Publications by authors named "Do-Yeon Cho"

86 Publications

The management of cystic fibrosis chronic rhinosinusitis: An evidenced-based review with recommendations.

Int Forum Allergy Rhinol 2021 Dec 21. Epub 2021 Dec 21.

Department of Otolaryngology-Head and Neck Surgery, Columbia University Irving Medical Center, New York, NY.

Background: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS.

Methods: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence.

Results: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS).

Conclusion: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.
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http://dx.doi.org/10.1002/alr.22953DOI Listing
December 2021

Chronic Obstructive Pulmonary Disease Is Not Associated with a Poor Prognosis in COVID-19.

Tuberc Respir Dis (Seoul) 2022 Jan 15;85(1):74-79. Epub 2021 Nov 15.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, Republic of Korea.

Background: The effect of underlying chronic obstructive pulmonary disease (COPD) on coronavirus disease 2019 (COVID-19) during a pandemic is controversial. The purpose of this study was to examine the prognosis of COVID-19 according to the underlying COPD.

Methods: COVID-19 patients were assessed using nationwide health insurance data. Comorbidities were evaluated using the modified Charlson Comorbidity Index (mCCI) which excluded COPD from conventional CCI scores. Baseline characteristics were assessed. Univariable and multiple logistic and linear regression analyses were performed to determine effects of variables on clinical outcomes. Ages, sex, mCCI, socioeconomic status, and underlying COPD were selected as variables.

Results: COPD patients showed older age (71.3±11.6 years vs. 47.7±19.1 years, p<0.001), higher mCCI (2.6±1.9 vs. 0.8±1.3, p<0.001), and higher mortality (22.9% vs. 3.2%, p<0.001) than non-COPD patients. The intensive care unit admission rate and hospital length of stay were not significantly different between the two groups. All variables were associated with mortality in univariate analysis. However, underlying COPD was not associated with mortality unlike other variables in the adjusted analysis. Older age (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.11-1.14; p<0.001), male sex (OR, 2.29; 95% CI, 1.67-3.12; p<0.001), higher mCCI (OR, 1.30; 95% CI, 1.20-1.41; p<0.001), and medical aid insurance (OR, 1.55; 95% CI, 1.03-2.32; p=0.035) were associated with mortality.

Conclusion: Underlying COPD is not associated with a poor prognosis of COVID-19.
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http://dx.doi.org/10.4046/trd.2021.0121DOI Listing
January 2022

Ivacaftor restores delayed mucociliary transport caused by Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator dysfunction in rabbit nasal epithelia.

Int Forum Allergy Rhinol 2021 Oct 26. Epub 2021 Oct 26.

Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL.

Background: Abnormal chloride (Cl ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.

Methods: Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4 hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (μOCT) after PAO1 and/or ivacaftor incubation.

Results: Ivacaftor resulted in a significant mean NPD polarization of 21.8 ± 2.1 mV, which was significantly greater than that seen in the low Cl control (12.9 ± 1.3; p = 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured by forskolin-stimulated short-circuit current (I ) (control, 37.0 ± 1.1 μA/cm ; PAO1, 24.4 ± 1.1 μA/cm ; p < 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by μOCT.

Conclusion: In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned.
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http://dx.doi.org/10.1002/alr.22907DOI Listing
October 2021

Unilateral Intervention in the Sinuses of Rabbits Induces Bilateral Inflammatory and Microbial Changes.

Front Cell Infect Microbiol 2021 14;11:585625. Epub 2021 Sep 14.

Department of Surgery, School of Medicine, University of Auckland, Auckland, New Zealand.

Background: Chronic rhinosinusitis (CRS) is a globally prevalent inflammatory condition of the paranasal sinuses which severely impairs patients' quality of life. An animal model of unilateral sinusitis by transient sinus occlusion has been described previously in rabbits. The aim of this study was to characterise the sinusitis rabbit model by investigating temporal and bilateral changes in the bacterial community and mucosal inflammation.

