Inflammatory endotypes of CRSwNP and responses to COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly become a great public health hazard globally. Nasal epithelial cells are an important site for SARS-CoV-2 infection and replication. The purpose of this review is to summarize recent findings on the endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) and the potential impact of SARS-CoV-2 infection. RECENT FINDINGS: Endotypes of CRSwNP are characterized by type 1, type 2 and type 3 inflammation according to patterns of inflammatory cells and the cytokines expressed in nasal tissue. Nasal epithelial cells show the highest expression of angiotensin-converting enzyme 2 (ACE2), the receptor for attachment and entry of SARS-CoV-2 into host cells, among all investigated cells in the respiratory tree. SARS-CoV-2 infection likely leads to increased activation of T-helper-1 (Th1) cell responses. Recent studies further suggest that ACE2 may be upregulated by type 1 and downregulated by type 2 inflammatory cytokines in nasal epithelial cells. SUMMARY: Expression of ACE2 in nasal epithelial cells is influenced by inflammatory endotypes of CRSwNP. Type 1 inflammation in nasal tissue may increase the risk of SARS-CoV-2 infection by upregulating ACE2 expression. However, clinical association between CRSwNP and COVID-19 is still unclear.

Clinical characteristics of acute rhinosinusitis in COVID-19 a post hoc analysis of a longitudinal study.

BACKGROUND: Acute rhinosinusitis (ARS) is a common and well-defined disorder, primarily of viral aetiology, with rhinovirus and coronavirus accounting for more than 50% of viral ARS. The fight with COVID-19 pandemic resulted in an increased availability viral testing, which in turn allowed testing for presence of SARS-Cov-2 in all patients presenting common cold (or ARS) symptoms. The aim of this study was to assess the clinical characteristics of acute rhinosinusitis in patients diagnosed with COVID-19. METHODOLOGY/PRINCIPAL: This study is a post-hoc analysis. Patients symptoms were evaluated using a structured questionnaire twice: directly after a positive SARS-Cov-2 result and 7-12 days following the first evaluation. Subjects were asked about presence of nasal and systemic symptoms as well as headache. RESULTS: A total of 130 COVID-19 symptomatic patients were recruited into the study, 58 (45%) patients met EPOS2020 diagnostic criteria for ARS. Of all ARS patients, 72% presented with rhinorrhoea, 69% with pain perceived over paranasal sinuses, 62% with nasal congestion, 52% with cough, 45% with olfactory dysfunction, 38% with fever, 33% with facial pressure and in 22% pain was exacerbated by sinus palpation. CONCLUSIONS: Half of COVID-19 subjects has ARS. The course of SARS-Cov-2 ARS does not seem to differ significantly from ARS of other aetiologies. Since ARS in the course of COVID-19 seems to meet the definition of ARS proposed by EPOS 2020, we hypothesize that substances validated for ARS treatment, such as intranasal corticosteroids could be effective in SARS-Cov-2 ARS.

Acute unilateral isolated ptosis as a complication of sinusitis in a post-COVID-19 patient.

A fit and well young man presented to our emergency department in the UK. On examination, he had an isolated left-sided ptosis; he had a 3-day history of frontal headache which was worse on head movement. He lacked any clinical signs of cranial, orbital, or preseptal infection, and his eye movements were normal. Ten days before presentation, he tested positive for SARS-CoV-2. Inflammatory markers were moderately raised, and CT of the head did not reveal any vascular abnormality or intracranial lesion. Imaging revealed opacification, predominantly in the left facial sinuses, keeping with sinusitis. He was discharged the same evening with oral antibiotics and made a full recovery over the next few days. He remained well at 6-month follow-up. The authors convey their findings to raise awareness of a rare complication of sinusitis and to demonstrate the utility of CT imaging for diagnosing sinusitis and ruling out severe pathology.

A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012-2022.

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

Has COVID-19 Changed Pediatric Acute Rhinosinusitis Epidemiology During the First 2 Pandemic Years?

