Recurrent Exacerbations Research Articles

Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies.

Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called “gene editing” to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics. Standardized care at specialized centers using a multidisciplinary approach that imposes surveillance of lung function and of airway biofilm composition likely improves patients’ outcome. Pediatricians, neonatologists, pulmonologists, and ENT surgeons should maintain high awareness of PCD and refer patients to the specialized center before sustained irreversible lung damage develops. The recent creation of a network of PCD clinical centers, focusing on improving diagnosis and treatment, will hopefully help to improve care and knowledge of PCD patients.

Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013.

Bronchiectasis is an incurable pulmonary disorder that is characterized pathologically by permanent bronchial dilatation and severe bronchial inflammation and clinically by chronic productive cough and recurrent infectious exacerbations; bronchiectasis often occurs in the presence of chronic obstructive pulmonary disease. It is widely believed that increasing use of high-resolution computed tomography has led to a marked rise in the number of persons with diagnosed bronchiectasis in current US clinical practice; up-to-date evidence, however, is lacking. Using a retrospective cohort design and health-care claims data (2009–2013), we estimated the prevalence of bronchiectasis (noncystic fibrosis)—based on narrow case-finding criteria—to be 139 cases per 100,000 persons, to be higher among women versus men (180 vs. 95 per 100 K), and to increase substantially with age (from 7 per 100 K to 812 per 100 K aged 18–34 years and ≥75 years, respectively); annual incidence was estimated to be 29 cases per 100,000 persons. Disease prevalence based on broad case-finding criteria was estimated to be 213 cases per 100,000 persons. The findings of this study suggest that between 340,000 and 522,000 adults were receiving treatment for bronchiectasis and that 70,000 adults were newly diagnosed with bronchiectasis, in 2013 US clinical practice. The findings of this study also suggest that bronchiectasis is much more common than previously reported (annual growth rate since 2001, 8%), presumably due—at least in part—to recent advances in, and increased use of, radiologic techniques. Additional research is needed to validate the findings of this study, to identify the reasons for increased prevalence, and to promote education about bronchiectasis nationally.

New opportunities for prevention of exacerbations of chronic obstructive pulmonary disease. Russian Respiratory Society Expert Opinion

Combination therapy with long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) can reduce symptoms of chronic obstructive pulmonary disease (COPD) and the risk of future exacerbations. To date, the only fixed combination of long-acting bronchodilators, indacaterol/glycopyrronium, has demonstrated a significant reduction in dyspnea and in the risk of moderate and severe exacerbations of COPD in clinical trials when compared with the combination of salmeterol/fluticasone. Addition of inhaled steroids (ICS) to long-acting bronchodilators is recommended for patients with recurrent COPD exacerbations, especially in those with asthma-COPD overlap syndrome or history of elevated blood or sputum eosinophil levels. It is recommended to consider phenotype-specific therapy including roflumilast, N-acetylcysteine, and macrolides, in patients who continue to exacerbate despite being treated with LABA/LAMA or LABA/LAMA/ICS combinations. Withdrawal of inhaled corticosteroids is possible in patients with the low risk of exacerbation and in those with severe adverse events during ICS treatment. ICS should be withdrawn in a single step in patients with no repeated exacerbations during 12 months and with moderate bronchial obstruction (FEV1 ≥ 50% predicted). Stepwise withdrawal of ICS during 3 month with continuous dual bronchodilator therapy is recommended in COPD patients with severe bronchial obstruction (FEV1 ˂ 50% predicted) without frequent exacerbations in the previous year.

Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study

BackgroundInfective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD.MethodsWe undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages. The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression. To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates.ResultsThe percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years. In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations. COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (<20%).ConclusionsHigh hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD.

