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The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.

Different ages of asthma onset can lead to similar clinical symptoms but have different underlying mechanisms that may influence treatment response. This post-hoc analysis assessed response to omalizumab in relation to the age of asthma onset. Using pooled data from two phase III studies (patients 12–75 years), changes in exacerbation rates, forced expiratory volume in 1 second (FEV1) and inhaled corticosteroids (ICS) were assessed by age of asthma onset (40 years [ n = 136]). Exacerbations (week 16) were reduced with omalizumab versus placebo in all subgroups (relative rate reduction [95% confidence interval]: 40, −38.4% [–77.3,67.4]). FEV1 increased with omalizumab in all subgroups; increases were sustained in 40 years subgroup. ICS dose reductions (week 28) were greater with omalizumab versus placebo, regardless of age of asthma onset, as were percentages of patients with ICS doses reduced by at least 50% and 100%. In conclusion, omalizumab-treated patients had lower exacerbation rates and were more frequently able to reduce/discontinue ICS versus placebo, regardless of age of asthma onset, therefore omalizumab may be beneficial to all eligible patients with allergic asthma. Trial registration These studies were conducted before clinical trial registration was required; therefore, clinical trial registration numbers are not available.

Hospitalized patients with asthma and/or chronic obstructive pulmonary disease have a chronic inflammatory disease of the lungs that can be successfully managed with timely identification, evaluation, and medical treatment to prevent and treat exacerbations. If possible, an experienced interdisciplinary team led by hospitalists who are involved early in the hospitalization is more likely to achieve shorter hospital lengths of stay, improve regular outpatient follow-up, and reduce rates of hospital readmission for exacerbations.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD—with a focus on comorbid cardiovascular disease.

Asthma is a complex inflammatory disease with many triggers. The best understood asthma inflammatory pathways involve signals characterized by peripheral eosinophilia and elevated immunoglobulin E levels (called T2-high or allergic asthma), though other asthma phenotypes exist (eg, T2-low or non-allergic asthma, eosinophilic or neutrophilic-predominant). Common triggers that lead to poor asthma control and exacerbations include respiratory viruses, aeroallergens, house dust, molds, and other organic and inorganic substances. Increasingly recognized non-allergen triggers include tobacco smoke, small particulate matter (eg, PM2.5), and volatile organic compounds. The interaction between respiratory viruses and non-allergen asthma triggers is not well understood, though it is likely a connection exists which may lead to asthma development and/or exacerbations. In this paper we describe common respiratory viruses and non-allergen triggers associated with asthma. In addition, we aim to show the possible interactions, and potential synergy, between viruses and non-allergen triggers. Finally, we introduce a new clinical approach that collects exhaled breath condensates to identify metabolomics associated with viruses and non-allergen triggers that may promote the early management of asthma symptoms.

Bronchial thermoplasty (BT) delivers targeted radiofrequency energy to bronchial airway walls and results in the partial ablation of the airway smooth muscle that is responsible for bronchoconstriction. It is approved for the treatment of severe persistent asthma. Multiple, large clinical trials including a recent "real-world" study demonstrate significant improvements in asthma-related quality of life, reduction in asthma exacerbations, emergency department visits, and hospitalizations after BT that is sustained out to 5 years. In this article, we review the state of the art of BT treatment in severe persistent asthma and share a decade of BT research and clinical experience. We share our personal experience and introduce the three "I"s (identification, implementation, and intense follow-up) that we believe promote successful patient outcomes and help build a successful BT program.

The elderly patient (65 years and older) with chronic obstructive pulmonary disease (COPD) can be a challenge to the clinician. This begins with the correct and early diagnosis, the assessment of disease severity, recognizing complicating comorbidities, determining the burden of symptoms, and monitoring the frequency of acute exacerbations. Comprehensive management of COPD in the elderly patient should improve health-related quality of life, lung function, reduce exacerbations, and promote patient compliance with treatment plans. Only smoking cessation and oxygen therapy in COPD patients with hypoxemia reduce mortality. Bronchodilators, corticosteroids, methylxanthines, phosphodiesterase-4 inhibitors, macrolide antibiotics, mucolytics, and pulmonary rehabilitation improve some outcome measures such as spirometry measures and the frequency of COPD exacerbations without improving mortality. International treatment guidelines to reduce symptoms and reduce the risk of acute exacerbations exist. Relief of dyspnea and control of anxiety are important. The approach to each patient is best individualized. Earlier use of palliative care should be considered when traditional pharmacotherapy fails to achieve outcome measures and before consideration of end-of-life issues.

Laren D Tan,1 Nicholas Kenyon,2 Ken Y Yoneda,2 Samuel Louie2 1Division of Pulmonary, Critical Care, Hyperbaric and Sleep Medicine, Department of Internal Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 2Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, USA Abstract: Increasing dependence on advanced technologies in the 21st century has created a dilemma between the practice and business of medicine. From information technology to robotic surgery, new technologies have expanded treatment possibilities and have potentially improved patient outcomes and safety. Simultaneously, their escalating costs limit access for certain patients and health care facilities. Nevertheless, medical decisions should not simply be based on cost. Input from physicians and other health care specialists as well as adherence to best practice position statements, are vital to implementing truly cost-effective strategies in medicine. Bronchial thermoplasty (BT), a US Food and Drug Administration approved bronchoscopy procedure in difficult-to-control persistent asthma, is a prime example of a new technology facing cost and implementation challenges. We discuss the specific indications and contraindications for BT and review recent real-world experiences that can provide the foundation for building a comprehensive asthma program that provides BT for difficult-to-control asthma patients who fail national guideline treatment recommendations after an adequate clinical trial of one. We also offer insight into the barriers to implementing a successful BT program and strategies for overcoming them. Keywords: asthma, severe asthma, severe refractory asthma, biologic resistant asthma, BT

BackgroundGastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure.Case presentationOur patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting β2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting.ConclusionsLINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

Idiopathic pulmonary fibrosis (IPF) is a disease of the elderly with a mean age at presentation of 66 years. It is the most common type of idiopathic lung fibrosis, and the most lethal, with a median survival of 3 to 5 years after diagnosis. Abnormalities in fibroblast and humoral response mechanisms may play a role in the pathogenesis of fibrosis in IPF. Clinical trials suggest that pirfenidone, an oral antifibrotic agent, N-acetylcysteine, an antioxidant and perhaps anticoagulation, may have some beneficial effect; however, large-scale studies are necessary for confirmation. Immunosuppression with corticosteroids likely does not confer benefit. Lung transplantation has been shown to improve survival in selected IPF patients. Comorbidities accompanying IPF include gastroesophageal reflux, sleep disturbance, pulmonary arterial hypertension, and coronary artery disease amongst others, and ought to be promptly recognized and managed appropriately. While the US Food and Drug Administration has not currently approved any treatments for IPF, patients with IPF should continue to be strongly encouraged to enroll in ongoing clinical trials for this devastating disease.

Goodpasture’s disease, or anti-glomerular basement membrane (anti-GBM) disease, is a systemic autoimmune disorder defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. It may be regarded as a “conformeropathy” where the quaternary structure of the α345NC1 hexamer that constitutes GBM undergoes a conformational change, exposing pathogenic epitopes on the α3 and α5 chains, eliciting a pathogenic autoantibody anti-GBM response. Goodpasture’s disease accounts for 20% of all patients presenting with a pulmonary-renal syndrome and may be associated with detectable perinuclear antineutrophil cytoplasmic autoantibody positivity in up to a third of patients. Associated triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse. Cough, hemoptysis, and dyspnea with fatigue are the commonest presenting features. It is critical to rapidly distinguish Goodpasture’s disease from other causes of pulmonary-renal syndromes such as Wegener’s granulomatosis. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of Goodpasture’s disease. The need for hemodialysis on initial presentation, a serum creatinine >5 mg/dL, and 50% to 100% crescents on renal biopsy, portend the necessity of long-term hemodialysis. Further elucidation of the molecular pathobiology of Goodpasture’s disease, particularly the regulation of involved antigen-specific T cells, may improve early diagnosis, treatment, and outcomes in this rare but potentially lethal autoimmune disorder.

The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.

