Long-term macrolide therapy offers an evidence-based treatment to reduce frequent exacerbations in stable adult patients with bronchiectasis. There is limited evidence that these agents also attenuate the decline in lung function and improve health-related quality of life. The benefits and risks of long-term macrolide use need to be clearly explored for individual patients. Further work is needed to understand the optimal drug, dose, and regimen, the mechanisms behind these benefits, appropriate patient selection, sustainability of efficacy, potential long-term risk for the lung microbiome; and their use with or without inhaled antibiotic treatment. We reviewed the current evidence on long-term macrolides in adults with bronchiectasis.

Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.

Fluid challenge may help in the differential diagnosis between pre- and postcapillary pulmonary hypertension (PH). However, the test is still in need of standardization and better defined clinical relevance.

Ultrasonography is an essential imaging modality in the ICU used to diagnose and guide the treatment of cardiopulmonary failure. Critical care ultrasonography requires that all image acquisition, image interpretation, and clinical applications of ultrasonography are personally performed by the critical care clinician at the point of care and that the information obtained is combined with the history, physical, and laboratory information. Point-of-care ultrasonography is often compartmentalized such that the clinician will focus on one body system while performing the critical care ultrasonography examination. We suggest a change from this compartmentalized approach to a systematic whole-body ultrasonography approach. The standard whole-body ultrasonography examination includes thoracic, cardiac, limited abdominal, and an evaluation for DVT. Other elements of ultrasonography are used when clinically indicated. Each of these elements is reviewed in this article and are accompanied by a link to pertinent cases from the Ultrasound Corner section of CHEST.

OSA is associated with increased cancer incidence and mortality. Exosomes are vesicles secreted by most cells. They are released into the bloodstream and play a role in tumor progression and metastasis. We evaluated whether the chronic intermittent hypoxia (IH) that characterizes OSA leads to release of tumor-promoting exosomes in the circulation.

There is a growing use of procalcitonin (PCT) to facilitate the diagnosis and management of severe sepsis. We investigated the impact of one to two PCT determinations on ICU day 1 on health-care utilization and cost in a large research database.

In recent years, numerous studies have generated data supporting the hypothesis that extracellular adenosine 5'-triphosphate (ATP) plays a major role in obstructive airway diseases. Studies in animal models and human subjects have shown that increased amounts of extracellular ATP are found in the lungs of patients with COPD and asthma and that ATP has effects on multiple cell types in the lungs, resulting in increased inflammation, induction of bronchoconstriction, and cough. These effects of ATP are mediated by cell surface P2 purinergic receptors and involve other endogenous inflammatory agents. Recent clinical trials reported promising treatment with P2X3R antagonists for the alleviation of chronic cough. The purpose of this review was to describe these studies and outline some of the remaining questions, as well as the potential clinical implications, associated with the pharmacologic manipulation of ATP signaling in the lungs.

Obesity is prevalent in the United States; however, the impact of obesity on COPD morbidity is unclear. We hypothesized that obesity is associated with worse outcomes in COPD.

Lung cancer screening recommendations have been developed, but none are focused on veterans. We report the results of the lung cancer screening program at our Veterans Affairs medical center and compare them with historic results.

Long-acting bronchodilators, including long-acting beta2-agonists (LABA) and the anticholinergic tiotropium, are recommended as initial maintenance therapy in COPD. Studies to date have been limited in size and reported ambivalent results on the comparative risk of cardiovascular, cerebrovascular, and pulmonary adverse events between these two long-acting bronchodilators. Moreover, little information is available for the period when treatment is first initiated, a time when subjects may be especially at risk.

Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exact pathophysiologic mechanisms and full clinical significance remain uncertain. Treatment of PH related to DPLD remains investigational, but an area of great interest given the negative prognostic implications and the growing number of available pulmonary vasoactive agents.

Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension. The aim of the study was to evaluate the incremental prognostic value of echocardiography of the right ventricle and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients.

Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography (EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL) and healthy never-smokers.

Patients with COPD experience episodes of increased inflammation, so-called acute exacerbations of COPD (AE-COPD). In 30% of AE-COPD cases, no clear cause is found. Since there is well-known cross talk between inflammation and thrombosis, the objectives of this study were to determine the prevalence, embolus localization, clinical relevance, and clinical markers of pulmonary embolism (PE) in unexplained AE-COPD.

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy.

Among the interstitial lung diseases (ILDs), idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis, and fibrotic connective tissue disease-related ILD are associated with a worse prognosis, with death occurring as a result of both respiratory failure and serious associated comorbidities. The recent development and approval of the antifibrotic agents nintedanib and pirfenidone, both of which reduced the rate of decline in lung function in patients with IPF in clinical trials, offer hope that it may be possible to alter the increased mortality associated with IPF. Although chronic hypersensitivity pneumonitis and connective tissue disease related-ILD may be associated with an inflammatory component, the evidence for the use of immunosuppressive agents in their treatment is largely limited to retrospective studies. The lack of benefit of immunosuppressive therapy in advanced fibrosis argues for rigorous clinical trials using antifibrotic therapies in these types of ILD as well. Patients with fibrotic ILD may benefit from identification and management of associated comorbid conditions such as pulmonary hypertension, gastroesophageal reflux, and OSA, which may improve the quality of life and, in some cases, survival in affected individuals. Because early assessment may optimize posttransplantation outcomes, lung transplant evaluation should occur early in patients with IPF and those with other forms of fibrotic ILD.

Lung cancer screening using low-dose CT scanning reduces lung-cancer-specific and overall mortality in high-risk patients. A significant limitation of lung cancer screening is the false-positive rate. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) was designed to standardize reporting of low-dose lung cancer screening results and to decrease the false-positive rate without significantly compromising sensitivity. Implementing Lung-RADS can also improve cost-effectiveness. However, Lung-RADS has never been studied in a prospective fashion. It also does not have a specific reporting category for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules. We report four such cases from our lung cancer screening program. We believe that this is a significant limitation of Lung-RADS and should be revised in its new version.

The incidence of pleural infection has been rising in recent years. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has significantly reduced the need for surgery, and its impact on clinical care is rising worldwide. Efforts are underway to optimize the delivery regimen and establish the short and longer term effects of this therapy. The complex interactions of bacterial infection within the pleura with inflammatory responses and clinical interventions (antibiotics and tPA/DNase or other fibrinolysins) require further studies to improve future treatment options. Intrapleural instillation of tPA potently induces pleural fluid formation, principally via a monocyte chemotactic protein (MCP)-1 dependent mechanism. Activation of transcriptional programs in pleural resident cells and infiltrating cells during pleural infection and malignancy results in the local secretion of a cocktail of proinflammatory signaling molecules (including MCP-1) within the pleural confines that contributes to effusion formation. Understanding the biology of these molecules and their interaction may provide novel targets for pleural fluid control.

In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected.