Virtual voice clinics in the COVID-19 era: have they been helpful?

PURPOSE: In response to the coronavirus pandemic, a tertiary combined Laryngology-Speech Therapy voice clinic was converted to a wholly virtual clinic, with consultations carried out via telephone or video. The aim of our mixed method study was to assess (a) how effective are virtual clinics vs face-to-face clinics in progressing patients' care and (b) what is patient satisfaction with virtual consultation methods. METHODS: Analysis of clinic data from patient databases for both virtual and face-to-face clinics was carried out. A patient satisfaction survey was carried out by 75 of the patients who had attended virtual clinics. RESULTS: There was statistically a significant difference (p value < 0.01) in the proportion of patients prescribed medical therapy, referred for Speech and Language Therapy (SALT) or listed for surgery in the virtual clinic by comparison to the face-to-face clinic. 75 patients completed the questionnaire. 98% of patients were satisfied overall with the virtual method of consultation. 84% believed they would still benefit from face-to-face review. 83% would like the option of a virtual type of clinic in the future. CONCLUSION: Our data clearly demonstrates that face-to-face clinics are superior to virtual clinics, with almost no patients progressed to surgery in virtual consultations. Despite this, virtual methods are still valuable, and many patients have meaningful progression of care. In current circumstances, patients have very high satisfaction with virtual consultations and certain groups have been identified as particularly benefiting. Going forward, an ideal clinic may be a hybrid of face-to-face and virtual appointments as clinically indicated.

Vitamin D Counteracts an IL-23-Dependent IL-17A+IFN-γ+ Response Driven by Urban Particulate Matter.

Urban particulate matter (UPM) air pollution and vitamin D deficiency are detrimentally associated with respiratory health. This is hypothesized to be due in part to regulation of IL-17A, which UPM is reported to promote. Here, we used a myeloid dendritic cell (DC)-memory CD4+ T cell co-culture system to characterize UPM-driven IL-17A+ cells, investigate the mechanism by which UPM-primed DCs promote this phenotype, and address evidence for cross-regulation by vitamin D. CD1c+ myeloid DCs were cultured overnight with or without a reference source of UPM and/or active vitamin D (1,25[OH]2D3) before they were co-cultured with autologous memory CD4+ T cells. Supernatants were harvested for cytokine analysis on Day 5 of co-culture, and intracellular cytokine staining was performed on Day 7. UPM-primed DCs increased the proportion of memory CD4+ T cells expressing the T helper 17 cell (Th17)-associated cytokines IL-17A, IL-17F, and IL-22, as well as IFN-γ, granulocyte-macrophage colony-stimulating factor, and granzyme B. Notably, a large proportion of the UPM-driven IL-17A+ cells co-expressed these cytokines, but not IL-10, indicative of a proinflammatory Th17 profile. UPM-treated DCs expressed elevated levels of il23 mRNA and increased secretion of IL-23p40. Neutralization of IL-23 in culture reduced the frequency of IL-17A+IFN-γ+ cells without affecting cell proliferation. 1,25(OH)2D3 counteracted the UPM-driven DC maturation and inhibited the frequency of IL-17A+IFN-γ+ cells, most prominently when DCs were co-treated with the corticosteroid dexamethasone, while maintaining antiinflammatory IL-10 synthesis. These data indicate that UPM might promote an inflammatory milieu in part by inducing an IL-23-driven proinflammatory Th17 response. Restoring vitamin D sufficiency may counteract these UPM-driven effects without obliterating important homeostatic immune functions.

Effects of coronavirus disease-2019 on voice: our experience of laryngeal complications following mechanical ventilation in severe coronavirus disease-2019 pneumonitis and review of current literature.