Post-translational sulfation of tyrosines affects the affinity and binding of at least some chemokine receptors to their ligand(s) and has been hypothesized to be a feature in all chemokine receptors. This binding initiates downstream signaling cascades. By this mechanism, tyrosine sulfation can influence the cells involved in acute and chronic events of cellular immunity. These events include leukocyte trafficking and airway inflammation important in asthma and chronic obstructive pulmonary disease (COPD). We are using computational methods to convert the poorly defined hypothesis of more widespread sulfation of chemokine receptors to more specific assessments of how closely the sequence environment of each tyrosine residue resembles the sequence environment of tyrosine residues proven to be sulfated. Thus, we provide specific and readily tested hypotheses about the tyrosine residues in all of the chemokine receptors. Tyrosine sulfation was predicted with high scores in the N-terminus domain of 13 out of 18 human chemokine receptor proteins using a position-specific scoring matrix, which was determined to be 94.2% accurate based on Receiver Operating Characteristic analysis. The remaining chemokine receptors have sites exhibiting features of tyrosine sulfation. These putative sites demonstrate clustering in a manner consistent with known tyrosine sulfation sites and conservation both within the chemokine receptor family and across mammalian species. Human chemokine receptors important in asthma and COPD, such as CXCR1, CXCR2, CXCR3, CXCR4, CCR1, CCR2, CCR3, CCR4, CCR5, and CCR8, contain at least one known or predicted tyrosine sulfation site. Recognition that tyrosine sulfation is found in most clinically relevant chemokine receptors could help the development of specific receptor-ligand antagonists to modulate events important in airway diseases.

Palliative care services for patients with chronic obstructive pulmonary disease (COPD) have been limited in most health care schemes despite the significant impact its symptoms can have on quality of life (QOL). Palliative care must be integrated to address physical and emotional distress and QOL deterioration more effectively. Multi-factorial barriers in current health care systems impede the provision of palliative care, including the lack of familiarity among health care professionals. There are sparse evidence-based studies and guidelines for clinicians to better recognize the need for palliative care in COPD patients compared to the large experience and resources available to cancer patients and hospice care. The multidisciplinary approach of palliative care should help COPD patients navigate through the continuum of chronic disease management. Highest QOL, not necessarily the highest physiologic goals, with relief of physical and emotional suffering, are most important to patients. Hospice care, the last phase of palliative care, can be offered to COPD patients when their goal of care has changed from life-prolonging therapies to comfort treatment. We suggest a scheme for identifying COPD patients for palliative care and for delivering simultaneous disease-directed care to help patients live life to the fullest. Pulmonary rehabilitation offers the best venue for incorporating palliative care. We review the need for, barriers to, and key activities for integrating palliative care into the current health care management of patients living with COPD.

© 2016 Tan et al. The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%-10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%-60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy.

Difficult-to-control asthma in adults is under-diagnosed and under-treated in the United States, particularly in those 40 years of age or older. Increasing attention has been focused on the subset of adult patients with poorly controlled asthma because they consume up to 85% of all health care dollars spent on asthma, while representing 20% of all asthma patients. In this article, we define difficult-to-control asthma and discuss the problem of misdiagnosis. We present an algorithm for confirming the diagnosis in these patients and highlight the importance of patient self-assessment.

Post-translational modification of proteins by tyrosine sulfation enhances the affinity of extracellular ligand-receptor interactions important in the immune response and other biological processes in animals. For example, sulfated tyrosines in polyomavirus and varicella-zoster virus may help modulate host cell recognition and facilitate viral attachment and entry. Using a Position-Specific-Scoring-Matrix with an accuracy of 96.43%, we analyzed the possibility of tyrosine sulfation in all 1517 animal viruses available in the Swiss-Prot database. From a total of 97,729 tyrosines, we predicted 5091 sulfated tyrosine sites from 1024 viruses. Our site predictions in hemagglutinin of influenza A, VP4 of rotavirus, and US28 of cytomegalovirus strongly suggest an important link between tyrosine sulfation and viral disease mechanisms. In each of these three viral proteins, we observed highly conserved amino acid sequences surrounding predicted sulfated tyrosine sites. Tyrosine sulfation appears to be much more common in animal viruses than is currently recognized.

The prognosis and response to therapy of metastases to the lungs are variable and highly dependent on the origin of the primary tumor and on the extent and pattern of spread. Due to the complex pathogenesis underlying the development of pulmonary metastases, specific tumor types often display characteristic clinical and radiographic patterns. Understanding these concepts is of paramount importance when planning a diagnostic work-up for patients with possible pulmonary metastases. This review presents state of the art strategies in imaging, medical therapy, and surgery. It should provide the busy pulmonologist with the information needed to devise safe and efficient diagnostic and treatment strategies for patients with pulmonary metastases of extrathoracic origin.

