Rohit Divekar

Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation.

Purpose of reviewAllergic diseases are thought to be driven by aberrant immune responses. Epithelium responds to various environmental factors by releasing key cytokines, such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25. Although there are important differences among these cytokines, there are also similarities which confound a clear understanding of the exact roles of these cytokines. The purpose of this review is to analyze the advances in biology and functions of these cytokines over recent years, elucidate their differences and similarities, and provide new conceptual understanding as to their roles in allergic diseases. Recent findingsThere are distinct differences in the timing, onset, and kinetics of the responses and perhaps in the potency of action of TSLP, IL-33, and IL-25. Newer roles of these cytokines have been described, including airway remodeling and fibrosis-related functions (TSLP, IL-33, and IL-25), fetal–maternal interface (IL-33 and TSLP), T-cell biology (TSLP), group 2 innate lymphoid cell biology (TSLP, IL-33, and IL-25), and mast cell–neutrophil axis (IL-33). Novel roles of these cytokines in the pathogenesis of atopic dermatitis and asthma have also been described. SummaryTSLP, IL-25, and IL-33 are increasingly recognized to play important roles in the pathophysiology of allergic diseases. More clear recognition of the differences and similarities of the immunological pathways mediated by these cytokines would help optimize the treatment for allergic diseases.

Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GM-CSF signatures during symptomatic exacerbations

The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease.

Clinical and 22-item Sino-Nasal Outcome Test symptom patterns in primary headache disorder patients presenting to otolaryngologists with "sinus" headaches, pain or pressure.

The objective of this work was to study patient and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) characteristics in primary headache disorders (PHDs).

Strategies for Molecular Classification of Asthma Using Bipartite Network Analysis of Cytokine Expression

Asthma is a chronic inflammatory disease of the airways that leads to various degrees of recurrent respiratory symptoms affecting patients globally. Specific subgroups of asthma patients have severe disease leading to increased healthcare costs and socioeconomic burden. Despite the overwhelming prevalence of the asthma, there are limitations in predicting response to therapy and identifying patients who are at increased risk of morbidity. This syndrome presents with common clinical signs and symptoms; however, awareness of subgroups of asthma patients with distinct characteristics has surfaced in recent years. Investigators attempt to describe the phenotypes of asthma to ultimately assist with diagnostic and therapeutic applications. Approaches to asthma phenotyping are multifold; however, it can be partitioned into 2 essential groups, clinical phenotyping and molecular phenotyping. Innovative techniques such as bipartite network analysis and visual analytics introduce a new dimension of data analysis to identify underlying mechanistic pathways.

Gender-specific differences in chronic rhinosinusitis patients electing endoscopic sinus surgery.

The objective of this study was to investigate gender‐specific differences in chronic rhinosinusitis (CRS) patients electing endoscopic sinus surgery (ESS).

Symptom-Based Clustering in Chronic Rhinosinusitis Relates to History of Aspirin Sensitivity and Postsurgical Outcomes

BACKGROUND Symptoms burden in chronic rhinosinusitis (CRS) may be assessed by interviews or by means of validated tools such as the 22-item SinoNasal Outcome Test (SNOT-22). However, when only the total SNOT-22 scores are used, the pattern of symptom distribution and heterogeneity in patient symptoms is lost. OBJECTIVES To use a standardized symptom assessment tool (SNOT-22) on preoperative symptoms to understand symptom heterogeneity in CRS and to aid in characterization of distinguishing clinical features between subgroups. METHODS This was a retrospective review of 97 surgical patients with CRS. Symptom-based clusters were derived on the basis of presurgical SNOT-22 scores using unsupervised analysis and network graphs. Comparison between clusters was performed for clinical and demographic parameters, postsurgical symptom scores, and presence or absence of a history of aspirin sensitivity. RESULTS Unsupervised analysis reveals coclustering of specific symptoms in the SNOT-22 tool. Using symptom-based clustering, patients with CRS were stratified into severe overall (mean total score, 90.8), severe sinonasal (score, 62), moderate sinonasal (score, 40), moderate nonsinonasal (score, 37) and mild sinonasal (score, 16) clusters. The last 2 clusters were associated with lack of history of aspirin sensitivity. The first cluster had a rapid relapse in symptoms postoperatively, and the last cluster demonstrated minimal symptomatic improvement after surgery. CONCLUSION Symptom-based clusters in CRS reveal a distinct grouping of symptom burden that may relate to aspirin sensitivity and treatment outcomes.

Unsupervised network mapping of commercially available immunoassay yields three distinct chronic rhinosinusitis endotypes

Endotyping chronic rhinosinusitis (CRS) through simplified cytokine assays may help direct individualized therapy such as corticosteroids, antibiotics, or biologics. We performed an unsupervised network analysis to endotype CRS and control subjects using a commercially available cytokine‐chemokine immunoassay.

Urinary Leukotriene E4 to Determine Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis

BACKGROUND Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. OBJECTIVE To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies. METHODS We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed. RESULTS The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively. CONCLUSIONS ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.

Gender-specific analysis of outcomes from endoscopic sinus surgery for chronic rhinosinusitis

Women electing endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) report higher symptom burden but have lower computed tomography (CT) scores. Gender‐specific analysis of outcomes from ESS therefore merits further study. The objective of this work was to study gender‐specific differences in outcomes from ESS for CRS by analyzing preoperative and postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores.

The role of visual analytics in asthma phenotyping and biomarker discovery.

The exponential growth of biomedical data related to diseases such as asthma far exceeds our cognitive abilities to comprehend it for tasks such as biomarker discovery, pathway identification, and molecular-based phenotyping. This chapter discusses the cognitive and task-based reasons for why methods from visual analytics can help in analyzing such large and complex asthma data, and demonstrates how one such approach called network visualization and analysis can be used to reveal important translational insights related to asthma. The demonstration of the method helps to identify the strengths and limitations of network analysis, in addition to areas for future research that can enhance the use of networks to analyze vast and complex biomedical datasets related to diseases such as asthma.