Abstract 088: Characteristics of Congestive Heart Failure Patients Included in The Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program

Background: The Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program (HRRP) has created financial penalties for hospitals with higher risk-standardized readmission rates after hospitalization for specific conditions, including congestive heart failure (CHF). Identification and risk-standardization is performed with administrative data. Both to evaluate the utility of this metric for improving quality and to inform efforts by providers to reduce readmissions, more granular clinical information about patients included in the penalty is needed. Methods: All patients who contributed to the CHF component of the HRRP penalty at our hospital between June, 2012 and December, 2013 were identified and medical records were reviewed by a physician (A.J.C.). Information extracted included index inpatient service, cause of readmission, medications, scheduled follow-up, whether echocardiogram was performed, NT pro-BNP as measured at admission and discharge, weight documented during index hospitalization, last known ejection fraction, and discharge disposition. Results: During this time period, 212 readmitted CHF patients contributed to the HRRP penalty. Of those, 31 (14.6%) were excluded due to readmission to an outside hospital. Of the remaining 181, 6 (2.8%) were excluded as the cause of index admission was not confirmed to be CHF. These patients were excluded from all analyses. Of the remaining 175 patients, 79 (45.1%) were readmitted for recurrent CHF exacerbation while 96 (54.8%) were readmitted for reasons other than CHF. Seventy (40%) patients were discharged home with visiting nurse services, 44 (25.1%) discharged home without services, and 61 (34.9%) discharged to a skilled nursing facility. Of the 114 patients discharged home, 44 (38.6%) had follow-up scheduled at the time of discharge. The median length of time between the index admission and readmission was 13 days. Among the 79 patients readmitted for CHF-related causes, 39 (49.4%) initially had been hospitalized on the cardiology service while 40 (50.6%) were hospitalized on a general medical service. Of those 79 patients, 32 (40.5%) had left ventricular systolic dysfunction (LVSD). At time of index discharge, 28 (87.5%) of patients with LVSD had been prescribed a beta blocker and 12 (37.5%) had been prescribed an ACE inhibitor or ARB. Conclusions: About half of patients who contributed to the CHF component of the HRRP penalty at our hospital were readmitted for recurrent CHF, the other half for different diagnoses. Of those who were readmitted with recurrent CHF, more than half did not have systolic dysfunction. Many of the patients with recurrent CHF due to systolic dysfunction were not initially discharged on ACE or ARB therapy, largely due to hypotension or renal dysfunction. These findings underscore the challenges of reducing preventable hospital readmission in this HRRP penalty population.

Clinical Mimics: An Emergency Medicine–Focused Review of Asthma Mimics

BackgroundAsthma is a common diagnosis or preexisting condition, and many patients with acute asthma exacerbation may present to the emergency department with wheezing and respiratory distress. However, many conditions may mimic this presentation. ObjectivesThis review provides an overview of common asthma mimics and an approach to evaluation and management. DiscussionAsthma is characterized by an obstructive pulmonary disease with recurrent exacerbations. The disease may present with a variety of symptoms, including wheezing, chest tightness, shortness of breath, and even respiratory failure. Mimics include anaphylaxis, angioedema, central airway obstruction, heart failure, allergic reaction, foreign body aspiration, pulmonary embolism, and vocal cord dysfunction. The approach to evaluation and management of these patients includes assessment for life-threatening conditions while treatment and resuscitation is underway. Providers should assess for red flags, including no history of asthma, lack of severe asthma, and no improvement with standard treatments. Focused assessment with history, physical examination, chest imaging, electrocardiogram, and laboratory studies may provide benefit. Through consideration of these mimics and treatment, providers can provide rapid management. ConclusionsWhile asthma is a common disease, many asthma mimics exist. Through consideration of other diseases with wheezing and assessing for red flags, such as patients presenting without a history of asthma or patients with a history of only mild asthma presenting with severe symptoms, emergency providers may decrease the chance of early diagnostic closure and anchoring while improving the care of these patients.

Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region

Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region

Club cell secretory protein serum concentration is a surrogate marker of small-airway involvement in asthmatic patients

Poor asthma control and recurrent exacerbations have been shown to be a phenotypic counterpart of asthma with predominantly small-airway involvement.1 Biomarkers are not always accurate in asthmatic patients, especially in serum, because compartmentalization can occur between the blood and airways. Blood eosinophil counts do not represent an overall view of airway inflammation, and exhaled nitric oxide measurements at different flow rates (fraction of exhaled nitric oxide [Feno] and alveolar nitric oxide [Calvno]) have been developed and validated to reflect more accurately proximal and distal airway inflammation.2 Club cell secretory protein (CCSP) serum concentration has been shown to be associated with chronic obstructive pulmonary disease, bronchiolitis obliterans syndrome, and sarcoidosis, which are all predominantly diseases involving the small airways. Ranges of CCSP concentrations in healthy subjects, reproducibility, and relationships between serum and airway levels are known and can be used as potential surrogate markers. Our aim was to assess small-airway disease in asthmatic patients and to find a related biomarker. We used a dynamic assessment of gas trapping using computed tomographic (CT) imaging of the chest during methacholine challenge as a marker of small-airway disease.

