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.

Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

Free nasal floor mucosal grafting after endoscopic total ethmoidectomy for severe nasal polyposis: a pilot study.

BACKGROUND: We report a novel surgical technique based on an endonasal free mucosal graft (mucoplasty) for improving clinical results and local healing in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Patients diagnosed with bilateral CRSwNP scheduled for endoscopic sinus surgery were included. They underwent complete removal of anterior and posterior ethmoid cells, in addition to bilateral type III frontal sinusotomy. An endoscopic mucoplasty was performed in the left nasal cavity, whereas the right nasal cavity served as control. Patients were evaluated before surgery and 6 months after operation, including Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS) for olfaction, endoscopic evaluation using the Modified und-Kennedy (MLK) scoring system and healing evaluation. RESULTS: Ten patients (mean age 53.6 years) were included. A significa t decrease of SNOT-22 score from 57.0 (21.1) to 20.3 (20.6) (P = 0.024) and a non-significa t decrease of VAS for olfaction score from 9.3 (0.5) to 4.6 (3.9) were found. Preoperative mean MLK score was 4.9 (0.7) in the right nostril and 4.8 (1.0) in the left one. After operation, there was a greater decrease of MLK score in the left nostril than in the right (1.9 [1.0] vs. 1.3 [0.8], P = 0.034). Better healing was proved in the nostril with the mucoplasty. CONCLUSION: Endonasal mucoplasty could be an effective, safe and feasible complementary surgical procedure in the treatment of CRSwNP. The reduced local edema associated with lower amount of secretions may confer a better control in the frontal recess, orbital wall and nasal roof.

Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes.

In the last years, regional differences have been reported between the brain and spinal cord oligodendrocytes, which should be considered when designing therapeutic strategies for myelin repair. Promising targets to achieve myelin restoration are the different components of the endocannabinoid system (ECS) that modulate oligodendrocyte biology, but almost all studies have been focused on brain-derived cells. Therefore, we compared the ECS between the spinal cord and cerebral cortex-derived oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (OLs). Cells from both regions express synthesizing and degrading enzymes for the endocannabinoid 2-arachidonoylglycerol, and degrading enzymes increase with maturation, more notably in the spinal cord (monoglyceride lipase-MGLL, alpha/beta hydrolase domain-containing 6-ABHD6, and alpha/beta hydrolase domain-containing 12-ABHD12). In addition, spinal cord OPCs express higher levels of the synthesizing enzymes diacylglycerol lipases alpha (DAGLA) and beta (DAGLB) than cortical ones, DAGLA reaching statistical significance. Cells from both the cortex and spinal cord express low levels of NAEs synthesizing enzymes, except for the glycerophosphodiester phosphodiesterase 1 (GDE-1) but high levels of the degrading enzyme fatty acid amidohydrolase (FAAH) that increases with maturation. Finally, cells from both regions show similar levels of CB1 receptor and GPR55, but spinal cord-derived cells show significantly higher levels of transient receptor potential cation channel V1 (TRPV1) and CB2. Overall, our results show that the majority of the ECS components could be targeted in OPCs and OLs from both the spinal cord and brain, but regional heterogeneity has to be considered for DAGLA, MGLL, ABHD6, ABHD12, GDE1, CB2, or TRPV1.

CAPN10 alleles modify laryngeal cancer risk in the Spanish population.

AIMS: Laryngeal carcinoma is a common upper respiratory tract cancer with different environmental and genetic factors involved in its development. To date, CAPN10 has been found to be extensively associated with hyperinsulinaemia and type 2 diabetes mellitus, by different groups. In addition, some reports have shown evidence that hyperinsulinaemia exerts a protective effect on laryngeal cancer risk. On the other hand, low circulating levels of IGF-1 have been recently found in patients with laryngeal carcinoma. Our objective was to examine the contribution of CAPN10 alleles to the development of laryngeal cancer. METHODS: Cases and controls were recruited from central and southern Spain. Genotypes were determined using pyrosequencing technology. We analysed CAPN10 UCSNP-44, -43, -19, and -63 allelic distribution in 218 unrelated laryngeal cancer patients and 606 controls from the general population. RESULTS: We found that the UCSNP-44 allele-C is significantly under-represented among patients with laryngeal cancer (OR=0.685, p=0.02). CONCLUSION: These results indicate that some CAPN10 alleles may be exerting a protective effect on laryngeal cancer risk in the Spanish population.