Introduction: Although dyspnea is considered the primary activity-limiting symptom in patients with COPD, other symptoms, such as fatigue, are frequently reported, The purpose of this study was to determine the relationship between fatigue and pulmonary function, exercise tolerance, depression, and qualify of life in patients with COPD. Methods: Forty-one patients (age 62 +/- 8 years; FEV, = 1.08 +/- 0.55 L; FEV1 percent predicted = 35.8 +/- 17%) fi om two sites participated in the study. Spirometric measures of pulmonary function were carried out in each patient. The Multidimensional Fatigue Inventory was used to measure five subscales of fatigue: general, physical and mental fatigue, reduction in activity, and reduction in motivation, The SI. George Respiratory Questionnaire, used to measure quality of life, has three subscale dimensions (symptom, activity, and impact), as well as an overall or total quality of life score. Depression was measured with the Centers of Epidemiological Studies Depression Scale, In 19 patients, exercise tolerance was determined with the 6-min walking distance, Results: General fatigue correlated with FEV1, percent predicted (r = -0.32, p

Critical asthma syndrome represents the most severe subset of asthma exacerbations, and the critical asthma syndrome is an umbrella term for life-threatening asthma, status asthmaticus, and near-fatal asthma. According to the 2007 National Asthma Education and Prevention Program guidelines, a life-threatening asthma exacerbation is marked by an inability to speak, a reduced peak expiratory flow rate of

Urgent visits to the clinic and emergency department for acute severe asthma exacerbations are all too frequent. Existing national guidelines do not present consistent or specific recommendations for the evaluation and treatment of individual asthma patients in respiratory distress. In this vein, we propose the term "critical asthma syndrome" (CAS) to describe any child or adult who is at high risk for fatal asthma. Acute severe asthma, refractory asthma, status asthmaticus, and near-fatal asthma all describe CAS where physical exhaustion from the overwhelming work of breathing leads to respiratory arrest and death from hypoxia or related complications. The authors of this supplement seek to emphasize the importance of early recognition, prompt and coordinated evaluation, and treatment of CAS in the emergency department, hospital, and intensive care units by experienced healthcare provider teams. CAS is not severe persistent asthma where control of symptoms and prevention of exacerbations are targets of chronic disease management in the outpatient setting. The authors address the distinctions between the two entities throughout the supplement, and elaborate on the considerations important in the care of a critically ill patient, including the common errors to avoid. In addition, gaps in knowledge and clinical experience in regards to critical asthma are highlighted. Knowledge gaps include a lack of understanding of how to recognize CAS, how to coordinate and integrate hospital and outpatient resources, when to further phenotype patients with critical asthma in order to facilitate effective treatment, and how to prevent future acute exacerbations. Lastly, CAS is complicated by the fact that asthma care in diverse healthcare settings is haphazard. We recommend that primary care physicians refer patients promptly to an asthma specialist for consultation to reduce the frequency of acute exacerbations and prevent the development of CAS.

The critical asthma syndrome (CAS) encompasses the most severe, persistent, refractory asthma patients for the clinician to manage. Personalized pharmacotherapy is necessary to prevent the next acute severe asthma exacerbation, not just the control of symptoms. The 2007 National Asthma Education and Prevention Program Expert Panel 3 provides guidelines for the treatment of uncontrolled asthma. The patient’s response to recommended pharmacotherapy is highly variable which risks poor asthma control leading to frequent exacerbations that can deteriorate into CAS. Controlling asthma symptoms and preventing acute exacerbations may be two separate clinical activities with their own unique demands. Clinicians must be prepared to use the entire spectrum of asthma medications available but must concurrently be aware of potential drug toxicities some of which can paradoxically worsen asthma control. Medications normally prescribed for COPD can potentially be useful in the CAS patient, particularly those with asthma-COPD overlap syndrome. Immunomodulation with drugs like omalizumab in IgE-mediated asthma syndromes is one important approach. New and emerging drugs address unique aspects of airway inflammation and biology but at a significant financial cost. The pharmacology and toxicities of the agents that may be used in the treatment of CAS to control asthma symptoms and prevent severe exacerbations are reviewed.