Real-life data on antibiotic prescription and sputum culture diagnostics in acute exacerbations of COPD in primary care.

BackgroundAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are generally treated with optimization of bronchodilation therapy and a course of oral corticosteroids, mostly without antibiotics. The Dutch guidelines recommend prudent use of antibiotics, with amoxicillin or doxycycline as first choice. Here we evaluate adherence to these guidelines with regard to antibiotic prescription in AECOPD in primary care and the use of sputum cultures.MethodsWe retrospectively analyzed a longitudinal cohort of patients in three primary care practices in the north-eastern region of the Netherlands from 2009 to 2013 (n=36,172 subjects) participating in the Registration Network Groningen. Antibiotics prescribed for AECOPD −10/+28 days from the start date of corticosteroid courses were evaluated. In addition, we assessed regional data on the susceptibility of respiratory pathogens from COPD patients.ResultsWe identified 1,297 patients with COPD. Of these, 616 experienced one or more exacerbations, resulting in a total of 1,558 exacerbations, for which 1,594 antibiotic courses were prescribed. The recommended antibiotics doxycycline and amoxicillin accounted for 56% of the prescribed antibiotics overall and for 35% in subsequent antibiotic courses. The alternative choices were not based on culture results because only in 67 AECOPD events (2.9%) sputum samples were taken. Regional data including 3,638 sputum samples showed that pathogens relevant in AECOPD were detected in 19% of cultures.ConclusionOur study shows that guidelines regarding the prescription of antibiotics are poorly followed, particularly in recurrent exacerbations. Sputum cultures were performed in a small minority of cases. Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment.

Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency.

PurposeRecurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD.MethodsThis is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion.ResultsA total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function.ConclusionsIVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. Six adolescents with CF (mean age, 16.2 y; mean FEV1, 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts). All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Long-term antibiotic treatment for non-cystic fibrosis bronchiectasis in adults: evidence, current practice and future use

ABSTRACTIntroduction: Bronchiectasis is defined pathologically by the permanent dilation of the bronchi and bronchioles and chronic airway inflammation. This is the outcome of a number of different aetiologies but up to half of bronchiectasis cases are labelled idiopathic. It is characterised by a chronic productive cough, haemoptysis, shortness of breath and recurrent infective exacerbations. Long-term antibiotics are used with the aim of reducing symptom severity and exacerbation frequency, improving quality of life and preventing disease progression.Areas covered: This perspective provides an overview of evidence and current practice for long-term oral, inhaled and pulsed intravenous antibiotic therapy in adults with non-cystic fibrosis bronchiectasis. Evidence was drawn from a recent systemic literature review.Expert commentary: An approach to long-term antibiotic treatment is provided. Side effects of treatment, methods of monitoring treatment success and actions to be considered if treatment fails are discussed. Emerging long-term antibiotic treatments and strategies are considered.

Nurse Staffing and 30-day Readmission of Chronic Obstructive Pulmonary Disease Patients: A 10-year Retrospective Study of Patient Hospitalization

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity in many countries, and it has high rate of hospital readmissions due to recurrent exacerbations of the disease. Many previous studies have suggested further examination of the factors that contribute to hospital readmissions of COPD patients. However, evidence on the effects of nurse staffing by registered nurses (RNs) on the readmission of COPD patients is lacking in Korea. The aim of our study was to evaluate the effects of nurse staffing on hospital readmissions of COPD patients. We used National Health Insurance claim data from 2002 to 2012. A total of 1,070 hospitals and 339,379 hospitalization cases were included in the analysis. We divided the number of RNs per 100 beds and the proportion of RNs on staff to one of three groups (Q1: low; Q2: moderate; Q3: high). A generalized estimating equation model was used to evaluate the associations between readmission and nurse staffing. A higher number of RNs was associated with lower readmission rates of 8.9% (Q2) and 7.9% (Q3) respectively. A similar effect was observed as the proportion of RNs among the total nursing staff gradually increased, resulting in lower readmission rates of 7.7% (Q2) and 8.3% (Q3). Our results suggest notable positive effects of nurse staffing by RNs on patient outcomes. In addition, the magnitude of impact differed between different sizes of hospitals. Thus, human resource planning to solve staffing shortages should carefully consider the qualitative aspects of the nursing staff composition.