OBJECTIVE: To study national pediatric acute rhinosinusitis (ARS) burden fluctuations before and during the first 2 coronavirus-19 (COVID) years, characterized by alternating lockdown and relaxation periods, the introduction of COVID vaccines, and the emergence of nonalpha COVID variants. METHODS: This was a cross-sectional, population-based study covering the 3 pre-COVID years and the first 2 COVID years from a big database of the largest Israeli Health Maintenance Organization. For comparison purposes, we explored ARS burden trends with those of urinary tract infection (UTI), which is unrelated to viral diseases. We identified children <15 years presenting with ARS and UTI episodes and categorized them according to their age and presentation date. The average ARS and UTI episodes of the 3 pre-COVID years were used to calculate the incidence rate ratios (IRRs) of the 2 COVID years, analyzed separately. Seasonal variations were explored. RESULTS: We identified 44,483 ARS and 121,263 UTI episodes. There was a substantial reduction in ARS episodes during the COVID years (IRR 0.36, 95% CI: 0.24-0.56, P < 0.001). Although UTI episode rates also decreased during COVID (IRR 0.79, 95% CI: 0.72-0.86, P < 0.001), the reduction in ARS burden was 3-fold higher. The dominant pediatric ARS age group was between 5 and 15 years. The largest decrease in ARS burden was during the first COVID year. ARS episode distribution showed a seasonal fluctuation, with a peak during the summer months during the COVID years. CONCLUSIONS: Pediatric ARS burden decreased during the first 2 COVID years. Episode distribution was noted to be year-round.

Mucormycosis as Post Coronavirus Disease Complication.

Mucormycosis is called as black fungus, which is caused by fungus belonged to Mucorales. If this fungus, effects healthy individuals it won't cause any serious complications, but it may cause life-threatening issues when Mucorales affects individuals who have low immunity. The mortality rate of black fungus is more than 50%, and it may also range till 100% if the individual is having any preexisting or chronic disease. This was the case of a 55-year-old male patient complaint of having generalized pain in the maxillary teeth bilaterally and suffering fullness in the maxillary sinus. To check on other possible diseases, doctors have conducted other diagnosis tests, and orthopantomogram revealed in the diagnosis that there was the presence of haziness in the left maxillary sinus, which looked like an incompletely formed soap bubble and additionally he diagnosed with coronavirus disease positive. Then, doctors suggested a chest computerized tomography (CT) along with head CT excluding the brain and further investigation of this case was given below in detail. The report reveals acute necrotizing suppurative sinusitis with dead bony tissue, soft-tissue necrosis with fungal infestation showing broad hyphae with right-angle branching suggestive of mucormycosis.

Invasive Fungal Sinusitis in Post-COVID-19 Patients with Diabetes Mellitus.

OBJECTIVE: Invasive fungal sinusitis is an invasive disease associated with high mortality of up to 60%. There is a well-documented increase in rhino-orbital-cerebral fungal co-infection in COVID-19 patients. Our study aimed to determine the factors that lead to the development, the natural history of progression and the therapeutic interventions done for this grave complication. METHODS: Patients admitted in general medicine ward in King Edward Memorial (KEM) Hospital, Mumbai were included. Patient's history and examination findings were noted. Advised Investigations- imaging studies like CT scan, MRI done were noted down. Operative procedures like functional endoscopic sinus surgery (FESS), abscess drainage, dental extraction, were performed at the hospital and details were taken. Fungal cultures, sugar monitoring, liver function test, renal function test, complete blood counts, ECGs, chest X-rays, and amphotericin charting were also done.. RESULTS: On retrospective analysis of the presenting patient's records, we found that all patients had received steroids for COVID-19 treatment and had co-morbidities, especially diabetes mellitus. Prolonged hospitalization further exposes the patient to various multi-resistant bacteria making them prone to various secondary infections. CONCLUSIONS: It is of paramount importance that physicians know the associated risk factors, mentioned in our study, that may lead to invasive fungal co-infection in COVID-19 patients, and to regularly examine the patient for any developing signs so appropriate diagnosis and treatment can be initiated as early as possible. It is an unrelenting disease process that requires the utmost care, and our case series provides an in depth look of four such cases for future reference.