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a commonly encountered yet loosely defined clinical entity. ACOS accounts for approximately 15-25% of the obstructive airway diseases and patients experience worse outcomes compared with asthma or COPD alone. Patients with ACOS have the combined risk factors of smoking and atopy, are generally younger than patients with COPD and experience acute exacerbations with higher frequency and greater severity than lone COPD. Pharmacotherapeutic considerations require an integrated approach, first to identify the relevant clinical phenotype(s), then to determine the best available therapy. The authors discuss the array of existing and emerging classes of drugs that could benefit those with ACOS and share their therapeutic approach. A consensus international definition of ACOS is needed to design prospective, randomized clinical trials to evaluate specific drug interventions on important outcomes such as lung function, acute exacerbations, quality of life and mortality.

Pulmonary vasculitides represent a diverse group of diseases typified by nonspecific signs and symptoms with evidence of systemic extra-pulmonary organ involvement, including skin, kidney, and neurological systems. No single confirmatory diagnostic laboratory test exists; therefore the clinician must combine a thorough history and physical examination with other objective findings to make the correct diagnosis.

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. Clinicians and researchers have only recently recognized the disease heterogeneity and systemic consequences from tobacco smoking in aging COPD patients. Diagnosis and management of COPD and its acute exacerbations that begin to occur regularly after FEV1 has declined to less than 40–60% of predicted is a conundrum encountered frequently in clinical practice. Perhaps the most important challenge is the need to diagnose COPD in earlier stages, beginning in the fifth decade of life, at least a decade before the ­familiar albeit terminal phenotypes of chronic bronchitis (“blue bloater”) and emphysema (“pink puffer”) emerge. Persisting poor exercise tolerance despite the use of bronchodilators and inhaled corticosteroids should alert the clinician to the presence of co-morbidities associated with COPD, especially those that resemble acute exacerbation. COPD can often present as conundrums, singularly or severally in a patient. Thus enhancing the knowledge, skills and professional performance of an integrated COPD health care team to provide comprehensive COPD management may improve patient outcomes via early treatment and/or prevention of ­serious complications secondary to COPD.

Chronic obstructive pulmonary disease (COPD) is a debilitating pulmonary disorder with systemic effects, and it is the fourth leading cause of death in the United States. COPD patients not only develop respiratory limitations, but can also demonstrate systemic wasting, features of depression, and can succumb to social isolation. Smoking cessation is crucial, and pharmacotherapy with bronchodilators is helpful in symptom management. Inhaled corticosteroids may be beneficial in some patients. In addition, pulmonary rehabilitation and palliative care are important components under the right clinical circumstance. This review highlights current guidelines and management strategies for COPD and emphasizes novel pharmacotherapy and minimally invasive (nonsurgical) lung-volume reduction interventions that may prove to be of significant benefit in the future.

Many patients with breathlessness and chronic obstructive lung disease are diagnosed with either asthma, COPD, or—frequently—mixed disease. More commonly, patients with uncharacterized breathlessness are treated with therapies that target asthma and COPD rather than one of these diseases. This common practice represents the difficulty in distinguishing these disorders clinically, particularly in patients with a history that does not easily differentiate asthma from COPD. A common clinical scenario is an older former smoker with partially reversible or fixed airflow obstruction and evidence of atopy, demonstrating “overlap” features of asthma and COPD. We stress that asthma-COPD overlap syndrome becomes more prevalent with advancing age as patients respond less favorably to guideline-recommended drug therapy. We review the similarities and differences in clinical characteristics between these disorders, and their physiologic and inflammatory profiles within the context of the aging patient. We underscore the difficulties in differentiating asthma from COPD in current or former smokers, share our institutional experience with overlap syndrome, and highlight the need for new research to better characterize and investigate this important clinical phenotype.

Asthma in the adult patient is a complex clinical syndrome. Multiple patient phenotypes and subphenotypes exist that contribute to disease heterogeneity. Whether adult asthma begins in utero, develops in childhood, or manifests for the first time in adulthood is not completely understood, nor are the mechanisms fully delineated. In this chapter, we update definitions that apply to this group, emphasize epidemiologic factors and pathogenic mechanisms, diagnosis, therapeutic options, and controversies regarding drug safety. Finally, we provide a brief discussion of biomarker technologies and novel therapies with the potential to impact adult-onset asthma outcomes.

Nitrogen dioxide (NO2.) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO2. caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of alpha-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation, alpha-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of alpha-tocopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and alpha-tocopherol may be important agents protecting against NO2. in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO2..