Methods: Development of sinusitis was achieved by endoscopically placing Merocel , a sterile nasal packing material, in the left middle meatus of six New Zealand white rabbits for four weeks. After a total period of 14 weeks, rabbits were assessed for sinusitis by endoscopic examination, magnetic resonance imaging (MRI) and histology. Swabs from the left and right middle meatus were obtained for bacterial community analysis at three time points (week 0, week 4, week 14) during the study.

Results: Endoscopic evaluation showed unilateral inflammation in all animals examined after the 4-week blocking period and at week 14. Notably, inflammatory changes were also seen in the contralateral sinus of all animals at week 4. MRI images demonstrated unilateral sinus opacification at week 4 in two rabbits, and partial unilateral sinus opacification at week 14 in one rabbit only. Histological analyses revealed substantial spatial heterogeneity of mucosal inflammation with inconsistent findings across all animals. No significant differences in mucosal inflammatory markers (such as goblet cell hyperplasia, epithelial denudation and oedema) could be identified between nostrils at week 14. The bacterial community in the rabbit sinuses was heavily dominated by at week 0 (baseline). At the end of the blocking period (week 4), bacterial alpha and beta diversity were significantly increased in both nostrils. The bacterial community composition at week 14 had primarily returned to baseline, reflecting the endoscopic and radiological results.

Conclusion: This study reaffirmed the ability for development of sinusitis without inoculation of any pathogens in a rabbit model. We were able to demonstrate bilateral sinonasal mucosal inflammation, by inducing unilateral sinus blockage, which resulted in significant changes to the sinonasal bacterial community. These findings may explain some of the clinical observations seen in CRS and warrant further research to reveal potential implications for its therapeutic management.
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http://dx.doi.org/10.3389/fcimb.2021.585625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477012PMC
October 2021

In vitro evaluation of a novel oxygen-generating biomaterial for chronic rhinosinusitis therapy.

Int Forum Allergy Rhinol 2021 Aug 26. Epub 2021 Aug 26.

Department of Otolaryngology-Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study was to develop and characterize an oxygen-generating biomaterial (OGB) as an innovative treatment strategy for CRS.

Methods: An OGB was fabricated by coating hydrophobic beeswax (BW, 15mg or 30mg) on the surface of calcium peroxide - catalase complex (CPO-CA, 30mg) and characterized using scanning electron microscopy (SEM). In vitro releases of both oxygen and hydrogen peroxide (H O ) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers.

Results: Three groups of OGBs: (1) CPO only; (2) CPO coated with CA and BW (1:1 ratio, CPO-CA(1)-BW(1)); and (3) CPO coated with CA and BW (1:0.5 ratio, CPO-CA(1)-BW(0.5) were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO-CA(1)-BW(1) = 0.11 ± 0.003, followed by CPO-CA(1)-BW(0.5) = 0.08 ± 0.010, and CPO = 0.05 ± 0.004 (p < 0.0001). H O production (mM) was significantly higher in CPO (1.87 ± 0.50) compared to CPO-CA (1)-BW(1) (0.00 ± 0.00) (p < 0.001) after 24 h. CPO-CA(1)-BW(1) showed significantly reduced cytotoxicity and increased Cl transport compared to the CPO group.

Conclusion: A novel OGB (CPO-CA-BW complex) exhibited sustained oxygen release over 7 days without significant cytotoxicity after 24 h in vitro. Preclinical studies evaluating the efficacy of OGB in CRS are warranted, especially for potential therapy in an obstruction-based CRS model.
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http://dx.doi.org/10.1002/alr.22875DOI Listing
August 2021

Above and Beyond: Periorbital Suspension for Endoscopic Access to Difficult Frontal Sinus Pathology.

Laryngoscope 2021 Aug 2. Epub 2021 Aug 2.

Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.

Objectives/hypothesis: The periorbital suspension (PS) is an advanced adjunctive technique performed during endoscopic approaches to frontal sinus pathology that would be too far lateral or superior to address using traditional endoscopic transnasal approaches. The objectives of this study are to characterize the utility of this technique for frontal sinus pathology, determine anatomic limitations, and assess clinical outcomes following surgical treatment.

Study Design: Prospective case series.

