Rhinology最新文献

Background: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus.

Methods: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses.

Results: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each.

Conclusions: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms.

Methods: A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed.

Results: In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-β, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-β1 and CCL-24 production, contributing to CRSwNP recurrence.

Conclusions: Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

microRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate post-transcriptional gene expression. Accumulating evidence suggests their involvement in regulating various biological and pathological processes, including inflammation. Studies have revealed distinct expression patterns of miRNAs in Chronic Rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps (1). Specifically, miR-155 and miR-21 have been observed to be upregulated in CRSwNP, increasing and attenuating the expression of pro-inflammatory cytokines, respectively (2,3). Conversely, the downregulation of miR-34, miR-449, and members of the miR-200 family has been associated with impaired ciliogenesis and the regulation of epithelial-mesenchymal transition, respectively (4,5). Nonetheless, the direct role of miRNAs in CRSwNP is still being investigated.

Background: There is no known predictor for olfactory function recovery with dupilumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP). This study assessed whether patient-reported recovery of olfactory function on oral corticosteroids (OCS) is a prognostic factor.

Methods: Retrospective analysis of pre-biological OCS-responsiveness on olfactory functioning (OCS-responsive or OCS-unresponsive; OCS-r and OCR-u, respectively) as predictor for olfactory functioning after 6 months of dupilumab therapy for severe CRSwNP.

Results: 212 CRSwNP patients treated with dupilumab were divided between OCS-r (reported improvement of olfactory function with OCS before dupilumab treatment, n = 152), and OCS-u (OCS-unresponsive; no such improvement, n = 60). Olfactory function was tested with Sniffin's Sticks Identification Test (12 pens; SSIT-12). At baseline, both groups had a median SSIT-12 score of 3 / 12 indicating anosmia. Hyposmia and normosmia rates were also comparable (5.9% and 3.3% in OCS-r, respectively; 5.0% and 1.7% in OCS-u, respectively). After 6 months of dupilumab treatment, OCS-r showed higher olfactory scores (median SSIT-12: 8/12; 52.6% hyposmia and 17.8% normosmia) than OCS-u (median SSIT-12: 5/12; 31.7% hyposmia and 3.3% normosmia). The positive predictive value of OCS-responsiveness on scoring <7 (normosmia/hyposmia) on the SSIT-12 after 6 months of dupilumab treatment was 70.4%. Conversely, the negative predictive value of OCS-unresponsiveness on scoring <7 (anosmia) on the SSIT-12 after 6 months of dupilumab treatment was 65.0%.

Conclusion: Patients who report olfactory function improvement on OCS have a higher chance of recovery of olfactory function during the first six months of treatment with dupilumab than patients who do not.

Background: This study aimed to determine how nasal airflow measures and trigeminal function vary among patients with chronic rhinosinusitis (CRS) versus healthy controls and whether these measures are correlated with subjective nasal obstruction (SNO), olfactory function, and CRS control.

Methodology: Participants included CRS patients and healthy controls. After a structured medical history, nasal airflow (peak nasal inspiratory flow [PNIF]; active anterior rhinomanometry [AAR]), trigeminal function (trigeminal lateralization test, CO2 sensitivity), and olfactory "Sniffin's Sticks" odor identification test) tests were performed. SNO ratings were also obtained.

Results: Sixty-nine participants were included (37 men, 32 women, mean age 51 years). There was no significant difference for objective nasal airflow between patients and controls, but CRS patients had worse SNO, trigeminal function, and olfaction compared to controls. SNO, but not objective nasal airflow tests, was negatively correlated with CO2 sensitivity and odor identification.

Conclusion: The perception of nasal obstruction does not only depend on nasal airflow, but may also be modulated by trigeminal function and other factors. Thus, the role of objective nasal airflow measures as a sole method of functional nasal obstruction assessment in CRS remains limited.

Background: Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion commonly occurring in the nasal cavity and sinuses. It is often accompanied by nasal polyps (NP). While the histological features of these two conditions have been studied, there is limited knowledge about their differences in the underlying immunopathology.

