The number of pharmacological medications available to treat patients with COPD has increased over the past few decades. Most of the improvement has come from the modification of older compounds that are now more potent, of longer duration, and delivered in improved devices. They are now available as single, double, and even triple combinations that, although attempting to simplify administration, have also resulted in a large number of preparations. These medications are clearly effective and should be used as a central component of the multidimensional approach to the patient affected with COPD. The preferred route remains the inhaled direct delivery to the airways, but the favorable results obtained with systemic agents such as macrolides and roflumilast and the preliminary results of some biologicals are opening the door for the development of new drugs or reformulation of medications that have been used for other indications. Perhaps the most pressing need is to study the effect of these agents at early points in the course of the disease, because until now most, if not all, studies have been conducted in patients usually older than age 60 years, when most of the natural course of the disease has already been run. This monograph reviews the available pharmacological therapy based on current evidence and provides practical recommendations to health providers caring for patients with COPD.

COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD.

Treatment of hepatic hydrothorax (HH) generally involves sodium restriction, diuretics, and serial thoracentesis. In more advanced cases, transjugular intrahepatic portosystemic shunt and liver transplantation may be required. Previously, indwelling tube drainage has been avoided due to concerns regarding high complication rates and overall poor outcomes. Recently, indwelling pleural catheters (IPCs) have been proposed as a novel treatment option for HH.

Amyotrophic lateral sclerosis is a progressive neuromuscular disease characterized by both lower motor neuron and upper motor neuron dysfunction. Although clinical presentations can vary, there is no cure for ALS, and the disease is universally terminal, with most patients dying of respiratory complications. Patients die, on average, within 3 to 5 years of diagnosis, unless they choose to undergo tracheostomy, in which case, they may live, on average, 2 additional years. Up to 95% of patients with ALS in the United States choose not to undergo tracheostomy; management of respiratory failure is therefore aimed at both prolonging survival as well as improving quality of life. Standard of care for patients with ALS includes treatment from multidisciplinary teams, but many patients do not have consistent access to a pulmonary physician who regularly sees patients with this disease. The goal of this review was to serve as an overview of respiratory considerations in the management of ALS. This article discusses noninvasive ventilation in the management of respiratory muscle weakness, mechanical insufflation/exsufflation devices for airway clearance, and treatment of aspiration, including timing of placement of a percutaneous endoscopic gastrostomy tube, as well as secretion management. In addition, it is important for physicians to consider end-of-life issues such as advanced directives, hospice referral, and ventilator withdrawal.

Noncystic fibrosis bronchiectasis (bronchiectasis) is an increasingly common chronic lung disease that is difficult to manage because of a lack of evidence on which to base treatment decision-making. We sought to develop a practical list of US-based patient-centered research priorities and an associated roadmap to guide bronchiectasis research. We designed and administered a web-based patient needs assessment survey to establish broad research priorities, convened three stakeholder webinars to confirm the top priorities, obtained written stakeholder feedback, and completed a final consensus survey of objectives. The stakeholder panel consisted of clinical research experts in bronchiectasis, a seven-member patient advisory panel, and representatives from the two key patient advocacy organizations: COPD Foundation and NTM Info and Research Inc. Based on survey results from 459 patients with bronchiectasis, the stakeholder panel identified 27 patient-centered research priorities for bronchiectasis in the areas of bronchiectasis treatment and prevention of exacerbations, improving treatment of exacerbations and infections, improving health-related quality of life, predictors of poor prognosis, understanding the impact of underlying conditions, and conducting patient-centered clinical trials. These priorities should further inform the development and evaluation of both new and previously unproven therapies, with particular attention to the inclusion of patient-reported outcomes. We anticipate a great deal of progress will be made in the field of bronchiectasis in the next decade.

As the cost of health care continues to escalate, payers are adapting by moving away from models based on traditional fee-for-service reimbursement to models focused on rewarding care delivery that reduces costs and improves quality. These alternative payment models (APMs) are being introduced by government and commercial payers and will likely become the norm over time. Recent changes in sleep medicine related to advances in technology and approaches by payers for the management of OSA make this an appropriate time to incorporate the delivery of sleep medicine services into APMs. For OSA, the approaches that should lead to success include the appropriate use of home sleep apnea testing and automatic positive airway pressure; lower cost providers to manage less complex patients; evolving technologies including cloud-based positive airway pressure adherence monitoring, telemedicine, and Internet-based coaching to improve adherence with treatments; data analytics to better identify high-risk populations and to more appropriately allocate resources; and appropriate referrals of more complex cases to sleep specialists for management. All of these approaches should improve the value of care for payers, providers, and patients while allowing sleep specialists to more appropriately allocate their efforts to overseeing APM program development and administration and allowing them to focus on the management of more complicated patients.

The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (α1 chain, C4M2), and type IV (α3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-C5) were investigated and associated with COPD severity and outcome.

The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an expected median survival of 3 months. Lung transplantation is a potentially lifesaving therapy for AE-IPF. However, the current knowledge of transplantation outcomes during AE-IPF is limited to a few small retrospective studies, reporting only 1-year post-transplantation survival.