Methods: Patient data including demographics, etiology, technique, complications, and clinical follow-up were collected. Preoperative computed tomography scans were reviewed for maximum lateral and superior extent of pathology, supraorbital recess height, anterio-posterior (AP) diameter of the frontal sinus, interorbital distance, and orbital-first olfactory neuron distance.

Results: The PS approach was used in 30 surgeries (29 patients) for cerebrospinal fluid leaks (n = 5), benign tumors (n = 17), malignant tumors (n = 5), allergic fungal sinusitis (n = 2), and mucocele (n = 1) between 2018 and 2020. Approaches included 15 Draf IIB and 15 Draf III frontal sinusotomies. All pathology was surgically accessible using the PS approach and there were no intraoperative or postoperative complications. Postoperative follow-up was 11.7 ± 7.6 months. Mean recorded measurements (in mm) were as follows: maximum lateral extent -15.0 ± 7.7, superior extent 21.2 ± 7.7 in surgical plane and 20.9 ± 9.8 in the vertical plane, supraorbital recess height -2.6 ± 1.9, AP frontal sinus diameter -13.2 ± 4.7, interorbital distance -29.8 ± 5.4, and orbital-olfactory neuron distance -14.8 ± 2.9.

Conclusions: The PS technique can be safely and successfully utilized to provide endoscopic endonasal access to lateral and superior frontal sinus pathology.

Level Of Evidence: 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29797DOI Listing
August 2021

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Respirology 2021 08 26;26(8):812-815. Epub 2021 Jun 26.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.
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http://dx.doi.org/10.1111/resp.14108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447022PMC
August 2021

The impact of expanding health insurance coverage for anti-cancer drugs on cancer survival in Korea.

Cancer Med 2021 07 18;10(13):4555-4563. Epub 2021 Jun 18.

Department of Research, Health Insurance Review & Assessment Service, Wonju, South Korea.

Background: To reduce out-of-pocket costs, the Korean government expanded health insurance reimbursement in anti-cancer drugs for cancer patients in 2013. Our objective was to examine the impact of the benefit coverage expansion policy on healthcare utilization and overall survival (OS) among patients with six types of solid cancer after the policy of expanding health insurance coverage.

Methods: This study analyzed a before-and-after retrospective cohort of patients newly diagnosed with six types of solid cancer (stomach cancer, colorectal cancer, lung cancer, liver cancer, breast cancer, and prostate cancer) from January 1, 2009 to December 31, 2015 in Korea. The intervention was the expansion of reimbursement in 2013. Multivariate Cox proportional hazards regression was used to estimate the policy effect.

Results: In total, 142,579 before and 147,760 patients after the benefit expansion, and after matched by age, gender, and stage, 132,440 before and 132,440 patients after policy were included in the analysis. Almost total medical expenditure increased for five types of cancer increased. The expansion of health insurance reimbursement was associated with significantly lower overall mortality compared with pre-policy mortality for all six cancer sites.

Conclusion: The policy of expanding health insurance reimbursement might have been associated with a significant increase in survival among cancer patients by ensuring access to health care and medicine. Although the reimbursement expansion timing differs for each cancer, it is believed that eliminating delayed treatment might rather lead to reduce medical expenses and improve health outcomes.
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http://dx.doi.org/10.1002/cam4.3979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267115PMC
July 2021

LPS decreases CFTR open probability and mucociliary transport through generation of reactive oxygen species.

Redox Biol 2021 07 30;43:101998. Epub 2021 Apr 30.

Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Lipopolysaccharide (LPS) serves as the interface between gram-negative bacteria (GNB) and the innate immune response in respiratory epithelial cells (REC). Herein, we describe a novel biological role of LPS that permits GNB to persist in the respiratory tract through inducing CFTR and mucociliary dysfunction. LPS reduced cystic fibrosis transmembrane conductance regulater (CFTR)-mediated short-circuit current in mammalian REC in Ussing chambers and nearly abrogated CFTR single channel activity (defined as forskolin-activated Cl currents) in patch clamp studies, effects of which were blocked with toll-like receptor (TLR)-4 inhibitor. Unitary conductance and single-channel amplitude of CFTR were unaffected, but open probability and number of active channels were markedly decreased. LPS increased cytoplasmic and mitochondrial reactive oxygen species resulting in CFTR carbonylation. All effects of exposure were eliminated when reduced glutathione was added in the medium along with LPS. Functional microanatomy parameters, including mucociliary transport, in human sinonasal epithelial cells in vitro were also decreased, but restored with co-incubation with glutathione or TLR-4 inhibitor. In vivo measurements, following application of LPS in the nasal cavities showed significant decreases in transepithelial Cl secretion as measured by nasal potential difference (NPD) - an effect that was nullified with glutathione and TLR-4 inhibitor. These data provide definitive evidence that LPS-generated reactive intermediates downregulate CFTR function in vitro and in vivo which results in cystic fibrosis-type disease. Findings have implications for therapeutic approaches intent on stimulating Cl secretion and/or reducing oxidative stress to decrease the sequelae of GNB airway colonization and infection.
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http://dx.doi.org/10.1016/j.redox.2021.101998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129928PMC
July 2021

COVID-19 International Collaborative Research by the Health Insurance Review and Assessment Service Using Its Nationwide Real-world Data: Database, Outcomes, and Implications.

J Prev Med Public Health 2021 Jan 26;54(1):8-16. Epub 2021 Jan 26.

HIRA Research Institute, Health Insurance Review and Assessment Service, Wonju, Korea.

This article aims to introduce the inception and operation of the COVID-19 International Collaborative Research Project, the world's first coronavirus disease 2019 (COVID-19) open data project for research, along with its dataset and research method, and to discuss relevant considerations for collaborative research using nationwide real-world data (RWD). COVID-19 has spread across the world since early 2020, becoming a serious global health threat to life, safety, and social and economic activities. However, insufficient RWD from patients was available to help clinicians efficiently diagnose and treat patients with COVID-19, or to provide necessary information to the government for policy-making. Countries that saw a rapid surge of infections had to focus on leveraging medical professionals to treat patients, and the circumstances made it even more difficult to promptly use COVID-19 RWD. Against this backdrop, the Health Insurance Review and Assessment Service (HIRA) of Korea decided to open its COVID-19 RWD collected through Korea's universal health insurance program, under the title of the COVID-19 International Collaborative Research Project. The dataset, consisting of 476 508 claim statements from 234 427 patients (7590 confirmed cases) and 18 691 318 claim statements of the same patients for the previous 3 years, was established and hosted on HIRA's in-house server. Researchers who applied to participate in the project uploaded analysis code on the platform prepared by HIRA, and HIRA conducted the analysis and provided outcome values. As of November 2020, analyses have been completed for 129 research projects, which have been published or are in the process of being published in prestigious journals.
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http://dx.doi.org/10.3961/jpmph.20.616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939755PMC
January 2021

A preclinical model to tackle chronic rhinosinusitis.

Int Forum Allergy Rhinol 2021 04 27;11(4):826-827. Epub 2021 Jan 27.

Department of Surgery, School of Medicine, University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.1002/alr.22768DOI Listing
April 2021

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion.

J Ginseng Res 2021 Jan 13;45(1):66-74. Epub 2019 Sep 13.

Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States.

Background: Abnormal chloride (Cl) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl secretion in nasal epithelium.

Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis.

Results: RGAE (at 30μg/mL of ginsenosides) significantly increased Cl transport [measured as change in short-circuit current (ΔI = μA/cm)] when compared with control in WT and CFTR MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔI attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 m vs control, 3.9+/-0.09 m; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz;  < 0.0001) in MNSE.

Conclusion: RGAE augments ASL depth and CBF by stimulating Cl secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.
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http://dx.doi.org/10.1016/j.jgr.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790903PMC
January 2021

Systematic review of anterior congenital cephaloceles: open vs endoscopic repair.

Int Forum Allergy Rhinol 2020 12 27;10(12):1334-1336. Epub 2020 Sep 27.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Anterior cephaloceles are rare congenital malformations that have historically been corrected via open approaches. Although the advent of endoscopic endonasal surgery has provided a minimally invasive and theoretically less morbid approach to the anterior skull base, whether endoscopic approaches provide superior treatment outcomes to open techniques has yet to be elucidated. The objective of this study was to systematically review the available literature regarding presentation and outcomes of open vs endoscopic repair of congenital anterior cephaloceles.

