Dupilumab Improves Nasal Polyp Burden and Asthma Control in Patients With CRSwNP and AERD

In the difficult-to-treat subgroup of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid aspirin-exacerbated respiratory disease, dupilumab significantly improved CRSwNP disease outcomes, along with asthma control and lung function. This is preliminary evidence of the effect of dupilumab in patients with CRSwNP and comorbid aspirin- exacerbated respiratory disease

Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review

Background: The prevalence rates of depressive and anxiety disorders are high in residential aged care settings. Older adults in such settings might be prone to these disorders because of losses associated with transitioning to residential care, uncertainty about the future, as well as a decline in personal autonomy, health, and cognition. Cognitive behavioral therapy (CBT) is efficacious in treating late-life depression and anxiety. However, there remains a dearth of studies examining CBT in residential settings compared with community settings. Typically, older adults living in residential settings have higher care needs than those living in the community. To date, no systematic reviews have been conducted on the content and the delivery characteristics of CBT for older adults living in residential aged care settings. Objective: The objective of this paper is to describe the systematic review protocol on the characteristics of CBT for depression and/or anxiety for older adults living in residential aged care settings. Methods: This protocol was developed in compliance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Studies that fulfill the inclusion criteria will be identified by systematically searching relevant electronic databases, reference lists, and citation indexes. In addition, the PRISMA flowchart will be used to record the selection process. A pilot-tested data collection form will be used to extract and record data from the included studies. Two reviewers will be involved in screening the titles and abstracts of retrieved records, screening the full text of potentially relevant reports, and extracting data. Then, the delivery and content characteristics of different CBT programs of the included studies, where available, will be summarized in a table. Furthermore, the Downs and Black checklist will be used to assess the methodological quality of the included studies. Results: Systematic searches will commence in May 2018, and data extraction is expected to commence in July 2018. Data analyses and writing will happen in October 2018. Conclusions: In this section, the limitations of the systematic review will be outlined. Clinical implications for treating late-life depression and/or anxiety, and implications for residential care facilities will be discussed

Effect of Dupilumab on Sleep Apnea Severity in Patients With Chronic Rhinosinusitis

Patients with chronic rhinosinusitis (CRS) report improved sleep quality after dupilumab, an anti IL4/13 therapy. Concurrent CRS and obstructive sleep apnea (OSA) cases are not rare, and CRS seemingly raises nasal resistance. Thus, we hypothesized that improved sleep quality by dupilumab therapy in CRS patients might be due to lowered nasal resistance and subsequent improvement of unrecognized comorbid OSA. Patients with concurrent CRS and OSA were recruited. Nasal resistance was measured invasively with transnasal pressure and flow data collected during normal respiration in the supine position. Results from the first five participants did not support our hypothesis. Subjective and objective measures for CRS and nasal resistance values were improved with dupilumab therapy in CRS patients with nasal polyps. However, apnea severity and sleep-related subjective parameters did not change. In the patients with CRS without nasal polyps, no significant changes in either CRS or OSA-related measures were observed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pathogenesis of NSAID-induced reactions in aspirin-exacerbated respiratory disease

It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter's disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually involves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Pretreatment with medications that inhibit the leukotriene pathway decreases the severity of clinical reactions, which points to the involvement of cysteinyl leukotrienes (cysLTs) in the pathogenesis of these aspirin-induced reactions. Furthermore, studies of aspirin challenges in carefully-phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D2, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin-induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD2, are likely to be major participants in the acute reactions, and are an attractive target for future pharmacotherapies in AERD. Although several recent studies support the role of platelets as inflammatory effector cells and as a source of cysLT overproduction in AERD, it is not yet clear whether platelet activation plays a direct role in the development of the aspirin-induced reactions. To further our understanding of the pathogenesis of aspirin-induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required. Keywords: Aspirin-exacerbated respiratory disease (AERD), Nasal polyps, Samter's triad, Pathogenesis, Cysteinyl leukotrienes, Prostaglandins, Mast cel

Update on the Management of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD

Pathomechanisms of AERD - recent advances

Peer reviewe

Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level

Abstract To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab. We defined clinical response as a reduction in the baseline annual exacerbation rate by half or more over the one-year period following initiation of the biologic. Baseline levels of plasma IL-13 were differentially elevated in responders versus non-responders to mepolizumab and plasma CXCL10 levels were differentially elevated in responders to omalizumab. The ratio of IL-13/TNF-α had the best sensitivity and specificity in predicting response to mepolizumab and CXCL10/CCL17 to omalizumab, and these performed better as predictive biomarkers of response than BEC and IgE. Cytokines and chemokines associated with airway eosinophilia, allergic inflammation, or Th2 inflammation, such as IL-13 and CXCL10, may be better predictors of clinical response to mepolizumab and omalizumab, than IL-5 or IgE, the targets of mepolizumab and omalizumab

The Role of Biologics in Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease of the upper respiratory tract. This article provides expert opinion and points of view from both allergists and rhinologists who specialize in CRSwNP. Despite the potential value of biomarker-based endotyping to provide guidance regarding optimal care and treatment choices for patients with CRSwNP, current practice is largely not biomarker-based. In general, there is agreement that for patients with symptomatic CRSwNP who have failed a trial of a course of at least 3 months of intranasal steroids and a short course of oral corticosteroids, a surgical intervention will often be the next treatment of choice. Biologics may be considered before an initial surgery in patients with comorbid severe asthma and in those for whom surgery is less available, refused by the patient, or likely to be associated with a higher-than-average complication rate. Biologic use immediately following surgery may be considered in patients who have a history of nasal polyp recurrence within 12 months of a prior surgery. For many patients with recalcitrant disease, a combination of sinus surgery and use of a biologic that is targeted to their precise endotype may be the optimal treatment strategy, though which surgical approach and which biologics are best for each patient are debates that remain ongoing

Automated identification of an aspirin-exacerbated respiratory disease cohort

BACKGROUND Aspirin-exacerbated respiratory disease (AERD) is characterized by 3 clinical features: asthma, nasal polyposis, and respiratory reactions to cyclooxygenase-1 inhibitors (nonsteroidal anti-inflammatory drugs). Electronic health records (EHRs) contain information on each feature of this triad. OBJECTIVE We sought to determine whether an informatics algorithm applied to the EHR could electronically identify patients with AERD. METHODS We developed an informatics algorithm to search the EHRs of patients aged 18 years and older from the Partners Healthcare system over a 10-year period (2004-2014). Charts with search terms for asthma, nasal polyps, and record of respiratory (cohort A) or unspecified (cohort B) reactions to nonsteroidal anti-inflammatory drugs were identified as "possible AERD." Two clinical experts reviewed all charts to confirm a diagnosis of "clinical AERD" and classify cases as "diagnosed AERD" or "undiagnosed AERD" on the basis of physician-documented AERD-specific terms in patient notes. RESULTS Our algorithm identified 731 "possible AERD" cases, of which 638 were not in our AERD patient registry. Chart review of cohorts A (n = 511) and B (n = 127) demonstrated a positive predictive value of 78.4% for "clinical AERD," which rose to 88.7% when unspecified reactions were excluded. Of those with clinical AERD, 12.4% had no mention of AERD by any treating caregiver and were classified as "undiagnosed AERD." "Undiagnosed AERD" cases were less likely than "diagnosed AERD" cases to have been seen by an allergist/immunologist (38.7% vs 93.2%; P < .0001). CONCLUSIONS An informatics algorithm can successfully identify both known and previously undiagnosed cases of AERD with a high positive predictive value. Involvement of an allergist/immunologist significantly increases the likelihood of an AERD diagnosis