Is low dose of liposomal amphotericin B effective in management of acute invasive fungal rhinosinusitis? Our conclusions from Al-Mowassat University Hospital, Syria: a prospective observational study.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is a fatal infection associated with high morbidity and mortality. Although it is a rare disease, upsurge of AIFRS was noticed during the second wave of COVID-19 disease. Early diagnosis and management is the cornerstone for good outcomes. However, management of AIFRS is challengeable especially in developing countries due to limited resources and high prices of antifungal agents. No previous studies have been conducted to evaluate the outcomes of management of AIFRS in Syria. The purpose of this study is to report the results of management of AIFRS with low doses of liposomal amphotericin B in our tertiary hospital in Syria. METHODS: The outcomes of management of AIFRS cases were followed through a prospective observational study between January 2021 and July 2022. The required medical data were collected for each individual. Three-month mortality rate was studied. SPSS v.26 was used to perform the statistical analysis. Pearson Chi-square test was used to study the associations between different variables and mortality. Survival curves were plotted by the Kaplan-Meier to compare the survival probability. Log Rank (Mantel-Cox) test and Cox regression were conducted to evaluate the factors affecting survival within the follow up period. RESULTS: Of 70 cases, 36 (51.4%) were males and 34 (48.6%) were females. The mean age of patients was 52.5 years old. The most common underlying risk factor was diabetes mellitus (84.3%). The used dose of liposomal amphotericin B ranged between 2-3 mg/kg per day. The overall 3-month mortality rate was 35.7%. Significant association was found between survival and the following variables: Age, orbital involvement, stage, and comorbidity. CONCLUSION: The overall mortality rate was close to other studies. However, survival rate was worse than comparable studies in selected cases of AIFRS (older ages, involved orbits, advanced stages, and chronic immunodeficiency). Therefore, low doses of liposomal amphotericin B could be less effective in such cases and high doses are recommended.

Changes in Otorhinolaryngologic Disease Incidences before and during the COVID-19 Pandemic in Korea.

This study aimed to investigate the change in the incidence and variance of otorhinolaryngologic diseases during the coronavirus disease 19 (COVID-19) pandemic. The entire Korean population (~50 million) was evaluated for the monthly incidence of 11 common otorhinolaryngologic diseases of upper respiratory infection (URI), influenza, acute tonsillitis, peritonsillar abscess, retropharyngeal and parapharyngeal abscess, acute laryngitis and bronchitis, stomatitis and related lesions, acute sinusitis, rhinitis, otitis media, and dizziness from January 2018 through March 2021 using the International Classification of Disease (ICD)-10 codes with the data of the Korea National Health Insurance Service. The differences in the mean incidence of 11 common otorhinolaryngologic diseases before and during COVID-19 were compared using the Mann-Whitney U test. The differences in the variance of incidence before and during COVID-19 were compared using Levene's test. The incidence of all 11 otorhinolaryngologic diseases was lower during COVID-19 than before COVID-19 (all p < 0.05). The variations in disease incidence by season were lower during COVID-19 than before COVID-19 for infectious diseases, including URI, influenza, acute tonsillitis, peritonsillar abscess, retropharyngeal and parapharyngeal abscess, acute laryngitis and bronchitis, acute sinusitis, and otitis media (all p < 0.05), while it was not in noninfectious diseases, including stomatitis, rhinitis, and dizziness. As expected, the incidences of all otorhinolalryngolgic diseases were decreased. Additionally, we found that seasonal variations in infectious diseases disappeared during the COVID-19 pandemic, while noninfectious diseases did not.