Methods: A systematic review of the PubMed, Embase, CINAHL, and Cochrane databases was performed on January 15, 2020, to identify studies from the past 50 years reporting cases of congenital anterior cephaloceles. Data on gender, age at operation, imaging modality, cephalocele location, operative approach, and intra- and postoperative complications were collected.

Results: Nonduplicated data (153 articles) consisted of 781 patients with congenital anterior encephaloceles. Surgical outcomes were reported in 349 patients (222 open approaches, 127 endoscopic approaches), with an average age of 4.6 years. There was a 1.3:1 male-to-female ratio. Clinical presentation included nasal obstruction (n = 154), hypertelorism (n = 106), and cleft lip/palate (n = 100). Defects were classified as sincipital (n = 479) or basal (n = 257), with 45 patients broadly classified as anterior. The number of complications experienced per operation was 0.13 for endoscopic and 0.44 for open approaches (p < 0.0001). Mortality was significantly lower for the endoscopic group compared with patients treated with open surgery (0.008 vs 0.05, p < 0.05).

Conclusion: Endoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.
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http://dx.doi.org/10.1002/alr.22701DOI Listing
December 2020

Treatment of Frontal Sinus Osteomyelitis in the Age of Endoscopy.

Am J Rhinol Allergy 2021 May 16;35(3):368-374. Epub 2020 Sep 16.

Department of Otolaryngology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.

Objective: Frontal sinus osteomyelitis is a severe complication which can result from chronic rhinosinusitis, trauma, or as a complication of reconstruction or obliteration of the frontal sinus. The objective of the current study is to evaluate the contemporary management of frontal sinus osteomyelitis in light of recent advancements in endoscopic surgical techniques.

Methods: Review of a prospectively collected database of patients with frontal sinus pathology was performed from 2008-2020. Data from individuals with frontal sinus osteomyelitis was collected including demographics, etiology, surgical technique, adjunctive medical treatments, complications, and clinical follow up.

Results: Sixteen patients (average age 48.3, range 8-84) were included in the study. An open approach was utilized in 6 patients (2 osteoplastic flaps, 3 Reidel procedures, 1 cranialization). Seven patients underwent completely endoscopic approaches (3 Draf IIB, 4 Draf III), while 3 individuals had combined procedures (Lynch with Draf III, osteoplastic flap + Draf III, fistula excision + Draf IIb). All patients received 6 weeks of antibiotics. Average clinical follow up was 24.4 months with no patients requiring revision procedures.

Conclusion: Endoscopic, endoscopic-assisted, and open approaches were utilized successfully in the current series of patients with osteomyelitis of the anterior table of the frontal sinus. While the progression of endoscopic techniques allows an additional surgical treatment option, it is important to select patients appropriately as open procedures continue to have an important role in the treatment algorithm.
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http://dx.doi.org/10.1177/1945892420959587DOI Listing
May 2021

Endoscopic Management of Maxillary Sinus Diseases of Dentoalveolar Origin.

Oral Maxillofac Surg Clin North Am 2020 Nov 2;32(4):639-648. Epub 2020 Sep 2.

Department of Otolaryngology-Head & Neck Surgery, University of Alabama at Birmingham, 1155 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35233, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Endoscopic surgery on the maxillary sinus has experienced significant advances in technique and approaches since the maxillary antrostomy was introduced in the 1980s. Disease processes that previously required open surgical approaches to the maxillary sinus can now be treated endoscopically while preserving form and function of the sinus and without injuring the maxillary sinus mucosa or disrupting normal mucociliary clearance. Understanding the techniques described in this article will allow surgeons to appropriately plan treatment strategies for patients with a variety of maxillary sinus diseases from dentoalveolar origin.
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http://dx.doi.org/10.1016/j.coms.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541637PMC
November 2020

Antibiotic eluting sinus stents.

Laryngoscope Investig Otolaryngol 2020 Aug 11;5(4):598-607. Epub 2020 Jul 11.

