Gene Transcription Changes in Asthmatic Chronic Rhinosinusitis with Nasal Polyps and Comparison to Those in Atopic Dermatitis

Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases

Correlation between Nasal Symptoms and Nasal Nitric Oxide at Baseline and while Humming

Background: Chronic rhinosinusitis (CRS) is important in asthma and chronic cough assessment. An accurate diagnosis of CRS based solely on symptoms and nasal endoscopy can be difficult. Sinus CT-imaging is usually recommended in patients with negative rhinoscopy. Nasal nitric oxide (nNO) levels obtained passively and while humming are decreased in sinusitis due to ostiomeatal complex blockage of paranasal sinus gas exchange by inflamed tissue. A nNO measurement is a potential point-of-care test (POCT) for CRS. The SinoNasal Outcome Test (SNOT-20) is a clinical tool to assess symptoms in CRS.Objective: To evaluate if nNO levels provided objective information about CRS that would correlate with individual elements in the SNOT-20 and 6 additional CRS related symptoms. To examine these 26 symptom parameters for related clusters, and test correlation of the clusters with nNO measurements.Methods: In 180 patients, basal and humming nNO level measurements, and 26 symptoms (SNOT-20 plus 6 added items) were collected. Hierarchical cluster analysis was applied to sort the data into clusters.Results: The 26 questions grouped into 5 different clusters. 2 clusters contained questions that were most disease specific for sinonasal diseases in patients referred for subspecialty asthma and chronic cough evaluation. We demonstrated that nNO levels during humming, and the ratio between humming and basal nNO, correlated best with clusters 2 and 4.Conclusion: Baseline and humming nNO measurements provide objective information about CRS. nNO measurements offers the potential of a POCT for objective assessment of CRS in patients presenting to a pulmonary clinic