Since their introduction into health care and clinical practice in the early 20th century, antibiotics have revolutionized medicine. Alarmingly, these drugs are increasingly threatened by bacteria that have developed a broad diversity of resistance mechanisms. Antibiotic resistance can be transferred between bacteria, often on mobile genetic elements; be acquired from the environment; or arise through mutation because of selective pressures of the drugs themselves. There are various strategies to resistance, including active efflux of the drug from the bacterial cell, reduced permeability of the cell envelope, alteration of the drug's target within the bacterial cell, and modification or destruction of the antibiotic. Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis frequently are implicated in respiratory infections, often manifesting with reduced susceptibility to multiple classes of antibiotics. Some mechanisms of resistance, such as the β-lactamases that confer resistance to penicillins and related drugs, have been well characterized and are widespread in clinical isolates. Other newly identified determinants, including the colistin resistance gene mcr-1, are spreading rapidly worldwide and threaten last-resort treatments of multidrug-resistant organisms. Various approaches to detecting antibiotic resistance provide surveys of the determinants that are available for transfer into pathogenic bacteria. Together with molecular characterization of newly identified mechanisms, this surveillance can target drug discovery efforts and increase antibiotic stewardship. A greater understanding of the mechanisms of antibiotic resistance in respiratory pathogens combined with rapid diagnostics ultimately will reduce treatment failure due to inappropriate antibiotic use and prevent further spread of resistance.

The natural history of lymphangioleiomyomatosis (LAM) is mainly derived from retrospective cohort analyses, and it remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM.

The role of decreased pulmonary arterial (PA) compliance (C), equivalent to increased PA stiffness (1/C), as a critical determinant of right ventricular dysfunction and prognosis has been emphasized in pulmonary arterial hypertension (PAH).

Tumor spread through air spaces (STAS) has recently been reported as a novel form of lung adenocarcinoma invasion that can negatively affect survival; however, its role in pleomorphic carcinoma remains unclear. The goal of this study was to characterize tumor STAS in pleomorphic carcinoma, including its association with clinicopathologic features and prognosis.

The effect of ICU telemedicine on transfers is not well studied. This study tests the hypothesis that ICU telemedicine decreases ICU patient interhospital transfers.

Patients with COPD may experience acute mountain sickness (AMS) and other altitude-related adverse health effects (ARAHE) when traveling to high altitudes. This study evaluated whether dexamethasone, a drug used for the prevention of AMS in healthy individuals, would prevent AMS/ARAHE in patients with COPD.

To improve the delivery of patient care, governments and health-care institutions adopted quality improvement methods that had been developed decades earlier in manufacturing industries. Many health-care practitioners are either unaware or are inexperienced about what these practices entail and whether they are successful in health care. This article reviews Lean, an improvement philosophy made famous by the Toyota Motor Company. Lean uses a set of instruments and incorporates a long-term vision aiming for continuous improvement. It focuses on eliminating waste as perceived by the patient, thereby maximizing quality and safety for the patient. However, the effort required for the attainment of Lean's goals is often not appreciated. Indeed, successful and sustainable implementation requires immense institutional culture change combined with innovative leadership and motivated frontline health-care professionals.

Paradoxically, the vast majority of research models intended to understand the relationship between exogenous exposures and lung disease are reduced to a single inhalant. This approach is understandable given the practical challenges of investigation, but it is problematic in terms of translation to the real-world human condition. Furthermore, use of data from such models can lead to underestimation of effect, which may adversely influence regulatory imperatives to protect public health based on the most robust information. Efforts to incrementally introduce layers of complexity to observational and experimental systems have revealed pathophysiology previously "hidden" within simplified models. Capturing the effects of co-exposure to traffic-related air pollution and allergens is a paradigmatic example and illustrates the influence of co-exposures across a plethora of clinical and subclinical end points within the respiratory tract. From DNA methylation in the epithelium, to inflammatory mediators and allergen-specific antibodies in the airway, to airflow limitation and symptoms, the addition of a common second exposure induces profound changes. In addition, genetic variation significantly alters the product of these relationships, and capturing multidimensional interactions may reveal susceptible populations who are particularly affected by these exposures and may merit focused measures for protection. Collectively, better modeling, and ultimately deeper knowledge, of these complex relationships has important implications for personalized health and prevention, development and refinement of pharmacologic agents, and public health responses to climate change and the staggering burden of pollution-driven disease worldwide.

Several clinical trials have shown the efficacy of continuous infusion beta-lactam (BL) antibiotics in patients with cystic fibrosis (CF); however, little is known about pharmacokinetic changes during the treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment.

Single omic analyses have provided some insight into the basis of lung function in children with asthma, but the underlying biologic pathways are still poorly understood.

Viral pathogens are a common cause of severe lower respiratory tract infection in adults. Our ability to rapidly and accurately identify viral infections has dramatically improved as slow culture-based techniques have been largely replaced by multiplex high-throughput systems. Given these advances, reevaluation of the role of respiratory viral testing in adults presenting with lower respiratory tract infection is important. This article reviews the potential benefits of testing, provides an overview of the most commonly used diagnostic techniques, and considers whether current evidence supports routine testing.