Department of Otolaryngology Head and Neck Surgery University of Alabama at Birmingham Birmingham Alabama USA.

Objectives: Chronic rhinosinusitis (CRS) is a multifactorial disease affecting up to 16% of the United States population and disproportionately affecting the cystic fibrosis (CF) patient population. Despite treating the underlying infection, the use of systemic antibiotics has shown little efficacy in alleviation of symptom burden. This review seeks to discuss recent research on novel antibiotic eluting stent therapy in vitro and within animal models as well as the factors that contribute to its efficacy.

Data Sources: PubMed literature review.

Review Methods: A review of all published literature related to antibiotic eluting sinus stents was conducted to integrate and summarize this innovative approach to chronic sinus infections.

Results: Placement of the ciprofloxacin sinus stent (CSS) and ciprofloxacin-ivacaftor sinus stent (CISS) exhibited improvement in endoscopic and radiographic findings in rabbit CRS models. While the CSS showed an overall trend toward improvement in microscopic findings and a reduction in biofilm mass, there remained a significant quantity of planktonic bacteria due to antibiotic depletion from an initial burst release in the first 48 hours of stent placement. The CISS and ciprofloxacin-azithromycin sinus stents (CASSs) exhibited controlled antibiotic release over the study period leading to greatly reduced planktonic bacterial load and biofilm mass. In vitro studies indicate that CASS may be just as efficacious at reducing biofilm mass.

Conclusion: Antibiotic eluting sinus stents show significant promise as a novel therapeutic strategy for CRS. The CISS may have particular promise for the CF patient population by addressing both the infectious and genetic components of disease. Animal studies demonstrate significant promise for translation into human studies. Human clinical trials are warranted to determine the efficacy of antibiotic sinus stents in human patients.

Level Of Evidence: NA.
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http://dx.doi.org/10.1002/lio2.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444760PMC
August 2020

Contribution of Short Chain Fatty Acids to the Growth of in Rhinosinusitis.

Front Cell Infect Microbiol 2020 11;10:412. Epub 2020 Aug 11.

Department of Otolaryngology Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, United States.

Chronic rhinosinusitis (CRS) is characterized by complex bacterial infections with persistent inflammation. Based on our rabbit model of sinusitis, blockage of sinus ostia generated a shift in microbiota to a predominance of mucin degrading microbes (MDM) with acute inflammation at 2 weeks. This was followed by conversion to chronic sinus inflammation at 3 months with a robust increase in pathogenic bacteria (e.g., ). MDMs are known to produce acid metabolites [short chain fatty acids (SCFA)] that have the potential to stimulate pathogen growth by offering a carbon source to non-fermenting sinus pathogens (e.g., ). The objective of this study is to evaluate the concentrations of SCFA within the mucus and its contribution to the growth of . Healthy and sinusitis mucus from the rabbit model were collected and co-cultured with the PAO1 strain of for 72 h and colony forming units (CFUs) were determined with the targeted quantification of three SCFAs (acetate, propionate, butyrate). Quantification of SCFAs in healthy and sinusitis mucus from patients with was also performed via high performance liquid chromatography. To provide evidence of fermentative activity, SCFAs were quantified within the mucus samples from rabbits with and without sinusitis. Acetate concentrations were significantly greater in sinusitis mucus compared to controls (4.13 ± 0.53 vs. 1.94 ± 0.44 mM, < 0.01). After 72 h of co-culturing mucus samples with PAO1 in the presence of mucin medium, the blue-green pigment characteristic of was observed throughout tubes containing sinusitis mucus. CFUs were higher in cultures containing mucus samples from sinusitis (8.4 × 10 ± 4.8 × 10) compared to control (1.4 × 10 ± 2.0 × 10) or no mucus (1.5 × 10 ± 2.1 × 10) ( < 0.0001). To provide evidence of fermentative activity in human CRS with , the presence of SCFAs in human mucus was analyzed and all SCFAs were significantly higher in CRS with compared to controls ( < 0.05). Given that SCFAs are solely derived from bacterial fermentation, our evidence suggests a critical role for mucin-degrading bacteria in generating carbon-source nutrients for pathogens. MDM may contribute to the development of recalcitrant CRS by degrading mucins, thus providing nutrients for potential pathogens like .
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http://dx.doi.org/10.3389/fcimb.2020.00412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431473PMC
June 2021

An Expedited Intracranial Pressure Monitoring Protocol Following Spontaneous CSF Leak Repair.

