Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

OBJECTIVES: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. METHODS: We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. RESULTS: 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. CONCLUSIONS: BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis.

BACKGROUND: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. METHODS: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. RESULTS: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan-Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. CONCLUSIONS: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed.

Insights into the molecular triggers of parosmia based on gas chromatography olfactometry.

Background: Parosmia is a debilitating condition in which familiar smells become distorted and disgusting, with consequences for diet and mental health. It is a feature of post-infectious olfactory loss, particularly resulting from COVID-19. There is currently little understanding of its pathophysiology, and the prevailing hypothesis for the underlying mechanism is aberrant growth of regenerating olfactory sensory neurons after damage. Methods: We use gas-chromatograph olfactometry to individually present components of a complex olfactory mixture as a rapid screening tool for assessment of both quantitative and qualitative olfactory dysfunction in those with and without parosmia. This allows them to report the associated sensory effects and to identify those molecules which are altered or parosmic in nature. Results: Here we show 15 different molecular triggers of this symptom. These trigger molecules are common to many in the parosmic volunteer group and share certain characteristics such as extremely low olfactory threshold and common molecular structure. Conclusions: We posit that specific highly odour-active molecules are the cause of the parosmic symptom in most cases and initiate the sense of disgust, suggesting that parosmia is, at least in part, a receptor-level phenomenon.

Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression.

BACKGROUND: Chronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma. METHODS: Hospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow-up measures were collected 16 weeks after omalizumab treatment. RESULTS: HADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS-anxiety scores. Abnormal HADS-depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test-22 (SNOT-22) versus HADS total was r = 0.59 p < 0.0001, HADS-anxiety r = 0.56 p < 0.0001 and HADS-depression r = 0.49 p < 0.0001. Omalizumab improved anxiety in CRS (p < 0.0001) regardless of nasal polyp status (CRSwNP p = 0.0042 and CRSsNP p = 0.0078). Depression scores did not improve in either group. SNOT-22 (p = 0.0006), asthma control questionnaire-7 (p = 0.0019) and mini-asthma quality of life questionnaire including emotional function (p = 0.0003 and p = 0.0009, respectively) all improved in both subgroups. CONCLUSION: In CRS and asthma, anxiety scores but not depression improved after omalizumab treatment. Anxiety may be closely related to airway disease severity, but depression may be independent of airway disease itself. If so, a separate mental health care pathway is needed for CRS patients with depression.

Dupilumab: Clinical Efficacy of Blocking IL-4/IL-13 Signalling in Chronic Rhinosinusitis with Nasal Polyps.

In September 2019, The Lancet published details of two large Phase III double-blind placebo-controlled studies (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52) confirming the clinical efficacy of the biologic dupilumab in simultaneously blocking both IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps (CRSwNP). The studies demonstrated that dupilumab (Dupixent®, Sanofi and Regeneron) 300mg subcutaneously administered was clinically effective when added for patients with moderate to severe CRSwNP already maintained on the standard intranasal steroid mometasone furoate. Duration of treatment ranged from injections either 2 weekly for 24 weeks (SINUS-24) or every 2 weeks for 52 weeks or finally every 2 weeks for 24 weeks stepping down thereafter to every 4 weeks for a further 28 weeks (SINUS-52). Rapid improvements in all important parameters of disease burden were seen with such improvement maintained even where the frequency of injections was decreased. In patients with co-existent asthma, lung function and asthma control scores improved. This is consistent with the one airway hypothesis of shared T2 inflammatory programmes driving both disease syndromes. The studies formed the basis for FDA registration and clinical launch in the US, and EMA approval in Europe. Dupilumab presents a significant new treatment option in an area of urgent unmet therapeutic need in CRSwNP. Should dupilumab prove to be as effective in the real-life clinical environment as it has been in the studies, then a paradigm shift from sinonasal surgery to medical treatment of CRSwNP may need to occur in the ENT community. Questions in relation to best patient selection, combined upper and lower airway therapeutic pathways, long-term safety along with health economics and cost constraints ought now to be addressed.

Allergen-induced asthma, chronic rhinosinusitis and transforming growth factor-ß superfamily signaling: mechanisms and functional consequences.

Introduction: Often co-associated, asthma and chronic rhinosinusitis (CRS) are complex heterogeneous disease syndromes. Severity in both is related to tissue inflammation and abnormal repair (termed remodeling). Understanding signaling factors that can modulate, integrate the activation, and regulation of such key processes together is increasingly important. The transforming growth factor (TGF)-ß superfamily of ligands comprise a versatile system of immunomodulatory molecules that are gaining recognition as having an essential function in the immunopathogenesis of asthma. Early data suggest an important role in CRS as well. Abnormal or dysregulated signaling may contribute to disease pathogenesis and severity.Areas covered: The essential biology of this complex family of growth factors in relation to the excess inflammation and remodeling that occurs in allergic asthma and CRS is reviewed. The need to understand the integration of signaling pathways together is highlighted. Studies in human airway tissue are evaluated and only selected key animal models relevant to human disease discussed given the highly context-dependent signaling and function of these ligands.Expert opinion: Abnormal or dysregulated TGF-ß superfamily signaling may be central to the excess inflammation and tissue remodeling in asthma, and possibly CRS. Therefore, the TGF-ß superfamily signaling pathways represent an emerging and attractive therapeutic target.

Epistaxis due to traumatic internal carotid artery aneurysm.

Epistaxis due to internal carotid artery (ICA) trauma is uncommon, and that due to aneurysm of the artery is rarer still. Most cases result in fatality due to severe, uncontrolled blood loss. The ICA is vulnerable to oropharyngeal trauma as it ascends beside the lateral pharyngeal wall. We describe a case of an 11-month-old girl who sustained oropharyngeal wall trauma from the handle of a wooden spoon. After a characteristic latent period of several days, upper airway obstruction occurred due to a right parapharyngeal mass, which extended inferiorly to the level of the larynx. Angiography confirmed a large dissecting ICA aneurysm. This was treated successfully by radiological coil occlusion.