Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Radiological Versus Clinical 1-Year Outcomes of Dupilumab in Refractory CRSwNP: A Real-Life Study.

OBJECTIVE: To provide real-life evidence on long-term radiological changes in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab, and to assess possible differences between radiological and clinical results in terms of endoscopic findings and Patient-Reported-Outcomes (PROs). METHODS: Consecutive patients treated with dupilumab for recalcitrant CRSwNP were required to undergo CT scan at baseline (T0) and after 12 (T1) since first administration. A group of patients also performed CT scan at 52 weeks (T2) to assess long-term outcomes. At each timepoint, patients underwent nasal endoscopy, assessment of Nasal-Polyp-Score (NPS), Lund-Kennedy-Score (LKS), and had to fill in the 22-item Sinonasal-Outcome-Test (SNOT-22) and Visual-Analogue-Scales (VAS) for sinonasal symptoms. RESULTS: In fifty-three included patients, from T0 to T1 we detected a significant reduction in mean Lund-Mackay score (LM), PROs (SNOT-22, VAS) and endoscopic (NPS, LKS) scores (p < 0.05). In the subset of patients that reached T2 (n = 30), compared to T1, we observed a further significant decrease in mean LM, SNOT-22, VAS, and NPS scores, but not in LKS (p = 0.420). At T1, the highest improvement was observed in PROs (SNOT-22: 56.26%), and polyp size (NPS: 49.83%). Conversely, between T1 and T2, sinus opacification was shown to be the most improved outcome (LM: 36.86%). CONCLUSIONS: Our experience showed that poorly controlled CRSwNP patients treated with dupilumab experienced significant improvement in radiologic, endoscopic and clinical disease severity. While in the initial 3 months, PROs garnered attention for showing earlier effectiveness, radiological outcomes revealed sustained and gradual efficacy in a longer term. LEVEL OF EVIDENCE: Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 134:2626-2633, 2024.

Mast Cells in Upper and Lower Airway Diseases: Sentinels in the Front Line.

Mast cells (MCs) are fascinating cells of the innate immune system involved not only in allergic reaction but also in tissue homeostasis, response to infection, wound healing, protection against kidney injury, the effects of pollution and, in some circumstances, cancer. Indeed, exploring their role in respiratory allergic diseases would give us, perhaps, novel therapy targets. Based on this, there is currently a great demand for therapeutic regimens to enfeeble the damaging impact of MCs in these pathological conditions. Several strategies can accomplish this at different levels in response to MC activation, including targeting individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth, or inducing mast cell apoptosis. The current work focuses on and summarizes the mast cells' role in pathogenesis and as a personalized treatment target in allergic rhinitis and asthma; even these supposed treatments are still at the preclinical stage.

Evolution in Endoscopic Sinus Surgery: The Adjuvant Role of Reboot Surgery in Patients with Uncontrolled Nasal Symptoms of Eosinophilic Granulomatosis with Polyangiitis.

PURPOSE: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. METHODS: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. RESULTS: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. CONCLUSIONS: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.

Middle meatus nasal cytology compared to inferior turbinate cytology in non allergic rhinitis.

PURPOSE: Non allergic rhinitis (NAR) comprises different clinical definitions and phenotypes, including non inflammatory non allergic (NINAR) and cellular inflammatory forms. Nasal cytology, usually performed by scraping the inferior turbinate, is a non invasive, cheap and point-of-care tool to distinguish among the different NAR phenotypes, but still a relevant proportion of patients evaluated by nasal cytology receive a non precise definition of NAR phenotype. We hypothesize that collecting nasal cytology samples from middle meatus could increase the diagnostic accuracy. METHODS: Consecutive patients with chronic rhinitis without evidence of allergic sensitization were assessed for nasal cytology by means of scraping both the inferior turbinate and the middle meatus (lateral-inferior wall of the middle turbinate). RESULTS: 107 consecutive patients with NAR were enrolled in the study. According to inferior turbinate cytology, 42.1% were defined as affected by NINAR, 2.8% by bacterial rhinitis, 10.3% by non allergic rhinitis with eosinophils (NARES), 15.0% non allergic rhinitis with neutrophils (NARNE), 19.6% non allergic rhinitis with mast-cells (NARMA) and 10.3% non allergic rhinitis with eosinophils and mast-cells (NARESMA). Middle meatus cytology was in accordance with inferior turbinate cytology in only 37.6% of cases. Eosinophils and mast-cells were detectable more frequently in middle meatus samples (49.5% vs 19.6%, p < 0.01, 59.8% vs 29.9%, p < 0.01, respectively). 93.3% of NINAR patients received an inflammatory NAR phenotype at middle meatus cytology: 26.7% NARES, 24.4% NARNE, 31.1% NARMA and 11.1% NARESMA. CONCLUSION: Middle meatus cytology is more reliable than inferior turbinate cytology in phenotyping patients with NAR. Our study strengthen that nasal cytology should be implemented in clinical practice collecting samples at the middle meatus level.

Outcomes of Non-Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience.

OBJECTIVE: The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery. METHODS: A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries. RESULTS: Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p = 0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p = 0.010, p = 0.002, p = 0.016, respectively); RFS difference resulted significant (log-rank test = 4.16; p = 0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p = 0.001), as well as VAS scores (p = 0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot. CONCLUSIONS: The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure. LEVEL OF EVIDENCE: 4: According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 133:1584-1589, 2023.

Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.

Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Results: Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Conclusions: Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.