An epidural brain abscess and thrombus in the superior sagittal sinus in a 12 year-old with sinusitis.

BACKGROUND: Upper respiratory infections can be complicated by acute bacterial sinusitis in pediatric patients, and usually resolve with antibiotic therapy (DeMuri and Wald, 2011). However, intracranial complications such as: epidural abscess, meningitis and more rarely cerebral sinus venous thrombosis (CSVT) can occur (Germiller et al., 2006). We report an unusual case of sinusitis complicated by an epidural abscess and later a CSVT in a young previously healthy patient. CASE DESCRIPTION: A 12-year-old female presented to the emergency department with a 9-day history of headaches and a 3-day history of fevers, rigors, nasal congestion and nonproductive cough. She later tested positive for Covid-19. CT and MRI showed extensive paranasal sinus disease and a right frontal epidural collection. MRV showed no sinovenous thrombosis. Washout and burr hole drainage alongside endoscopic sinus surgery was completed and post-op imaging showed evacuation of the epidural abscess with a small residual collection. Six days after the procedure, she experienced worsening headaches and MRV showed a nonocclusive thrombus in the superior sagittal sinus, which was treated with anticoagulation therapy. Upon follow-up, the patient showed improvement of the sinusitis, abscess and thrombus. CONCLUSION: This specific case encourages clinicians to be aware of complications, though rare, and to diagnose and treat sinusitis cases quickly. It is also important to be aware of any risk factors for thrombus formation, including an inflammatory and hypercoagulable state. In the patient's case, it was perceived that the CSVT was provoked due to the patient's Covid-19 infection, abscess, and sinus disease.

Clinical and Imaging Evaluation of COVID-19-Related Olfactory Dysfunction.

BACKGROUND: Olfactory dysfunction has been reported in 47.85% of COVID patients. It can be broadly categorized into conductive or sensorineural olfactory loss. Conductive loss occurs due to impaired nasal air flow, while sensorineural loss implies dysfunction of the olfactory epithelium or central olfactory pathways. OBJECTIVES: The aim of this study was to analyze the clinical and imaging findings in patients with COVID-related olfactory dysfunction. Additionally, the study aimed to investigate the possible mechanisms of COVID-related olfactory dysfunction. METHODS: The study included 110 patients with post-COVID-19 olfactory dysfunction, and a control group of 50 COVID-negative subjects with normal olfactory function. Endoscopic nasal examination was performed for all participants with special focus on the olfactory cleft. Smell testing was performed for all participants by using a smell diskettes test. Olfactory pathway magnetic resonance imaging (MRI) was done to assess the condition of the olfactory cleft and the dimensions and volume of the olfactory bulb. RESULTS: Olfactory dysfunction was not associated with nasal symptoms in 51.8% of patients. MRI showed significantly increased olfactory bulb dimensions and volume competed to controls. Additionally, it revealed olfactory cleft edema in 57.3% of patients. On the other hand, radiological evidence of sinusitis was detected in only 15.5% of patients. CONCLUSION: The average olfactory bulb volumes were significantly higher in the patients' group compared to the control group, indicating significant edema and swelling in the olfactory bulb in patients with COVID-related olfactory dysfunction. Furthermore, in most patients, no sinonasal symptoms such as nasal congestion or rhinorrhea were reported, and similarly, no radiological evidence of sinusitis was detected. Consequently, the most probable mechanism of COVID-related olfactory dysfunction is sensorineural loss through virus spread and damage to the olfactory epithelium and pathways.

Split-bolus, single-phase contrast enhanced CT: a one-stop shop for invasive fungal sinusitis.

Contrast-enhanced magnetic resonance imaging is considered the imaging modality of choice for invasive fungal sinusitis (IFS); however, it is not feasible to perform emergency CEMRI especially in the setting of COVID-19. The CECT protocol for evaluation of suspected IFS can be modified by using split-bolus, single-phase CT as it provides an optimal soft tissue demonstration of sinonasal disease; extrasinus spread to orbit, and intracranial involvement along with simultaneous opacification of the internal carotid artery and cavernous sinus. The extent of bone erosion can also be well delineated on the multiplanar reconstructions (MPRs) in the bone window. Further a structured reporting format can help provide optimal surgical guidance in cases of IFS.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

Treatment of infection and inflammation associated with COVID-19, multi-drug resistant pneumonia and fungal sinusitis by nebulizing a nanosilver solution.

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.

Invasive Mucormycosis and Aspergillosis Coinfection Associated with Post-COVID-19 Pneumonia in a Tertiary Care Hospital.

Acute invasive fungal rhinosinusitis is a rare infection primarily affecting patients with co-morbidities like immunosuppression and poorly controlled diabetes. Mucormycosis is increasingly being reported in patients with SARS-CoV-2 (COVID-19). However, reports of coinfection of aspergillosis and mucormycosis involving nose, paranasal sinuses, orbit, and brain are rare in literature. We aimed to evaluate the patient demographics, clinical presentation, and management of cases presenting with mixed infection. We carried out retrospective analysis of 12 patients with confirmed diagnosis of mixed invasive fungal infections post-COVID-19 disease out of 70 cases of COVID-19-associated mucormycosis (CAM) presenting to a tertiary-level hospital in North India from May to June 2021. All patients had diabetes mellitus; the mean age was 48 years. The common presenting features were headache, nasal congestion, palatal ulcer, and vision loss accompanied by facial pain and swelling. Two patients developed cerebral abscess during the course of treatment; three patients had concurrent COVID-19 pneumonia. All patients received systemic liposomal amphotericin B and serial surgical debridements. The overall mortality rate was 16.7%. Our study demonstrates that mucormycosis and aspergillosis are angioinvasive mycoses that are clinically and radiologically identical. KOH direct mount of clinical sample showing septate hyphae should be extensively searched for aseptate hyphae after digestion and clearing of the tissue. A high index of suspicion of mixed infection post-COVID-19 and early initiation of liposomal amphotericin B followed by prompt surgical intervention can reduce the overall morbidity and mortality among patients with this condition.

Invasive Fungal Sinusitis in Post-COVID-19 Patients with Diabetes Mellitus.

OBJECTIVE: Invasive fungal sinusitis is an invasive disease associated with high mortality of up to 60%. There is a well-documented increase in rhino-orbital-cerebral fungal co-infection in COVID-19 patients. Our study aimed to determine the factors that lead to the development, the natural history of progression and the therapeutic interventions done for this grave complication. METHODS: Patients admitted in general medicine ward in King Edward Memorial (KEM) Hospital, Mumbai were included. Patient's history and examination findings were noted. Advised Investigations- imaging studies like CT scan, MRI done were noted down. Operative procedures like functional endoscopic sinus surgery (FESS), abscess drainage, dental extraction, were performed at the hospital and details were taken. Fungal cultures, sugar monitoring, liver function test, renal function test, complete blood counts, ECGs, chest X-rays, and amphotericin charting were also done.. RESULTS: On retrospective analysis of the presenting patient's records, we found that all patients had received steroids for COVID-19 treatment and had co-morbidities, especially diabetes mellitus. Prolonged hospitalization further exposes the patient to various multi-resistant bacteria making them prone to various secondary infections. CONCLUSIONS: It is of paramount importance that physicians know the associated risk factors, mentioned in our study, that may lead to invasive fungal co-infection in COVID-19 patients, and to regularly examine the patient for any developing signs so appropriate diagnosis and treatment can be initiated as early as possible. It is an unrelenting disease process that requires the utmost care, and our case series provides an in depth look of four such cases for future reference.

Pharmacokinetic Evidence of Steady and Sustained Drug Release from Long-Acting Implantable Corticosteroid Matrices for Chronic Rhinosinusitis.

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.