Progress in improving patient outcomes and advancing therapeutics in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) is hampered by phenotypic heterogeneity and variable responsiveness to clinical interventions that are not fully explained by currently held disease paradigms for COPD and IPF. Although these chronic lung diseases differ in their geoepidemiology and immunopathogenesis, emerging evidence suggest that organ-specific autoimmunity may underlie subphenotypes of COPD and IPF. In particular, the links to tobacco smoking, diet, gender, and environment are explored in this review. We also highlight potential mechanisms that could guide future investigations in both laboratory and clinical settings. A paradigm shift is needed in how we think about COPD and IPF, based on geoepidemiology and a broader understanding of disease pathogenesis that may ultimately lead to new therapies and improved patient outcomes.

Vocal Fold Dysfunction is a syndrome characterized by abnormal adduction of the focal folds during inspiration and is the cause of a wide spectrum of clinical manifestations ranging from mild inspiratory stridor to an inability to move any air. Patients present with varying degrees of intermittent respiratory difficulty, the most severe caused by intense laryngospasm. Distinguishing Vocal Fold Dysfunction from Refractory Asthma is important to avoid unnecessary pharmacotherapy and intubation. The diagnosis of Vocal Fold Dysfunction can only be made with certainty by flexible fiberoptic laryngoscopy while the patient is symptomatic. Pulmonary function studies and a lack of response to bronchodilators may provide clues to the diagnosis. Most patients with the condition can be managed by speech therapy and the use of breathing strategies that eliminate the abnormal vocal fold movement. Chronic laryngeal irritation may be a trigger for Vocal Fold Dysfunction and conditions such as laryngopharyngeal reflux disease should be aggressively managed in this patient population.

Chronic obstructive pulmonary disease (COPD) exacts a heavy toll on society, yet its prevention, diagnosis and treatment receives inadequate attention from both the medical community and from society at large. Guidelines released in 2001 from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) are aimed at redressing this inequity. In this review, we integrate information from the GOLD guidelines with recent updates on the prevention, treatment and management as related specifically to the most severe form of this disease. In order to help distinguish COPD from other disorders that may mimic or confound its treatment, we place particular emphasis on the definition, underlying pathophysiology and diagnosis of COPD. In addition, we discuss future directions in pharmacotherapy.

Acute severe asthma calls for aggressive and early therapy of a multifaceted and all-inclusive approach (Fig. 2). Therapy merely begins in the ED and manifold distinct issues need to find consideration during ongoing hospital care. Currently, beta-agonists, anti-cholinergic agents, and corticosteroids remain the mainstay of therapy. Methylxanthines and magnesium may find consideration in carefully selected patients. Multiple new therapeutic avenues, such as the anti-leukotriene drugs, seem promising and future studies will hopefully extend our armamentarium against life threatening complication of a common disease. Asthma education begun in the hospital may provide the platform for preventing severe acute exacerbations and hospitalization.

The primary categories of pain are nociceptive and neuropathic. The assessment should focus on understanding the category, cause, and additional emotional and environmental factors that relate to the patients’s pain. Nociceptive pain is usually very responsive to opioids and NSAIDS. Neuropathic pain may respond better to antidepressants, anticonvulsants, antiarrhythmics, and sympatholytics. Treatment of related emotional and environmental factors will improve outcomes. Examining coexisting medical and psychosocial conditions can help to prevent poor outcomes and complications. Careful taking of the history and performance of the physical examination should provide the critical diagnostic information. Pain medications have considerable potential for side effects and drug interactions. It is important to obtain careful medication histories. The evaluation should include a screening assessment of the patient’s psychological state, which can uncover signs that more formal pscyhological assessment is needed. Misdiagnosis of brochial asthma is common in adults. Remember bronchial asthma is a heterogenous group of chronic lung disorders characterized by common nonspecific signs and symptoms. Different types of asthma will require diffeent treatments. Clinical overlap with other co-existing conditions, e.g. COPD chronic sinusitis, gastroesophageal reflux disease in common. Asthma patient education is fundamental to an effective treatment and management program. Control of airway inflammation, avoidance of environmental triggers, and individualized pharmacological interventions are essential. Failure to properly manage the inflammatory component of asthma risks increases patient morbidity amd mortality. Prevent acute asthmas exacerbations by controlling triggers and encouraging compliance with controller medications. Women with persistent asthma are at significantly higher risks for developing acute severe exacerbations compared to men. Keep exacerbations as far apart as possible. The key to reducing ashtma morbidity and mortality is prevention. Patient asthma action plans utilizing peak flow monitoring and a combination of controller(s) and reliever drugs to prevent and ameliorate attracks are proven treatment strategies. Personalized treatment plans improve compliance. Consider referring patients who are hospitalized for asthma exacerbations and those with difficult to control asthma to a consultant and/or a pulmonary rehabilitation program. The treatment of elderly adults and pregnant women with asthma differs significantly from that of younger adults. Potential for drug interactions and is greater in the elderly with co-existing medical conditions. The majority of asthma deaths are preventable. Undertreatment of asthma poses a greater risk for death than overtreatment.

