Upper Airway Complications in COVID-19: A Case Series.

Prolonged intubation is associated with several complications leading to upper airway obstruction, including tracheal stenosis and tracheomalacia. Tracheostomy may potentially decrease the risk of tracheal injury in patients with upper airway obstruction. The ideal timing to perform tracheostomy remains controversial. Prolonged intubations were particularly common during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to present a series of five cases of upper airway complications in patients who underwent mechanical ventilation in the setting of COVID-19 and discuss their clinical aspects, risk factors, and therapeutic strategies.

Cricothyroidotomy Simulator: A Makerspace and Augmented Reality Approach

A cricothyroidotomy is an incision made on the cricothyroid membrane at its midline to create an airway for oxygenation and ventilation. Cricothyroidotomy is a complex procedure involving motor, psychological, and decision-making skills, amply used during the COVID-19 pandemic. This procedure requires extensive training, and simulators facilitate teaching advanced airway management techniques to health care professionals. However, upper airway simulators are expensive and limited to specialized facilities inaccessible during the COVID-19 pandemic when in-laboratory practices shifted to online synchronous and asynchronous teaching. Such a scenario sparked interest in makerspace technologies for creating cost-effective simulators. This paper presents the prototyping of a cricothyroidotomy simulator through a Design Thinking approach to ideate a cost-effective solution that contains all 3D printed structures properly representing the real anatomical parts needed for the procedure. Additionally, we propose an augmentation of the 3D printed model employing Augmented Reality (AR) to enhance how information about the procedure can be accessed without relying on traditional instruction materials. Our preliminary results have led to a makerspace cricothyrotomy simulator used in training sessions in conferences and workshops and the prototyping of an AR complementary tool. © 2022 IEEE.

Vocal Cord Dysfunction During the COVID-19 Pandemic.

BACKGROUND: Vocal cord dysfunction is an upper-airway disorder characterized by exaggerated and transient glottic constriction causing respiratory and laryngeal symptoms. Common presentation is with inspiratory stridor often in the context of emotional stress and anxiety. Other symptoms include wheezing (which may be on inspiration), frequent cough, choking sensation, or throat and chest tightness. This is seen commonly in teenagers, particularly in adolescent females. The COVID-19 pandemic has been a trigger for anxiety and stress with an increase in psychosomatic illness. Our objective was to find out if the incidence of vocal cord dysfunction increased during COVID-19 pandemic. METHODS: We performed a retrospective chart review of all the subjects with a new diagnosis of vocal cord dysfunction who were seen at the out-patient pulmonary practice at our children's hospital between January 2019-December 2020. RESULTS: The incidence of vocal cord dysfunction in 2019 was found to be 5.2%, (41/786 subjects seen) compared to 10.3% (47/457 subjects seen) in 2020, which is a nearly 100% increase in incidence (P < .001). CONCLUSIONS: It is important to recognize that vocal cord dysfunction has increased during the COVID-19 pandemic. In particular, physicians treating pediatric patients, as well as respiratory therapists, should be aware of this diagnosis. It is imperative to avoid unnecessary intubations and treatments with bronchodilators and corticosteroids as opposed to behavioral and speech training to learn effective voluntary control over the muscles of inspiration and the vocal cords.

Upper airway dimensions and the skeletal parameters in orthodontic patients who developed moderate-severe COVID-19 symptoms during the pandemic.

BACKGROUND: Large airway dimensions are associated with a rapid decline in the lung function and a higher risk of hospitalization. Therefore, the airway dimensions of healthy subjects who tested positive for coronavirus disease 2019 (COVID-19) may be associated with the severity of COVID-19 symptoms. OBJECTIVES: The objectives of this study were to measure the upper airway dimensions and the craniofacial skeletal parameters in patients who tested positive for COVID-19, to compare the upper airway dimensions and the craniofacial skeletal parameters between patients who developed no/mild symptoms and those with moderate-severe COVID-19 symptoms, and to assess any association of the skeletal relationships (anteroposterior (AP) and vertical) and the upper airway dimensions with the severity of COVID-19 symptoms in adult subjects. MATERIAL AND METHODS: A total of 204 orthodontic patients who tested positive for COVID-19 were evaluated. Of these, only 137 met the inclusion criteria. The sample was further subdivided into 2 groups based on the severity of symptoms: cases (moderate-severe symptoms; n = 56); and controls (asymptomatic/ mild symptoms; n = 81). The upper airway dimensions and the skeletal parameters were measured on lateral cephalograms. The nonparametric Mann-Whitney U test was used to detect differences between the cases and the controls. Binary logistic regression analysis was used to evaluate the association between the studied variables and the severity of symptoms. RESULTS: The cases had a reduced lower face height (LFH) and a reduced perpendicular distance from the hyoid bone to the line connecting the anteroinferior limit of the 3rd cervical vertebra (C3) and the retrognathion point (RGN) (HH1) as compared to the controls. Regression analysis revealed a significant association of LFH (p = 0.013), the vertical airway length (VAL) (p = 0.002) and HH1 (p = 0.021) with the severity of COVID-19 symptoms. CONCLUSIONS: The types of malocclusion were similar in the cases and the controls. Patients with reduced LFH and VAL, and a superiorly positioned hyoid bone in relation to the mandible developed more severe COVID-19 symptoms.

Smartphone-based follow-up of upper airway symptoms in head and neck cancer survivors one year after radiation therapy.

BACKGROUND: Improvements in treatment of head-and-neck cancer (HNC) have resulted in improved long-term survival rates so there is a growing interest in long-term consequences. OBJECTIVE: The aim was to perform a smartphone-based assessment to analyse the upper airway dysfunction-related symptoms in HNC 1 year after radiotherapy (RT) during social distancing due to COVID-19. METHODS & PROCEDURES: Smartphone-based assessment on upper airway function 1 year after RT was performed. Upper airway functions include perceived impact of voice on quality of life (Voice Handicap Index, VHI-30), swallowing (Functional Oral Intake, FOIS; and Swallowing Quality of Life questionnaire, SWAL-QOL) and sleep-disordered breathing (Pittsburgh Sleep Quality Index, PSQI) assessments. Additionally, quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. OUTCOMES & RESULTS: The HNC group presented worse results in the VHI-30 scale, in the three subscales (p < 0.001). Swallowing function also presented worse results in the HNC group, with a lower score in the FOIS questionnaire (p < 0.001) and a poorer score in the SWAL-QOL (p < 0.001). Regarding to the sleep-disordered breathing, the HNC group presented poorer scores in all subscales (p < 0.05). The HNC group also presented worse scores in quality of life. CONCLUSION: Our findings showed that HNC survivors presented a poorer upper airway function and a worse quality of life. This population needs to be systematically screened for those function impairments. WHAT THIS PAPER ADDS: What is already known on the subject Head-and-neck cancer radiotherapy treatment is anatomically related to the upper airway, involved in several functions such as breathing, swallowing and speech that could be affected by the treatment. Public health restrictions caused by the COVID-19 pandemic have made it difficult, and in many cases impossible, to see patients in person and complete assessments that are often crucial to improve their approach. Telephone interviews appear to be largely equivalent to face-to-face interviews, which could solve these problems. What this paper adds to existing knowledge The aim of this study was to perform a smartphone-based assessment to analyse the upper airway dysfunction-related symptoms in head-and-neck cancer survivors 1 year after radiotherapy treatment. Our findings showed that head-and-neck cancer survivors who have been treated with radiotherapy presented a poorer upper airway function, with subjective speech and voice problems, swallowing and sleep-disordered breathing compared to a control group matched for age and sex 1 year after the treatment. What are the potential or actual clinical implications of this work? The results of this study will allow a better approach to treatment of head-and-neck cancer survivors.

Clinical and upper airway characteristics of 3715 patients with the Omicron variant of SARS-Cov-2 in Changchun, China.

OBJECTIVE: The spread of the novel SARS-Cov-2 variant Omicron created a challenging public health situation in a number of countries. In March 2022, Omicron emerged in Changchun, China, and the number of patients infected rapidly increased. The prevalence of Omicron infection symptoms differs from that of Delta, with more upper airway clinical symptoms apparent. This study aimed to investigate the clinical and upper airway characteristics of the Omicron variant. MATERIALS AND METHODS: In this retrospective study, we collected data from participants in Changchun who had tested positive for Omicron with quantitative polymerase chain reaction between 10 March and 30 May 2022 using telephone interviews. The questionnaire was designed by the research team based on the number of upper airway symptoms using the visual analogue scale. We also considered age, sex, vaccination status, general symptoms, and cure period. RESULTS: A total of 3715 patients (2056 males and 1659 females) with mild COVID-19 from the Omicron variant were included. The patients had a mean age of 38.63 ( ± 13.97) years (range 2-86 years). The vaccine uptake rate was 91.33 % (8.66 %, 4.58 %, 65.33 %, and 21.43 % had received zero, one, two, and three doses, respectively). The incidence of upper airway symptoms, including throat and nasal symptoms, was 54.21 %. Throat symptoms were the most common during Omicron infection (49.12 %). Nasal symptoms were also common (20.08 %). The incidence of lower airway symptoms was 25.60 %, and gastrointestinal symptoms was 10.87 %. The incidence of general symptoms was 55.26 %. The cure period ranged from three to 37 days, with a mean of 10.24 ± 4.69 days. We compared the upper airway symptom severity for Omicron among different vaccination statuses and found no differences. CONCLUSIONS: The main clinical characteristics of the SARS-Cov-2 Omicron variant are upper airway symptoms and general symptoms. Fever remains the most common symptom, followed by mild dry cough. There was no association between Omicron infection and COVID-19 vaccines, and the vaccination status might have been ineffective against upper airway symptom severity by Omicron.

A CASE OF TRACHEOBRONCHIAL AMYLOIDOSIS PRESENTING AS SYNCOPE

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Amyloidosis of the respiratory tract is rare. We present a case of tracheobronchial amyloid presenting as multifactorial cough with syncope. CASE PRESENTATION: The patient is a 65-year-old man with history of hypertension, hyperlipidemia, and allergic rhinitis who presented to the ED after a syncopal event. Two weeks prior, he had a new-onset myalgias and severe persistent cough, not resolving with over-the-counter medications. During a coughing paroxysm, he experienced a brief loss of consciousness. On arrival, his vital signs and physical exam were within normal limits except for Mallampati II, BM of 38.8 kg/m2. Basic laboratory testing was also unremarkable except for troponin T of 251 nl/dL and NT-ProBNP of 1181 pg/mL. NP swab for Sars-CoV-19 (PCR), Influenza A and B were not detected. CT of the chest revealed an area of circumferential mural soft tissue thickening in the left lower lobe bronchi. Cardiac MRI showed an area of subepicardial delayed enhancement, suggestive of myocardial inflammation or edema. Flexible bronchoscopy confirmed that the left lower lobe bronchus and proximal subsegmental bronchi had an infiltrative process with a friable, erythematous irregular mucosal surface. Forceps biopsy sampling and staining with Congo red, sulfate Alcian blue and Trichome stain were positive for amyloid deposits. Immunostain revealed predominantly CD3 positive T-Cells. Mass spectometry showed AL (lamda)-type amyloid deposition. GMS and AFB stains were negative. Telemetry showed 2-3 second pauses, correlated with episodes of cough. DISCUSSION: Amyloidosis is a disorder caused by misfolding of proteins and fibril accumulation in the extracellular space. It can present as a diffuse or localized process to one organ system. Several patterns of lung involvement have been described: nodular pulmonary, diffuse alveolar-septal, cystic, pleural, and tracheobronchial amyloidosis. Tracheobronchial amyloidosis is usually limited and not associated with systemic disease or hematologic malignancy. It can be asymptomatic, or can present with cough, dyspnea or signs of obstruction, including postobstructive pneumonia. Congo Red stained samples reveal green birefringence under polarized light microscopy. Further analysis of proteins usually reveals localized immunoglobulin light chains (AL). Cough syncope is due to increased intrathoracic pressure, decreased venous return and cardiac output, stimulation of baroreceptors, decreased chronotropic response, arterial hypotension and decreased cerebral perfusion. Our patient presented with multifactorial cough (possible viral infection, upper airway cough syndrome, amyloidosis) causing sinus pauses and syncope, on underlying myocarditis. CONCLUSIONS: Amyloid infiltration of the respiratory system is rare, but it should be considered in the differential diagnosis of airway disorders, nodular or cystic lung diseases, and pleural processes. Reference #1: Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev 2017;26: 170046 [https://doi.org/10.1183/16000617.0046-2017]. Reference #2: Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996 Feb 15;124(4):407-13. doi: 10.7326/0003-4819-124-4-199602150-00004 Reference #3: Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014 Feb;108(2):244-51. doi: 10.1016/j.rmed.2013.10.020. Epub 2013 Nov 5. PMID: 24238768. DISCLOSURES: No relevant relationships by Amarilys Alarcon-Calderon No relevant relationships by Ashokakumar Patel

Performance Comparison of Oral, Laryngeal and Thoracic Sounds in the Detection of COVID-19 by Employing Machine Learning Techniques

COVID-19 can directly or indirectly cause lung involvements by crossing the upper airways. It is essential to quickly detect the lung involvement condition and to follow up and treat these patients by early hospitalization. In recent COVID-19 diagnosis procedure, PCR testing is applied to the samples taken from the patients and a quarantine period is applied to the patient until the test results are received. As a complement to PCR tests and for faster diagnosis, thin-section lung computed tomography (CT) imaging is used in COVID-19 patients. In this study, it is aimed to develop a method that is as reliable as CT, and compared to CT, less risky, more accessible, and less costly for the diagnosis of COVID-19 disease. For this purpose, first speech and cough sounds from the oral, laryngeal and thoracic regions of COVID-19 patients and healthy individuals were obtained with the multi-channel voice recording system we proposed, the obtained data were processed with machine learning methods and their accuracies in COVID-19 diagnosis were presented comparatively. In our study, the best results were obtained with the features extracted from the cough sounds taken from the oral region. © 2022 IEEE.

COVID-19 Omicron variant-induced laryngitis.

OBJECTIVES: The COVID-19 omicron variant has a low affinity for the lower respiratory tract. However, upper respiratory tract symptoms, such as nasal discharge and sore throat, characterize the infection with this variant. Therefore, in laryngeal stenosis, disease severity assessment through blood oxygen saturation has not been useful. METHODS: We report the case of "omicron laryngitis" in a 59-year-old male who visited the ear, nose, and throat (ENT) clinic with complaints of a sore throat and difficulty in swallowing saliva that persisted for a day. RESULTS: Laryngoscopy revealed severe swelling of the transglottic region and exudates on the larynx. He was then diagnosed with COVID-19 and subjected to emergency tracheostomy for airway management. Until the emergence of the omicron variant, COVID-19 showed mainly lower airway and mild upper airway inflammatory features. However, upper airway stenosis should be suspected in cases presenting with "muffled speech," "dysphagia," "severe pain on swallowing," and "inspiratory dyspnea or stridor." CONCLUSION: Therefore, laryngeal and pharyngeal evaluation using a flexible laryngoscope under appropriate infection control measures is necessary, considering the possibility of progression to fatal laryngeal stenosis, as noted in this case.

Insomnia affects patient-reported outcome in sleep apnea treated with hypoglossal nerve stimulation.

Objective: Comorbid insomnia may impact outcomes of patients with obstructive sleep apnea (OSA) receiving hypoglossal nerve stimulation with respiratory sensing (HNS) therapy. To examine whether the presence of insomnia measured using the Insomnia Severity Index (ISI) is associated with patient-reported outcomes and objective OSA measures in patients receiving HNS therapy. Methods: In this retrospective chart review, patients with an HNS implant and ISI score at follow-up assessment were categorized as having moderate/severe insomnia or no/subthreshold insomnia. OSA-related data (Apnea Hypopnea Index, AHI; Oxygen Desaturation Index, ODI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and overall patient satisfaction was compared between these patient categories. Correlations between ISI scores and each of these variables were examined. Results: Of the 132 patients, 26% had moderate/severe insomnia at follow-up assessment. ESS and FOSQ scores were worse in the insomnia group at baseline, follow-up, and in the change from baseline, but AHI and ODI scores did not differ between patients with and without insomnia. Frequency of overall satisfaction at follow-up was lower in the insomnia group (58.8% vs. 92.8% with no insomnia, P < .001). Patients with insomnia were more likely to have depression (56% vs. 27% without insomnia, P < .002). Conclusions: Insomnia is associated with worse patient-reported outcomes of daytime sleepiness and sleep-related quality of life in patients with OSA receiving HNS therapy. Depression is more prevalent in patients with comorbid insomnia. The ISI may help physicians to address comorbid insomnia and achieve high patient satisfaction and adherence to HNS therapy. Level of Evidence: 4.

Quantitative evaluation of aerosol generation from upper airway suctioning assessed during tracheal intubation and extubation sequences in anaesthetized patients.

BACKGROUND: Open respiratory suctioning is defined as an aerosol generating procedure (AGP). Laryngopharyngeal suctioning, used to clear secretions during anaesthesia, is widely managed as an AGP. However, it is uncertain whether upper airway suctioning should be designated as an AGP due to the lack of both aerosol and epidemiological evidence. AIM: To assess the relative risk of aerosol generation by upper airway suctioning during tracheal intubation and extubation in anaesthetized patients. METHODS: This prospective environmental monitoring study was undertaken in an ultraclean operating theatre setting to assay aerosol concentrations during intubation and extubation sequences, including upper airway suctioning, for patients undergoing surgery (N=19). An optical particle sizer (particle size 0.3-10 µm) sampled aerosol 20 cm above the patient's mouth. Baseline recordings (background, tidal breathing and volitional coughs) were followed by intravenous induction of anaesthesia with neuromuscular blockade. Four periods of laryngopharyngeal suctioning were performed with a Yankauer sucker: pre-laryngoscopy, post-intubation, pre-extubation and post-extubation. FINDINGS: Aerosol was reliably detected {median 65 [interquartile range (IQR) 39-259] particles/L} above background [median 4.8 (IQR 1-7) particles/L, P<0.0001] when sampling in close proximity to the patient's mouth during tidal breathing. Upper airway suctioning was associated with a much lower average aerosol concentration than breathing [median 6.0 (IQR 0-12) particles/L, P=0.0007], and was indistinguishable from background (P>0.99). Peak aerosol concentrations recorded during suctioning [median 45 (IQR 30-75) particles/L] were much lower than during volitional coughs [median 1520 (IQR 600-4363) particles/L, P<0.0001] and tidal breathing [median 540 (IQR 300-1826) particles/L, P<0.0001]. CONCLUSION: Upper airway suctioning during airway management was not associated with a higher aerosol concentration compared with background, and was associated with a much lower aerosol concentration compared with breathing and coughing. Upper airway suctioning should not be designated as a high-risk AGP.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

COVID-19, anosmia, and ageusia in atopic children.

More than a year and a half after the beginning of the coronavirus disease 2019 (COVID-19) pandemic, symptoms, such as loss of smell and taste (anosmia and ageusia, respectively), remain difficult to characterize and quantify, especially in children, since no validated tests to assess these disorders are available. However, these symptoms can also be seen in children, although less frequently than observed in the adult population. In this article, we present the results of a national survey that collected the responses of 267 Italian pediatricians on the presence of anosmia and ageusia in children affected by COVID-19. These data were then compared with existing literature.

Cough in the Elderly During the COVID-19 Pandemic.

INTRODUCTION: The prevalence of chronic cough increases with age. However, data on the prevalence and background disorders of cough subtypes in the elderly are scarce. The objective of this study was to identify the point prevalence and risk factors of acute, subacute, and chronic cough in an elderly community-based population. METHODS: This was a cross-sectional email survey amongst 26,205 members of the Finnish Pensioners' Federation during the COVID-19 pandemic in spring 2021. RESULTS: The response rate was 23.6% (6189). 5983 subjects aged at least 64 years were included in the analyses (mean 72.6 years, 66.3% female). The point prevalence of daily acute, subacute, and chronic cough were 1.4%, 0.7%, and 9.6%, respectively. Only 0.4% of the subjects had a COVID-19 infection. In the multivariate analyses, chronic rhinosinusitis, and obstructive sleep apnoea were common risk factors for all cough subtypes. Chronic cough had several risk factors; Bronchiectasis (OR 5.79 (CI95% 2.70-12.41)), current asthma (2.67 (2.02-3.54)), chronic rhinosinusitis (2.51 (1.94-3.24)), somatic symptom score (1.13 per symptom (1.07-1.19)), family history of chronic cough (1.88 (1.54-2.30)), gastro-oesophageal reflux disease (1.86 (1.50-2.32)), advanced age (1.20 per decade (1.02-1.40)), chronic obstructive pulmonary disease (1.74 (0.99-3.05)), dog ownership (1.42 (1.07-1.89)), and obstructive sleep apnoea (1.41 (1.16-1.73)). CONCLUSION: Acute and subacute cough, as well as previous COVID-19 infection, were uncommon in this Finnish elderly population. The prevalence of chronic cough was higher than that previously found in younger adults. Chronic cough is a multifactorial disorder in the elderly.

The Impact of Ubiquitous Face Masks and Filtering Face Piece Application During Rest, Work and Exercise on Gas Exchange, Pulmonary Function and Physical Performance: A Systematic Review with Meta-analysis.

BACKGROUND: Protection against airborne infection is currently, due to the COVID-19-associated restrictions, ubiquitously applied during public transport use, work and leisure time. Increased carbon dioxide re-inhalation and breathing resistance may result thereof and, in turn, may negatively impact metabolism and performance. OBJECTIVES: To deduce the impact of the surgical mask and filtering face piece type 2 (FFP2) or N95 respirator application on gas exchange (pulse-derived oxygen saturation (SpO2), carbon dioxide partial pressure (PCO2), carbon dioxide exhalation (VCO2) and oxygen uptake (VO2)), pulmonary function (respiratory rate and ventilation) and physical performance (heart rate HR, peak power output Wpeak). METHODS: Systematic review with meta-analysis. Literature available in Medline/Pubmed, the Cochrane Library and the Web of Knowledge with the last search on the 6th of May 2021. Eligibility criteria: Randomised controlled parallel group or crossover trials (RCT), full-text availability, comparison of the acute effects of ≥ 1 intervention (surgical mask or FFP2/N95 application) to a control/comparator condition (i.e. no mask wearing). Participants were required to be healthy humans and > 16 years of age without conditions or illnesses influencing pulmonary function or metabolism. Risk of bias was rated using the crossover extension of the Cochrane risk of bias assessment tool II. Standardised mean differences (SMD, Hedges' g) with 95% confidence intervals (CI) were calculated, overall and for subgroups based on mask and exercise type, as pooled effect size estimators in our random-effects meta-analysis. RESULTS: Of the 1499 records retrieved, 14 RCTs (all crossover trials, high risk of bias) with 25 independent intervention arms (effect sizes per outcome) on 246 participants were included. Masks led to a decrease in SpO2 during vigorous intensity exercise (6 effect sizes; SMD = - 0.40 [95% CI: - 0.70, - 0.09], mostly attributed to FFP2/N95) and to a SpO2-increase during rest (5 effect sizes; SMD = 0.34 [95% CI: 0.04, 0.64]); no general effect of mask wearing on SpO2 occurred (21 effect sizes, SMD = 0.34 [95% CI: 0.04, 0.64]). Wearing a mask led to a general oxygen uptake decrease (5 effect sizes, SMD = - 0.44 [95% CI: - 0.75, - 0.14]), to slower respiratory rates (15 effect sizes, SMD = - 0.25 [95% CI: - 0.44, - 0.06]) and to a decreased ventilation (11 effect sizes, SMD = - 0.43 [95% CI: - 0.74, - 0.12]). Heart rate (25 effect sizes; SMD = 0.05 [95% CI: - 0.09, 0.19]), Wpeak (9 effect sizes; SMD = - 0.12 [95% CI: - 0.39, 0.15]), PCO2 (11 effect sizes; SMD = 0.07 [95% CI: - 0.14, 0.29]) and VCO2 (4 effect sizes, SMD = - 0.30 [95% CI: - 0.71, 0.10]) were not different to the control, either in total or dependent on mask type or physical activity status. CONCLUSION: The number of crossover-RCT studies was low and the designs displayed a high risk of bias. The within-mask- and -intensity-homogeneous effects on gas exchange kinetics indicated larger detrimental effects during exhausting physical activities. Pulse-derived oxygen saturation was increased during rest when a mask was applied, whereas wearing a mask during exhausting exercise led to decreased oxygen saturation. Breathing frequency and ventilation adaptations were not related to exercise intensity. FFP2/N95 and, to a lesser extent, surgical mask application negatively impacted the capacity for gas exchange and pulmonary function but not the peak physical performance. Registration: Prospero registration number: CRD42021244634.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-ß1 levels between smokers and non-smokers.

Proteomic Signature of Host Response to SARS-CoV-2 Infection in the Nasopharynx.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global health pandemic. COVID-19 severity ranges from an asymptomatic infection to a severe multiorgan disease. Although the inflammatory response has been implicated in the pathogenesis of COVID-19, the exact nature of dysregulation in signaling pathways has not yet been elucidated, underscoring the need for further molecular characterization of SARS-CoV-2 infection in humans. Here, we characterize the host response directly at the point of viral entry through analysis of nasopharyngeal swabs. Multiplexed high-resolution MS-based proteomic analysis of confirmed COVID-19 cases and negative controls identified 7582 proteins and revealed significant upregulation of interferon-mediated antiviral signaling in addition to multiple other proteins that are not encoded by interferon-stimulated genes or well characterized during viral infections. Downregulation of several proteasomal subunits, E3 ubiquitin ligases, and components of protein synthesis machinery was significant upon SARS-CoV-2 infection. Targeted proteomics to measure abundance levels of MX1, ISG15, STAT1, RIG-I, and CXCL10 detected proteomic signatures of interferon-mediated antiviral signaling that differentiated COVID-19-positive from COVID-19-negative cases. Phosphoproteomic analysis revealed increased phosphorylation of several proteins with known antiviral properties as well as several proteins involved in ciliary function (CEP131 and CFAP57) that have not previously been implicated in the context of coronavirus infections. In addition, decreased phosphorylation levels of AKT and PKC, which have been shown to play varying roles in different viral infections, were observed in infected individuals relative to controls. These data provide novel insights that add depth to our understanding of SARS-CoV-2 infection in the upper airway and establish a proteomic signature for this viral infection.

Daytime polysomnography to perform titration for upper airway stimulation in patients with obstructive sleep apnea.

PURPOSE: Upper airway stimulation (UAS) is an innovative treatment for patients with obstructive sleep apnea (OSA). UAS titrations are performed 3 months after activation of the device to optimize its effectiveness. In general, these titrations are performed during an in-laboratory overnight polysomnography (PSG). However, overnight titrations are expensive and can be logistically challenging because they are labor-intensive which causes shortage of sleep technicians available for night shifts. In addition, recently, overnight PSGs were postponed and canceled due to the COVID-19 pandemic. We aimed to assess the feasibility of a daytime PSG to perform titration of UAS therapy as an alternative for a conventional overnight PSG. METHODS: We performed a prospective single-center observational cohort study. Patients were included when planned for UAS titration; this was approximately 6 months after UAS activation. Data on sleep architecture, patient experience, and respiratory outcomes were collected to evaluate the feasibility. An overnight follow-up PSG 12 months after implantation was used to compare sleep architecture and therapy response. RESULTS: Of 23 patients, four were excluded from analysis because of technical issues during PSG. Even though patients slept significantly shorter during the daytime PSG, this was enough time to complete the titration successfully with 30-min sleep in final therapeutic settings in 84% of the patients. Patients (94%) had a positive experience with the daytime titration. Respiratory outcomes were significantly reduced during titration and were maintained at the 12-month follow-up. CONCLUSION: Daytime titrations are a valuable alternative for conventional overnight titrations. Our findings suggest the implementation of daytime titrations as standard of care. This will contribute to easier logistics and better work circumstances for sleep technicians without jeopardizing titration quality.