Microstructural alterations of sputum in cystic fibrosis lung disease.

The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents.

Les traitements du futur de l’asthme sévère

Asthma is a very frequent disease with complex and heterogenous immunological and clinical features. Daily inhaled steroids are the cornerstone of the current therapeutics sometimes associated with long-acting β2-agonist. This controller treatment is effective and allows to control asthma symptoms for the vast majority of the patients. Severe asthma is characterized by a poor level of control of symptoms, with recurrent exacerbations or a chronic airflow limitation despite an optimal management. Severe asthma remains a difficult diagnosis but we have now studies proving the clinical efficacy or promising data about monoclonal antibodies targeting IgE, IL-5, IL-4 or IL-13. Most of these monoclonal antibodies target the Th2 type eosinophilic inflammation without any treatment against non-eosinophilic or Th1 inflammation. Last, it will be essential to assess accurately the cost effectiveness of these expensive treatments, to identify and to qualify the target population for each molecule and to assess its financial impact for the community.

Development of the respiratory tract microbiota in cystic fibrosis.

Progression of lung disease in cystic fibrosis (CF) is punctuated by Pseudomonas aeruginosa infection and recurrent pulmonary exacerbations, and is the major determinant of a patient's life expectancy. With the advent of novel deep-sequencing techniques, polymicrobial bacterial assemblages rather than single pathogens seem to be responsible for the deterioration of pulmonary function. This review summarizes recent insights into the development of the CF respiratory tract microbiome, with its determinants and its relations to clinical parameters. Research has moved from microbiota snapshots to intensive sampling over time, in an attempt to identify biomarkers of progression of CF lung disease. The developing respiratory tract microbiota in CF is perturbed by various endogenous and exogenous factors from the first months of life on. This work has revealed that both major pathogens such as P. aeruginosa and newly discovered players such as anaerobic species seem to contribute to CF lung disease. However, their interrelations remain to be unraveled. Long-term follow-up of microbiome development and alterations in relation to progression of lung disease and treatment is recommended. Moreover, integrating this information with other systems such as the metabolome, genome, mycome and virome is likely to contribute significantly to insights into host-microbiome interactions and thereby CF lung disease pathogenesis.

Interleukin-5 Antagonists Usher in a New Generation of Asthma Therapy.

Asthma is the most common chronic respiratory disease in the USA. A subset of patients with asthma have refractory symptoms, persistent eosinophilic inflammation, and recurrent exacerbations despite maximal medical therapy. The monoclonal antibodies targeting the IL-5 pathway are a new class of medications designed to target severe eosinophilic asthma. There are two medications clinically available: mepolizumab and reslizumab, both of which target IL-5. A third medication, benralizumab, is currently under development and targets the IL-5 receptor. Clinical data suggest these medications can reduce asthma exacerbations and improve lung function in patients with peripheral eosinophilia and poorly controlled asthma despite maximal medical therapy. The anti-IL-5 medications are among the first targeted molecular therapies for asthma and will usher in an exciting new era in the treatment of severe asthma.

A decade of domiciliary non-invasive ventilation in the west of Ireland.