PURPOSE OF REVIEW: Dysphonia has been described as a major symptom of coronavirus disease-2019 (COVID-19). A literature review examining this topic was undertaken and is presented here, combined with insights from our experience in managing patients with laryngeal complications following mechanical ventilation for severe COVID-19 pneumonitis. RECENT FINDINGS: Naunheim et al. reported that patients who are most at risk of needing intubation with COVID-19 disease are those with patient-specific risk factors and these are at an increased risk for subsequent laryngotracheal injury following intubation (1). In our cohort of 105 patients referred with laryngological symptoms postintubation for COVID-19 pneumonitis, 40% presented as urgent reviews, of which almost half had severe postintubation complications requiring surgery. Perceptual voice ratings and patient-reported voice ratings varied widely, but there was no significant change in voice scores postoperatively. The reflux symptom index (RSI) scores did improve significantly (p = 0.0266). The need for surgery was associated with the presence of comorbidities for instance hypertension, diabetes and obesity in our cohort. This is in support of reported association of comorbidity as a risk factor for intubation and subsequent development of postintubation airway complications. SUMMARY: Dysphonia following COVID-19 infection may have multiple causes. Literature reports demonstrate intubation injury, sensory neuropathy, and postviral neuropathy are associated with voice changes. Our personal experience has confirmed postintubation injury markedly affects glottic function with resultant dysphonia attributable to scar formation, posterior glottic stenosis, granulation and subglottic stenosis. Frequent surgical intervention is required for airway patency and may have short-term further deleterious effects on phonation, although in our cohort this is not statistically significant analysing Grade, Roughness, Breathiness, Asthenia, Strain, Voice Handicap Index-10 or Airway, Voice, Swallow scores. Maximal antireflux medications and advice statistically improved RSI scores postoperatively.

B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma.

In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires are characterized by both IgD-only B cells and others undergoing class switch recombination, with restriction of the antibody repertoire distinct in asthmatics compared with controls. We conclude that B cells and plasma cells migrate freely throughout the respiratory tract and exhibit distinct antibody repertoires in health and disease.

The allergic march from Staphylococcus aureus superantigens to immunoglobulin E.

Staphylococcus aureus is a commensal bacterium in the respiratory tract mucosa of most people and infects the skin of atopic dermatitis patients. This might imply a symbiotic relationship between host and bacterium or a standoff between bacterial infection and the host immune system. But superantigens produced by S. aureus in these locations are of particular interest because they are strongly implicated in the pathogenesis of allergic disorders and airway disease. They appear to act locally in these conditions by stimulating polyclonal T cell and B cell proliferation and driving somatic hypermutation, class switching to immunoglobulin (Ig) E and the production of allergen-specific IgE in mucosal B cells. IgE antibodies directed against the superantigens ('superallergens') themselves engender chronic inflammation and the persistent sensitization to conventional allergens of mast cells and antigen-presenting cells in mucosal tissues in atopic dermatitis, rhinitis and asthma. Moreover, S. aureus superantigens inhibit the activity of T regulatory cells that normally control inflammation, and generate a state of steroid resistance that confounds treatment of allergic disorders and airway disease.

Sudden sensorineural hearing loss and antiphospholipid syndrome.

The antiphospholipid syndrome is the association between the presence of antiphospholipid antibodies, thrombosis and/or pregnancy morbidity and mortality. This report presents two cases of antiphospholipid antibodies and sensorineural hearing loss and discusses the probable causative link. We recommend that patients presenting with sudden sensorineural hearing loss are investigated for evidence of antiphospholipid antibodies. Life long anticoagulation is necessary to prevent life threatening thrombotic or thromboembolic events.

Functional plasticity of human respiratory tract dendritic cells: GM-CSF enhances T(H)2 development.

BACKGROUND: Dendritic cells within the human respiratory mucosa (RTDCs) are proposed to initiate immune responses to foreign antigens. Their capacity to polarize T-cell responses, however, has not been investigated. OBJECTIVE: To compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to phenotype, cytokine production, capacity to polarize T-cell responses, and effects of exposure to the pleiotropic cytokine, GM-CSF. METHODS: CD1a(+) RTDCs and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic rhinitis and peripheral blood of healthy individuals, respectively. In some experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were compared. The phenotype of DC was examined by flow cytometry and cytokine production by cytometric bead array. DCs were cocultured with allogeneic naive CD4(+) T cells, and cytokine production was determined by immunophenotyping, cytometric bead array, and ELISA. RESULTS: Both RTDCs and PBDCs exhibited an immature phenotype, but RTDCs expressed lower levels of MHC class II antigen. Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM-CSF promoted a T(H)1 response. CONCLUSION: This report emphasizes the importance of studying tissue-derived primary DCs, demonstrates functional plasticity of RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate T(H)2 responses in the airways.

Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis.

BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE VH genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown. OBJECTIVE: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA VH use in the same biopsy specimens and also those from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a significantly increased frequency of IgE and IgA VH5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the VH5 sequences were in framework region 1. The hotspots and a conserved VH5-specific framework residue form a tight cluster on the surface of VH5. CONCLUSION: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.