Delivery of Topical Drugs to the Olfactory Cleft.

Olfactory dysfunction affects approximately 20% of the population globally, with incidence increasing over the age of 60. The pathophysiology is complex, not yet fully understood, and depends on many factors, including the underlying cause. Despite this, the present literature on olfaction is limited due to significant heterogeneity in methodological approaches. This has resulted in limited effective treatments available for olfactory dysfunction. Medications for olfactory dysfunction can be administered locally (directly to the olfactory epithelium) or systemically (orally or intravenously). Currently, there are various methods for local drug delivery to the olfactory epithelium (nasal drops, nasal sprays, atomisers, pressured meter-dosed inhalers, rinses, and exhalation delivery systems). The aims of this review are to summarise the different methods of drug delivery to the olfactory cleft, evaluate the current literature to assess which method is the most effective in delivering drugs to the olfactory epithelium, and review the medications currently available to treat olfactory dysfunction topically. Going forward, further research is required to better establish effective methods of drug delivery to the olfactory epithelium to treat smell disorders.

Assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.

Purpose of review: To provide a detailed overview of the assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms. Recent findings: COVID-19-related olfactory dysfunction can have a detrimental impact to the quality of life of patients. Prior to the COVID-19 pandemic, olfactory and taste disorders were a common but under-rated, under-researched and under-treated sensory loss. The pandemic has exacerbated the current unmet need for accessing good healthcare for patients living with olfactory disorders and other symptoms secondary to COVID-19. This review thus explores the associations that COVID-19 has with psychological, neuropsychiatric, and cognitive symptoms, and provide a framework and rationale for the assessment of patients presenting with COVID-19 olfactory dysfunction. Summary: Acute COVID-19 infection and long COVID is not solely a disease of the respiratory and vascular systems. These two conditions have strong associations with psychological, neuropsychiatric, and cognitive symptoms. A systematic approach with history taking and examination particularly with nasal endoscopy can determine the impact that this has on the patient. Specific olfactory disorder questionnaires can demonstrate the impact on quality of life, while psychophysical testing can objectively assess and monitor olfaction over time. The role of cross-sectional imaging is not yet described for COVID-19-related olfactory dysfunction. Management options are limited to conservative adjunctive measures, with some medical therapies described.

Systematic Review of Protein Biomarkers in Adult Patients With Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. OBJECTIVE: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. METHODS: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. RESULTS: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. CONCLUSION: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid.We registered this study in PROSPERO (CRD42022302787).

Establishing UK research priorities in smell and taste disorders: A James Lind alliance priority setting partnership.

OBJECTIVES: To determine the top 10 research priorities in Smell and Taste Disorders (SATD). DESIGN: After steering group was established, an electronic survey was disseminated to determine the list of questions. After removing out-of-scope responses, the remainder were consolidated to create summary questions. A literature search was conducted to remove already answered questions. A second survey was used to determine the top questions that formed the subject of final debate at a workshop attended by clinicians and patients to determine the top 10 priorities. SETTING: A James Lind Alliance Priority Setting Partnership (JLAPSP) was established by FifthSense to identify the top 10 research questions in SATDs in the United Kingdom. PARTICIPANT: All stakeholders in SATDs (patients, healthcare professionals, family, carers, researchers). MAIN OUTCOME MEASURES: Final 10 research priorities. RESULTS: The 665 respondents to the initial survey provided 1698 research questions. Thirteen were out-of-scope and removed; remaining 1685 were then consolidated to form 147 summary questions. Following literature search and discussion with the steering group, 37 questions remained for the second survey, which 235 people responded. The top ten priorities agreed upon in the workshop covered themes of improved understanding of pathophysiologlogy, improving health services, and managing long-term effects of smell/taste disorders. The most important research question agreed was "How can we further our understanding of the mechanism of disease in the nerve pathways that affect smell and taste disorders, including where parosmia and phantosmia exist." CONCLUSION: We report the top 10 research priorities in smell and taste disorders. These priorities will now empower researchers to secure research funding and provide the basis of the FifthSense research hub.

Single dose of BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces neutralising antibody and polyfunctional T-cell responses in patients with chronic myeloid leukaemia.

Patients receiving targeted cancer treatments such as tyrosine kinase inhibitors (TKIs) have been classified in the clinically extremely vulnerable group to develop severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including patients with chronic myeloid leukaemia (CML) taking TKIs. In addition, concerns that immunocompromised individuals with solid and haematological malignancies may not mount an adequate immune response to a single dose of SARS-CoV-2 BNT162b2 (Pfizer-BioNTech) vaccine have been raised. In the present study, we evaluated humoral and cellular immune responses after a first injection of BNT162b2 vaccine in 16 patients with CML. Seroconversion and cellular immune response before and after vaccination were assessed. By day 21 after vaccination, anti-Spike immunoglobulin G was detected in 14/16 (87·5%) of the patients with CML and all developed a neutralising antibody response [serum dilution that inhibits 50% infection (ID50 ) >50], including medium (ID50 of 200-500) or high (ID50 of 501-2000) neutralising antibodies titres in nine of the 16 (56·25%) patients. T-cell response was seen in 14/15 (93·3%) evaluable patients, with polyfunctional responses seen in 12/15 (80%) patients (polyfunctional CD4+ response nine of 15, polyfunctional CD8+ T-cell response nine of 15). These data demonstrate the immunogenicity of a single dose of SARS-CoV-2 BNT162b2 vaccine in most patients with CML, with both neutralising antibodies and polyfunctional T-cell responses seen in contrast to patients with solid tumour or lymphoid haematological malignancies.