Samant, Shefali

SummaryBackgroundThe 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.ObjectiveTo characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls.MethodsThis was a non‐interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post‐visit 2 weeks later. The sinonasal outcome test‐22 (SNOT‐22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis.ResultsBoth CRSwNP patients and control subjects showed a significant increase in SNOT‐22 scores during acute exacerbation. Increased nasal levels of IL‐6, IL‐5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM‐CSF levels were notable and were validated by a conventional analysis.ConclusionsCRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM‐CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.

AbstractBackgroundAsthma guidelines suggest reducing controller medications when asthma is stable.MethodsThe purpose of the study is to estimate the risk of asthma exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS) compared to those who maintain a stable ICS dose. We identified articles from a systematic review of English and non‐English articles using MEDLINE, EMBASE, Web of Science, and CENTRAL (inception to May 25, 2013). We included randomized controlled trials (RCTs) with a stable asthma run‐in period of 4 weeks or more, an intervention to reduce ICS, and a follow‐up period of at least 3 months.ResultsThe search strategy identified 2253 potential articles, of which 206 were reviewed at the full‐text level and 6 met criteria for inclusion. The relative risk of an asthma exacerbation in individuals who reduced ICS compared to those who maintained the same ICS dose was 1.25 (95% CI 0.96, 1.62; P = 0.10; I2 = 0%) in studies with a mean follow‐up of 22 weeks. Individuals who reduced ICS had a decreased% predicted FEV1 of 0.87% (95% CI −1.58%,3.33%; P = 0.49, I2 = 58%) and a decreased mean morning peak expiratory flow of 9.57 l/min (95% CI 1.25, 17.90; P = 0.02; I2 = 74%) compared to those individuals who maintained a stable ICS dose.ConclusionsAsthma exacerbations were statistically no more likely among individuals who reduced ICS compared to those who maintained their ICS dose, supporting current guidelines which recommend decreasing ICS by 50% after a period of asthma stability.

Background One way to gain insight into the pathophysiology of chronic rhinosinusitis (CRS) is to study the immunologic changes that occur with exacerbation. This study describes the immunologic changes during CRS exacerbation Methods We performed a prospective study to investigate the immunologic changes seen during exacerbation of CRS with nasal polyposis. We recruited adult subjects who met clinical criteria for CRS with sinus CT scan within the past 5 years with Lund-Mackay score of >5 and nasal polyps. Subjects underwent a baseline visit with collection of nasal secretion and nasal wash. With acute worsening of symptoms, subjects underwent 6 near-consecutive-day collections and one follow-up collection 2 weeks later. IL-6, IL-33, eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), myeloperoxidase (MPO), and uric acid were measured on the nasal samples from each visit. Results A total of 10 subjects were recruited and 9 had acute worsening of CRS during the study period. Eight of the nine subjects were women and ages ranged from 26 to 56 years. At baseline, most inflammatory parameters were low and eight of the nine subjects were on intranasal corticosteroids. Compared with baseline measurements, IL-6, MBP, MPO, EDN, and uric acid were significantly elevated during CRS exacerbation. Levels of IL-6 and MBP (r = 0.47) levels as well as IL-6 and MPO (r = 0.75) were both significantly correlated (p < 0.01). Conclusion Prospective study of CRS exacerbations is feasible and provides insights into the immunologic mechanisms of CRS.