Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL). METHODS: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only. In the first group, an autologous endonasal mucosal graft from the nostril floor was placed bilaterally onto the ethmoidal roof. Endoscopic, radiological and QoL outcomes were compared before and one year after surgery between the two groups using Modified Lund Kennedy (LKM), Meltzer and Lund Mackay (LM) scores, and the Sino-Nasal Outcome Test 22 (SNOT-22). RESULTS: 64 patients with homogeneous baseline characteristics were included: 17 patients underwent a reboot surgery plus a bilateral mucoplasty and 47 a reboot surgery only. LKM, Meltzer and SNOT-22 scores showed significant differences before and after surgery in both groups, with higher improvement in the mucoplasty group. A greater mean improvement of 20.5 ± 6.4 points in SNOT-22 change was associated with bilateral mucoplasty. CONCLUSION: Bilateral mucoplasty plus reboot surgery constitutes a useful surgical resource in Type-2 CRSwNP patients, showing improved endoscopic, radiological and QoL outcomes one year after surgery. Further studies are needed to determine their long-term benefits.