Methods: Nasal tissue specimens were collected from 8 patients with concurrent REAH and NP and 10 controls. The expression levels of inflammatory cytokines, tight junctions (TJ), and epithelial-mesenchymal transition (EMT)-related factors in the tissues were analyzed. The mRNA expression of the aforementioned factors was measured using qRT-PCR, while the expression of TJ and EMT-related proteins was analyzed through Western blotting and immunohistochemistry.

Results: Compared to the control group, levels of inflammatory cytokines (IFN-α, IL-5, IL-17A, IL-31, IL-33, and TNF-α) and EMT-related factors (α-SMA, COL1A1, MMP9, TGF-β1, and Vimentin) were significantly increased in both REAH and NP tissues. Conversely, E-Cadherin and TJ-related factors (Claudin-4 and Occludin) significantly decreased. When comparing REAH with NP, it was observed that the expression of IL-4, IL-5, and IL-33 was lower in REAH, while TNF-ɑ; was higher. Regarding TJ-related factors, the expression of Occludin was lower in REAH. Furthermore, in terms of EMT-related factors, except for E-Cadherin, the expressions of ɑ-SMA, COL1A1, CTGF, MMP9, TGF-β11, and Vimentin were higher in REAH.

Conclusion: REAH and NP exhibit different immunopathological mechanisms. NP demonstrates a more severe inflammatory response, whereas REAH is characterized by a more pronounced TJ and EMT breakdown than NP.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently leads to olfactory dysfunction. This study aimed to assess the impact of dupilumab on CRSwNP patients, focusing on olfactory outcomes and potential correlations with other clinical factors.

Methods: CRSwNP patients eligible for dupilumab therapy received subcutaneous Dupixent® injections every two weeks (300mg/2ml dupilumab). The 12-item Sniffin' Sticks Test (SST-12), fractional exhaled nitric oxide (FeNO) and Nasal Polyp Score (NPS) were assessed at baseline and after one, three, and six months. Patients also completed the Sino-Nasal Outcome Test (SNOT-22) weekly.

Results: 26 CRSwNP patients were included. After one month, dupilumab led to substantial reductions in FeNO, SNOT scores, andNPS, whereas SST-12 scores improved significantly only after three months. A shift toward normosmia occurred, with 81% achieving normosmia after six months, and a drop in anosmia prevalence to 9.5%. Significant negative correlations between olfaction (SST-12) and polyp severity (NPS) at baseline and after six months were found, while no significant correlations were observed between SST-12 and FeNO or SNOT scores. Age did not correlate with olfaction.

Conclusions: Dupilumab demonstrated efficacy in restoring olfaction in CRSwNP patients. Reaching normosmia in over 80% ofpatients after six months of treatment underscores the drug's effectiveness in managing this challenging symptom.

Background: The introduction of CFTR modulators has changed the landscape in the treatment of cystic fibrosis (CF) and early case series have shown improvements in sinonasal outcomes in this patient population.

Methodology: A real-word data study was performed to evaluate the impact of dual therapy with tezacaftor/ivacaftor (TEZ/IVA) and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CF-related chronic rhinosinusitis (CRS), by comparing subjective and objective outcome measures at baseline, 12 months after treatment with TEZ/IVA and six months after treatment with ELX/TEZ/IVA.

Results: In total, 43 CF patients, with a mean age of 32 years, were included. After triple therapy, significant improvements in overall visual analogue scale, SNOT-22, Lund Kennedy, nasal polyps, and Lund-Mackay scores were observed, whereas no beneficial effect could be seen in patients treated with dual therapy. Bacterial upper airway colonization did not differ pre- and postmodulator therapy in the present study. The number of responders to dual and triple therapy is 23.8% and 63.2% of the patients, respectively.

Conclusions: Triple therapy with ELX/TEZ/IVA is superior to dual therapy with TEZ/IVA in the treatment of CF-CRS, as significantly reduced sinonasal complaints, nasal endoscopy and CT scores were observed after triple therapy, whereas this was not the case for dual therapy.

Background: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated.

Methods: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments.

Results: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3’-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity.

Conclusions: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

Objective: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss.

Methods: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores.

Results: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function.

Conclusion: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.