Long-term dyspnea and exercise intolerance are common clinical problems after acute pulmonary embolism. Unfortunately, no single test can distinguish among the range of potential pathologic outcomes after pulmonary embolism. We illustrate a stepwise approach to post-pulmonary embolism evaluation that uses a hierarchic series of clinically validated diagnostic tests. The algorithm is represented by the acronym SEARCH, which stands for Symptom screening, Exercise testing, Arterial perfusion, Resting echocardiography, Confirmatory chest imaging, and Hemodynamics measured by right heart catheterization. We illustrate the algorithm with a patient whom we saw in our pulmonary embolism follow-up clinic. Patients are asked at least 6 months after pulmonary embolism whether they have returned to their baseline level of respiratory comfort and exercise tolerance. Patients with dyspnea and exercise intolerance undergo noninvasive cardiopulmonary exercise testing to identify elevated ventilatory dead space ratios, decreased stroke volume augmentation with exercise, and other physiologic abnormalities during exertion. Ventilation-perfusion scanning is performed on those patients with exercise-related physiologic findings to confirm the presence of residual pulmonary arterial obstruction or to suggest alternative diagnoses. Resting echocardiography may provide evidence of pulmonary hypertension; confirmatory imaging with pulmonary angiography or CT angiography may disclose findings characteristic of chronic pulmonary artery obstruction. Finally, right heart catheterization is performed to confirm chronic thromboembolic pulmonary hypertension; if resting pulmonary hemodynamics are normal, then invasive cardiopulmonary exercise testing may disclose exercise-induced defects.

Advances in our understanding of interstitial lung disease (ILD) pathophysiology and natural history have led to the development of guidelines for the diagnosis and management of several of these complex diseases. The demographics of patients with ILD indicate the disease is not restricted to older adults. Connective tissue disease-associated ILD, familial pulmonary fibrosis, and post-COVID-19 fibrosis may affect women of child-bearing age. Recent trials have excluded pregnant women, thereby limiting the applicability of contemporary therapeutic advances to these patients. This review synthesizes the current knowledge of pregnancy outcomes in those with ILD, with a focus on connective tissue disease-associated ILD, and potential treatment implications for patients with ILD who are pregnant or considering pregnancy. Pregnancy considerations for patients with ILD include the need for preconception counseling and planning to ensure disease stability, medication and vaccination optimization, and multidisciplinary involvement of a patient's pulmonologist, obstetrician, and, when indicated, rheumatologist and genetic counselor. Evidence to date suggests that women with ILD can have safe and healthy pregnancies but that complications may occur in those with severe ILD.

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.

Chylothorax, the accumulation of chyle in the pleural space, is usually caused by the disruption of the thoracic duct or its tributaries. Etiologies are broadly divided into traumatic, including postsurgical, and nontraumatic, most commonly in the setting of malignancy. The management of chylothorax largely depends on the cause and includes dietary modification and drainage of the pleural space. A definitive intervention, whether surgical or a percutaneous lymphatic intervention, should be considered in patients with a persistently high volume of chylous output and in those with a prolonged leak, before complications such as malnutrition ensue. No methodologically robust clinical trials guiding management are currently available. In this article, we review the current literature and propose a stepwise, evidence-based multidisciplinary approach to the management of patients with both traumatic and nontraumatic chylothorax.

Professionalism in health care occurs in environments that present complex ethical dilemmas that demand ideal individual and team performance. Clinicians who behave unprofessionally toward patients and family members create a disproportionate share of risk for adverse patient outcomes and malpractice claims. However, when made aware, the vast majority will self-regulate. Several options exist for a clinician who observes or hears about an interaction between a colleague and a patient or family member that does not seem to be consistent with the organization's commitment to treat individuals with respect and dignity. Responses to unprofessional behavior need to recognize and balance the rights and responsibilities of key stakeholders, including patients, clinicians, coworkers, and the organization. In one approach, the clinician would speak directly with the colleague to make them aware of the event and encourage them to consider alternative approaches in future similar interactions. Alternatively, the clinician could ensure that the story is reported, reviewed, and shared through the organization's professional accountability program. Professional accountability programs must be supported by appropriate infrastructure elements. Sharing the observation helps to address the concerns and fears of patients and family members, offers a colleague the chance to reflect and reduce the likelihood of future unprofessional behavior, and seeks to fulfill one's individual responsibility to support colleagues as professionals, while striking the right balance of dignity, respect, and pursuit of trust for all key stakeholders.

Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce.

Indeterminate randomized controlled trials (RCTs) in ARDS may arise from sample size misspecification, leading to abandonment of efficacious therapies.

Restless legs syndrome (RLS) is a sensory-motor neurologic disorder present to a clinically significant degree in 2% to 3% of the adult population, more commonly with advancing age and in women, that dramatically affects sleep and quality of life. Addressing factors that worsen RLS (eg, iron deficiency, antidepressant or antihistamine administration, OSA) is an important first step in treatment. RLS can generally be well treated with medications such as the alpha2-delta calcium channel ligands (A2Ds) gabapentin, pregabalin, and gabapentin enacarbil or, if these are poorly tolerated or lack efficacy, the dopamine agonists (DAs) pramipexole, ropinirole, or rotigotine. Oral or IV iron supplementation is often efficacious as initial treatment in patients with low normal serum indexes. However, at least one-third of patients do not achieve acceptable symptom relief from initial treatments. Furthermore, DAs, the most commonly used medications for RLS, commonly produce augmentation, a progressive, long-term, iatrogenic worsening of RLS symptoms characterized by increasing severity as well as temporal and anatomic extension of symptoms. If dopaminergic augmentation of RLS is present, substitution of an A2D or opioid for the DA is the primary goal. However, given the profound rebound RLS and insomnia that occurs with even small dose reductions of DAs, the initial change should be the addition of one of these alternate treatments. Once adequate doses, or symptom relief, are achieved with the second agent, subsequent very slow down-titration and discontinuation of the DA is often possible and can lead to dramatic long-term relief of RLS symptoms and improvement in sleep.

Sleep disturbances are often cited as a primary reason for medicinal cannabis use, and there is increasing clinical interest in the therapeutic potential of cannabinoids in treating sleep disorders. Burgeoning evidence suggests a role of the endocannabinoid system in regulating the circadian sleep-wake cycle, highlighting a potential avenue for developing novel therapeutics. Despite widespread use of cannabis products as sleep aids globally, robustly designed studies verifying efficacy in sleep-disordered populations are limited. Although some study outcomes have suggested cannabinoid utility in insomnia disorder and sleep apnea, most studies to date are limited by small sample sizes, lack of rigorously controlled study designs, and high risk of bias. This critical review summarizes the current evidence for the use of cannabinoids as a treatment for sleep disorders and provides an overview of endocannabinoid modulation of sleep-wake cycles, as well as the sleep-modulating effects of plant-derived cannabinoids such as delta-9-tetrahydrocannbinol, cannabidiol, and cannabinol. The review also discusses practical considerations for clinicians regarding cannabinoid formulations, routes of administration, respiratory concerns, dosing, potential side effects, drug interactions, and effects relevant to driving, tolerance, and withdrawal. Although current interest in, and uptake of, medicinal cannabis use for sleep disorders may have surpassed the evidence base, there is a strong rationale for continued investigation into the therapeutic potential of cannabinoids.

Mortality historically has been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome, and focusing solely on mortality fails to recognize the importance that reducing morbidity can have on patients' lives. The COVID-19 pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury: mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs typically is greater than that for other clinical trial outcomes, such as mortality and ventilator-free days. OFDs is the primary outcome for the Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This article outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

Accurate assessment of maximum respiratory pressure is vital when tracking disease progression and devising treatment strategies. Previous studies indicate a learning effect when undertaking maximum respiratory pressure measurements. The extent of this learning effect and methodologies undertaken to mitigate this learning effect have not been investigated systematically.

The current approach to interpretation of lung function measurements assumes that differences in lung function between racial and ethnic groups represent inherent and biological differences. Observed differences in lung function between White and Black populations are often attributed to physiological differences in body proportions (eg, chest size, leg length); however, most studies investigating the observed differences have not considered the impact of socioeconomic status (SES).

In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacologic treatment of mechanical abnormalities in COPD (eg, bronchodilators to deflate the lungs), increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD, may be explained by an increased venous admixture resulting from low V˙A/Q˙c, or wasted ventilation related to high V˙A/Q˙c, or both. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance that act primarily on V˙A (bronchodilators, antiinflammatory medications) or Q˙c (oral and inhaled vasodilators, almitrine, and supplemental oxygen). Finally, to address the current knowledge and health care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange inefficiency and activity-related dyspnea in COPD: (1) enhanced and deeper phenotyping of patients with COPD with V˙A/Q˙c abnormalities and (2) evaluation of existing and novel pharmacologic treatments to improve gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity.

