chest tube duration and hospital length of stay (LOS) by earlier detection of air leak cessation. We conducted a systematic review to assess the impact of digital drainage on chest tube duration and hospital LOS after pulmonary surgery and spontaneous pneumothorax.

Central sleep apnea/Hunter-Cheyne-Stokes breathing (CSA/HCSB) is prevalent in patients with heart failure with reduced ejection fraction (HFrEF). The acute pathobiologic consequences of CSA/HSCB eventually lead to sustained sympathetic overactivity, repeated hospitalization, and premature mortality. A few randomized controlled trials (RCTs) have shown statistically significant and clinically important reduction in sympathetic activity when CSA/HCSB is attenuated by oxygen or PAP therapy. Yet, the two largest PAP RCTs in patients with HFrEF, one with CPAP and the other with adaptive servoventilation (ASV), were negative with respect to their primary outcomes, and both were associated with excess mortality. However, both trials suffered from significant deficiencies, casting doubt on their results. A second RCT evaluating an ASV device with an advanced algorithm is ongoing. A new modality of therapy, unilateral phrenic nerve stimulation, has undergone an RCT that demonstrated an improvement in CSA that was associated with a reduction in arousals, improvement in sleepiness, and improvement in quality of life. However, a long-term mortality trial has not been performed with this modality. Most recently, the National Institutes of Health has funded a long-term, phase 3 RCT of low-flow oxygen vs sham for the treatment of CSA/HCSB in HFrEF. The composite primary outcome includes all-cause mortality and hospitalization for worsening HF. In this article, we focus on various therapeutic options for the treatment of CSA/HCSB and, when appropriate, emphasize the importance of identifying CSA/HCSB phenotypes to tailor treatment.

In addition to affecting the oxygen supply to the brain, pulmonary function is a marker of multiple insults throughout life (including smoking, illness, and socioeconomic deprivation). In this meta-analysis of existing longitudinal studies, the hypothesis that lower pulmonary function and respiratory illness are linked to an elevated risk of dementia was tested.

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.

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.

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.

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.

Mortality has long been used as a primary end point for randomized controlled trials in critical care. Recently, a plurality of trials targeting mortality end points as their primary outcome has failed to detect a difference between study arms. While there are a number of reasons for the preponderance of such neutral trials, the use of mortality as an outcome is one important consideration. We explore some of the reasons why such trials may be biased toward a neutral result, as well as reasons to consider alternative end points that are better coupled to the expected therapeutic effect. We also discuss to what extent mortality as a binary outcome is patient-important in the ICU.

As the population ages, and more patients with chronic pulmonary diseases become frail and functionally impaired, the prevalence of homebound patients grows. Homebound patients have higher disease burden, inpatient utilization rates, and mortality than nonhomebound patients. Vulnerable homebound patients with pulmonary disease benefit from pulmonary expertise to evaluate and optimize their complex medication regimens; evaluate equipment such as nebulizers, home oxygen, ventilators, and suction machines; and coordinate services. We review the need and benefits of house calls for these patients, and illustrate these needs with cases. We also explore the logistics of making house calls part of pulmonary practice, including supplies needed, safety in the home, and reimbursement. Reimbursement has grown for house calls, and we review how to bill for visits, advance care planning, and care management that is often required when caring for patients with advanced illness. In addition, house calls can often be beneficial for patients who may be identified as high risk and are part of value-based agreements with payers.

Transbronchial cryobiopsy (TBC) is increasingly recognized as a potential alternative to surgical lung biopsy (SLB) for the diagnosis of interstitial lung disease (ILD). The goal of this analysis was to examine the literature on TBC as it relates to diagnostic utility and safety to provide evidence-based and expert guidance to clinicians.

Chronic lung disease accounts for a significant global burden with respect to death, disability, and health-care costs. Due to the heterogeneous nature and limited treatment options for these diseases, it is imperative that the cellular and molecular mechanisms underlying the disease pathophysiology are further understood. The lung is a complex organ with a diverse cell population, and each cell type will likely have different roles in disease initiation, progression, and resolution. The effectiveness of a given therapeutic agent may depend on the net effect on each of these cell types. Over the past decade, it has been established that endoplasmic reticulum stress and the unfolded protein response are involved in the development of several chronic lung diseases. These conserved cellular pathways are important for maintaining cellular proteostasis, but their aberrant activation can result in pathology. This review discusses the current understanding of endoplasmic reticulum stress and the unfolded protein response at the cellular level in the development and progression of various chronic lung diseases. We highlight the need for increased understanding of the specific cellular contributions of unfolded protein response activation to these pathologies and suggest that the development of cell-specific targeted therapies is likely required to further decrease disease progression and to promote resolution of chronic lung disease.

Treatment of pulmonary arterial hypertension (PAH) has evolved substantially over the past two decades and varies according to etiology, functional class (FC), hemodynamic parameters, and other clinical factors. Current guidelines do not provide definitive recommendations regarding the use of oral prostacyclin pathway agents (PPAs) in PAH. To provide guidance on the use of these agents, an expert panel was convened to develop consensus statements for the initiation of oral PPAs in adults with PAH.

Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results.