While domiciliary non-invasive ventilation (NIV) was initially used in the treatment of respiratory failure resulting from chest wall deformity, the main indication is now chronic obstructive pulmonary disease (COPD) with recurrent exacerbations associated with type 2 respiratory failure. A longitudinal study of domiciliary NIV provides insights into the evolution of this treatment in the west of Ireland. The cohort of patients receiving new prescriptions for domiciliary NIV from Galway University Hospital from 2000 to 2012 was reviewed using study coordinator chart reviews and telephone follow-ups. In total, 161 patients were identified. Prescriptions for domiciliary NIV increased from 2 in 2000 to 35 in 2012. The most common indication between 2000 and 2006 was obesity hypoventilation syndrome (OHS), changing to COPD between 2007 and 2012. There were significantly higher mortality rates in COPD and neuromuscular disease at 1- and 3-year follow-up compared to OHS and chest wall disease. Patients with chest wall disease had most survival years (7.33±5.51) following initiation of domiciliary NIV when compared to patients with OHS (5.50±3.70) and COPD (3.03±1.89) and patients with neuromuscular disease (2.50±2.01). Domiciliary NIV use increased significantly in the West of Ireland from 2000 to 2012. There has been a shift in prescribing toward COPD. Survival rates for COPD on NIV are relatively short in contrast to patients with OHS and chest wall disease. Improved understanding of the benefits of NIV will allow physicians to better determine appropriate and cost-effective use in the future.

Strongyloides and Dieulafoy on Steroids

Introduction:Strongyloides infection typically manifests with pulmonary, gastrointestinal (GI) or dermatological symptoms and can remain asymptomatic for decades. Steroid-induced immunosuppression increases the parasite's pathogenicity and may lead to superimposed infectious complications. We describe a patient with a history of extensive steroid treatment for COPD exacerbations who had three simultaneous disorders in his GI tract: Strongyloides, Herpes Simplex virus and Dieulafoy's lesion. This unusual case highlights the importance of including Strongyloides in the differential diagnosis of patients from tropical regions presenting with both respiratory and GI symptoms, especially in patients with previous steroid exposure. Case Presentation: A 64-year-old Bengali male, who had moved from India to the United States 4 months prior, presented with dyspnea and wheezing. His medical history included COPD (active smoker), CAD, heart failure, and hypertension. He was treated with prednisone for a suspected COPD exacerbation and discharged home. Soon after, he experienced odynophagia to solids, which progressed to intolerance of both solids and liquids, continuing dyspnea and, within one week, melena. He returned to the hospital septic with enterocolitis noted on CT. Hemoglobin dropped from 12.1 to 6.3 in 3 days. He was HIV negative and had no eosinophilia. EGD revealed multiple ulcers in the middle third of the esophagus, gastritis, duodenitis, and one medium-sized, oozing Dieulafoy's lesion in the distal duodenal bulb. Biopsies showed esophageal HSV and Strongyloides in the duodenum. The patient was treated with ivermectin for strongyloidiasis and with intravenous acyclovir for HSV esophagitis with resolution of his GI symptoms. Discussion: The degree to which Strongyloides contributed to this patient's dyspnea is unclear, as the patient is an active smoker with recurrent COPD exacerbations; however, we hypothesize that he was chronically infected. Prednisone-induced immunosuppression likely resulted in HSV esophagitis and triggered disseminated strongyloidiasis, which may have precipitated bleeding from his pre-existing Dieulafoy's lesion. Rapid diagnosis and prompt antiparasitic treatment prevent mortality, which can be as high as 50 - 80%. Our case highlights potential asymptomatic chronic helminth infections in patients from endemic areas and alerts clinicians to the ramifications of prednisone use in this population.

Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study

PurposePatients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma. MethodsCOSMOS was a 52-week, open-label extension study in patients who received mepolizumab or placebo in MENSA or SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment allocation and continued to receive appropriate standard-of-care asthma therapy throughout. The primary objective was to assess the long-term safety of mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). Efficacy assessments included the annualized exacerbation rate and durability of response (defined as the exacerbation rate and OCS dose reduction when combined with MENSA and SIRIUS data, respectively). FindingsIn total, 558 (86%; previous mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, previous placebo: 36) patients experienced on-treatment AEs and SAEs, respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients experienced systemic and local site reactions, respectively. There were no reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to exert a durable response, with patients who previously received mepolizumab in MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS demonstrated improvements in these end points following treatment with mepolizumab in COSMOS. ImplicationsThese data demonstrate a favorable safety profile of mepolizumab and indicate a durable and stable effect over time, supporting long-term treatment in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT01842607.