Antioxidants present within lung epithelial lining fluids (ELFs) constitute an initial line of defense against inhaled environmental oxidants such as ozone, nitrogen oxides, and tobacco smoke, but the antioxidant composition of human ELFs is still incompletely characterized. We analyzed ELF concentrations of the low-molecular-mass antioxidants ascorbate, urate, glutathione (GSH), and alpha-tocopherol by obtaining bronchoalveolar lavage (BAL) and nasal lavage fluids from healthy nonsmoking volunteers and compared two different BAL procedures. ELF dilution by the lavage procedures was estimated by measurement of urea in recovered BAL fluids in comparison with those in blood plasma from the same subjects. The results indicated that a recently developed single-cycle BAL procedure minimizes influx of non-ELF urea into the instilled fluid and thus allows for a more accurate determination of ELF antioxidant concentrations. Using this procedure, we determined that bronchoalveolar ELF contains 40 +/- 18 (SD) microM ascorbate, 207 +/- 167 microM urate, 109 +/- 64 microM GSH, and 0.7 +/- 0.3 microM alpha-tocopherol (n = 12 subjects). Similar analysis of nasal lavage fluid yielded nasal ELF levels of 28 +/- 19 microM ascorbate and 225 +/- 105 microM urate (n = 12 subjects), whereas GSH was undetectable (0.5 microM). Our results demonstrate that ascorbate and urate are major low-molecular-mass ELF antioxidants in both the upper and lower respiratory tract, whereas GSH is present at significant concentrations only in bronchoalveolar ELF.

Publisher Summary Adult respiratory distress syndrome (ARDS) describes a life-threatening acute lung injury involving a heterogenous group of critically ill patients with hypoxemic respiratory failure who require mechanical ventilation, PEEP, and a high partial pressure of inspired O2. Clinical studies have established sepsis, aspiration of gastric contents, and major remote organ trauma as the most common disorders associated with high risk for ARDS. Pathologically, ARDS is a common response of the lung to variety of different and frequently unrelated insults. One important consequence is the alteration in permeability of alveolar epithelial and microvascular endothelial membrane barriers, and the upregulation of phagocytic, endothelial, and epithelial cell adhesion molecules. The physiologic result is hypoxemic acute respiratory failure because of lung ventilation-perfusion mismatching and extensive intrapulmonary shunts. The acute phase of ARDS (0-5 days) is characterized by a sudden wave of inflammatory-immune system activation. Activated alveolar macrophages (AMs) and neutrophils (PMNs) recruited to the lung from the peripheral circulation by inflammatory chemokines, cytokines, and other humoral mediators appear to combine to cause varying degrees of injury to both lung capillaries and alveolar epithelium. A network of cytokines and growth factors mediates a subacute or early reparative stage of lung injury characterized by proliferation of alveolar type II cells, which repopulate the denuded alveolar epithelium. Patients who survive from ARDS at this stage can either recover near normal lung function or enter a chronic phase (1-2 weeks) characterized by fibrosing alveolitis, pulmonary vascular microthrombosis, and loss of normal lung architecture. This chapter provides a perspective of the mechanisms underlying ARDS based on recent basic science and clinical investigations. The chapter details pathobiologic considerations—injury and inflammation, humoral aspects, cellular aspects, reactive oxygen and nitrogen species, and sepsis syndrome—therapeutic strategies—recent advances in mechanical ventilation, surfactant, nitric oxide (NO), anti-inflammatory agents, and immunologic and antioxidant therapies.