Patients with familial pulmonary fibrosis represent a subset of patients with pulmonary fibrosis in whom inherited gene variation predisposes them to disease development. In the appropriate setting, genetic testing allows for personalized assessment of disease, recognition of clinically relevant extrapulmonary manifestations, and assessing susceptibility in unaffected relatives. However currently, the use of genetic testing is inconsistent, partly because of the lack of guidance regarding high-yield scenarios in which the results of genetic testing can inform clinical decision-making. To address this, the Pulmonary Fibrosis Foundation commissioned a genetic testing work group comprising pulmonologists, geneticists, and genetic counselors from the United States to provide guidance on genetic testing in patients with pulmonary fibrosis. This CHEST special feature presents a concise review of these proceedings and reviews pulmonary fibrosis susceptibility, clinically available genetic testing methods, and clinical scenarios in which genetic testing should be considered.

The outbreak of COVID-19 has brought renewed attention to past narratives of disease outbreaks. What do the Black Death and COVID-19 have in common? How we tell outbreak stories is shaped by political, cultural, social, and historical contexts. It is deeply rhetorical. The general public relies on experts (scientists, historians, and government officials) to provide credible information, but uncertainties during an outbreak can make it difficult to provide definitive answers quickly. Experts need to be conscious about the contexts in which their statements would be received. Regarding the Black Death, historians of medicine have relied heavily on a single medieval account of the outbreak, which confirmed their preconceptions about Mongol violence, allowing them to present the Black Death as an instance of biological warfare. Looking at other medieval accounts, however, makes clear that this narrative of Mongol biological warfare is false. Similarly, modern outbreak narratives also tend to use militarized language, which results in othering peoples and cultures where a disease might have originated. Given the contemporary political tensions between China and the United States, narratives about the origin of the SARS-CoV-2 virus and its transmission have led to a transnational infodemic of misinformation as well as discrimination and violence against people of Asian descent. In light of this long-running pattern, we argue for more interdisciplinary collaborations between the experts whose work is used to build outbreak narratives to adopt more critical rhetorical approaches in communicating with the public.

The terms sex and gender often are used interchangeably, but have specific meaning when it comes to their effects on lung disease. Ample evidence is now available that sex and gender affect the incidence, susceptibility, presentation, diagnosis, and severity of many lung diseases. Some conditions are more prevalent in women, such as asthma. Other conditions are seen almost exclusively in women, like lymphangioleiomyomatosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as higher number of exacerbations experienced by women with COPD and greater cardiovascular morbidity in women with sleep-disordered breathing. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors often are not addressed adequately in clinical trials. Various aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for women. This article is a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of lung diseases. Pathobiological mechanisms explaining sex differences in these diseases are beyond the scope of this article. We review the literature and focus on recent guidelines about using sex and gender in research. We also review sex and gender differences in lung diseases.

In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU.

Obesity is increasingly prevalent in pulmonary arterial hypertension (PAH) but is associated with improved survival, creating an "obesity paradox" in PAH. It is unknown if the improved outcomes could be attributable to obese patients deriving a greater benefit from PAH therapies.

Asthma exacerbations can be life-threatening, with 25,000 to 50,000 such patients per year requiring admission to an ICU in the United States. Appropriate triage of life-threatening asthma is dependent on both static assessment of airway function and dynamic assessment of response to therapy. Treatment strategies focus on achieving effective bronchodilation with inhaled β2-agonists, muscarinic antagonists, and magnesium sulphate while reducing inflammation with systemic corticosteroids. Correction of hypoxemia and hypercapnia, a key in managing life-threatening asthma, occasionally requires the incorporation of noninvasive mechanical ventilation to decrease the work of breathing. Endotracheal intubation and mechanical ventilation should not be delayed if clinical improvement is not achieved with conservative therapies. However, mechanical ventilation in these patients often requires controlled hypoventilation, adequate sedation, and occasional use of muscle relaxation to avoid dynamic hyperinflation, which can result in barotrauma or volutrauma. Sedation with ketamine or propofol is preferred because of their potential bronchodilation properties. In this review, we outline strategies for the assessment and management of patients with acute life-threatening asthma focusing on those requiring admission to the ICU.

Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification.