Impact of COVID-19 Lockdown on Stress and Antireflux Diet Adherence of Patients with Laryngopharyngeal Reflux: Our Experience on 32 patients.

Olfactory dysfunction was one of the most common symptom of infection with the Wuhan strain of SARS-CoV-2 and could persist for several months after symptom onset. The pathogenesis of prolonged olfactory dysfunction (OD) remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed COVID-19 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD.

Objective: To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). Data sources: PubMed, Cochrane Library, and Scopus. Review methods: Three investigators search database for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. Authors performed a bias analysis of papers and provided recommendations for future studies. Results: A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The numbers of hypo- and nasopharyngeal acid reflux events were significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one report did not find group differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was an important heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the draw of clear conclusion. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls. Conclusion: Laryngopharyngeal reflux and GERD may be a contributing factors of CRS therapeutic resistance, but future studies are still needed to confirm the association considering nonacid reflux event.

LETTER TO EDITOR

Objective: To study the profile of patients with obstructive sleep apnea syndrome (OSAS) and laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) and to compare their reflux findings with LPR patients without OSAS. Design: Prospective controlled study. Methods: Patients with LPR and OSAS were prospectively recruited from Augustus 2019 to June 2020. The profile of hypopharyngeal reflux events (HRE) of patients was studied through a breakdown of the HEMII-pH findings over the 24-hour of testing. Reflux symptom score (RSS), gastrointestinal and HEMII-pH outcomes were compared between LPR patients and patients with LPR and OSAS. Multivariate analysis was used to study the relationship between reflux data and the following sleep outcomes: Apnea-Hypopnea Index, Epworth Slippiness Scale (ESS) and paradoxical sleep data. Results: A total of 89 patients completed the study. There were 45 patients with LPR and 44 subjects with both OSAS and LPR. The numbers of upright and daytime HREs and the otolaryngological RSS were significantly higher in patients with LPR compared with those with OSAS and LPR. There was a significant positive association between RSS quality of life score and ESS (p=0.001). The occurrence of HREs in the evening was associated with higher ESS (p=0.015). Patients with OSAS, LPR and GERD had higher number of nocturnal HREs compared with those without GERD (p=0.001). Conclusion: The presence of OSAS in LPR patients is associated with less severe HEMII-pH and ear, nose and throat symptoms. There may have different OSAS patient profiles according to the occurrence of GERD.

Dear Editor,We reviewed the article entitled: “Analysis of reflux as the etiology of laryngeal dysplasia progression through a matched case-control study ”.1 The authors did not find differences in the level of pepsin, enterokinase and bilirubin in laryngeal dysplasia (LD) of patients with malignant transformationversus those without transformation. The involvement of reflux in the development of LD and laryngeal cancers is an important topic and the realization of such a study is important. However, we wish to draw attention to many points.First, it is difficult to know if the included patients with tissue pepsin really suffered from reflux. The detection of pepsin into the tissue means that patients had some pharyngeal reflux events the day before the surgery but cannot confirm the diagnosis. The sensitivity of pepsin detection in laryngeal tissue depends on the technique and the material (antibodies), reaching 75 to 85% depending on the type of reflux (acid versus nonacid).2 Moreover, we have no detailed information about the immunostaining technique, limiting the reproducibility of the protocol. The presence of pepsin into the tissue does not ensure the reflux diagnosis. Thus, for example, it has been showed that the back flow of gastric content and the deposit of pepsin into the tissue are influenced by the meals preceding the sample collection, making the pepsin tissue a poorly reliable marker of reflux.3 To improve the sensitivity, authors1 could have performed hypopharyngeal-esophageal pH-impedance monitoring, which is the only way to confirm the diagnosis.4Second, the LD malignant transformation involves many factors such as tobacco history, environmental factors, genetic, or immune response.5 The authors did not provide information about the tobacco history (pack-year data) of groups, which is an important data to consider the risk of malignant transformation. Even many years after the tobacco cessation, it is conceivable that patients with long/more severe history of tobacco consumption may have more cell mucosa DNA impairments and a higher risk to develop cancer.Third, the focus on pepsin as the only enzyme associated with malignant transformation limits the understanding of transformation mechanisms. More than 50% of patients had mixed or nonacid reflux,4 in which the activity of pepsin is decreased regarding the alkaline pH of refluxate. To reliably investigate the involvement of reflux in the malignant transformation, authors have to consider the entire content of refluxate, including bile salts and trypsin.4 Furthermore, bile salts may be involved in laryngopharyngeal malignant transformation.6In future studies, reflux has to be diagnosed at the LD diagnosis time and physicians have to follow the reflux clinical course over the time. More than 50% of reflux patients had chronic course,4which leads to a potential higher risk to develop cell DNA damage and lesions. Thus, cross-sectional study design is probably not adequate to study a disease association involving chronic and repeated exposure.Acknowledgments: No.

Objective: To investigate prevalence and epidemiological and clinical factors associated with OD and GD in COVID-19 patients according to the disease severity. Study design: Cross-sectional study. Methods: A total of 2,579 patients with a positive diagnosis of COVID-19 were identified between March 22 and June 3, 2020 from 18 European hospitals. Epidemiological and clinical data were extracted. Otolaryngological symptoms, including OD and GD were collected through patient-reported outcome questionnaire and sniffin-sticks tests were carried out in a subset of patients. Results: A total of 2,579 patients were included, including 2,166 mild (84.0%), 144 moderate (5.6%) and 269 severe-to-critical (10.4%) patients. Mild patients presented an otolaryngological picture of the disease with OD, GD, nasal obstruction, rhinorrhea and sore throat as the most prevalent symptoms. The prevalence of subjective OD, GD were 73.7 and 46.8% and decrease with the severity of the disease. Females had higher prevalence of subjective OD and GD compared with males. Diabetes was associated with a higher risk to develop GD. Among the subset of patients who benefited from psychophysical olfactory evaluations, there were 75 anosmic, 43 hyposmic and 113 normosmic patients. The prevalence of anosmia significantly decreased with the severity of the disease. Anosmia or hyposmia were not associated with any nasal disorder, according to SNOT-22. Conclusion: OD and GD are more prevalent in patients with mild COVID-19 compared with individuals with moderate, severe or critical diseases. Females might have a higher risk of developing OD and GD compared with males.

pH-study is a routine procedure in some European laryngology offices to diagnose laryngopharyngeal reflux (LPR). Probe movements may complicate the testing leading to digestive symptoms and nose pains during the removal of the probe.

Objective Olfactory Findings in Hospitalized Severe COVID-19 Patients.Jerome R. Lechien, MD, PhD, MS1-4, Morgane Ducarme, MD5, Sammy Place, MD6, Carlos M. Chiesa-Estomba, MD, MS1,7, Mohamad Khalife, MD1,8, Giacomo De Riu, MD9, Luigi Angelo Vaira, MD9, Christophe de Terwangne, MD10, Shahram Machayekhi, MD10, Arnaud Marchant, MD, PhD11, Fabrice Journe, PhD2*, Sven Saussez, MD, PhD1,2,4*