Laryngoscope 2021 02 14;131(2):E408-E412. Epub 2020 Aug 14.

Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.

Objective: Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks.

Methods: Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short-term success of skull base repair, complications, hospital length of stay, and cost-based analysis.

Results: Fifty-five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18).

Conclusion: An expedited monitoring protocol shortened hospital stay without increased risk of complications.

Level Of Evidence: III Laryngoscope, 131:E408-E412, 2021.
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http://dx.doi.org/10.1002/lary.28929DOI Listing
February 2021

Azithromycin and ciprofloxacin inhibit interleukin-8 secretion without disrupting human sinonasal epithelial integrity in vitro.

Int Forum Allergy Rhinol 2021 02 28;11(2):136-143. Epub 2020 Jul 28.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: We recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti-inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs).

Methods: Pseudomonas aeruginosa lipopolysaccharide (LPS)-stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin-8 (IL-8) secretion was quantified by enzyme-linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance [TEER], paracellular permeability [fluorescein isothiocyanate-labeled dextran], lactate dehydrogenase [LDH] assays) and function (ciliary beat frequency [CBF]) were also evaluated.

Results: Azithromycin significantly reduced secreted IL-8 from P. aeruginosa LPS-stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin [6 μg/mL] = 4.58 ± 0.40 ng/mL, azithromycin [60 µg/mL] = 4.31 ± 0.06, azithromycin [180 µg/mL] = 4.27 ± 0.26 ng/mL, p < 0.05). Co-incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS-stimulated HSNECs also displayed a significant reduction in secreted IL-8 when compared to P. aeruginosa LPS alone (co-treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function.

Conclusion: Azithromycin decreased P. aeruginosa LPS IL-8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti-inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS.
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http://dx.doi.org/10.1002/alr.22656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854841PMC
February 2021

Differential Chloride Secretory Capacity in Transepithelial Ion Transport Properties in Chronic Rhinosinusitis.

Am J Rhinol Allergy 2020 Nov 23;34(6):830-837. Epub 2020 Jun 23.

Department of Otolaryngology-Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Epithelial ion transport regulates hydration of airway mucosal surfaces, and thus promotes effective mucociliary clearance (MCC). Decreased transepithelial Cl transport may contribute to epithelial dysfunction by abrogating MCC and increasing mucus viscosity in chronic rhinosinusitis (CRS). The objective of the current study is to evaluate Cl channel transport properties from cultures of human sinonasal epithelia.

Methods: Human sinonasal epithelia (HSNE) from patients undergoing sinus surgery were cultured at an air-liquid interface to confluence and full differentiation. The epithelial monolayers were mounted in Ussing Chambers to investigate pharmacological manipulation of ion transport. Epithelial Na channel (via Amiloride), CFTR (via forskolin), and Ca-activated Cl channel (CaCC, via UTP) transport were investigated among three different patient groups: Control, CRS and CRS with polyposis. CFTR mRNA levels were evaluated with quantitative RT-PCR.

Results: HSNE cultures from 18 patients (Control = 9, CRS = 6, CRS with polyposis = 3) were evaluated in 142 experiments. Summary data from the 18 patients demonstrated that stimulated CFTR-mediated anion transport (Δ I) was significantly lower with CRS (7.58+/-2.24 µA/cm) compared to control (25.86+/-3.44 µA/cm) and CRS with polyposis (20.16+/-4.0 µA/cm) (p = 0.004). No statistically significant difference was found for CaCC anion transport between groups (p = 0.39). Significantly decreased mRNA (relative expression) was noted in CRS cultures (CRS = 40.83+/-1.76 vs. control = 116.2+/-24.27, p = 0.03).

Conclusions: A substantial decrease in the Cl secretory capacity of HSNE monolayers was demonstrated in CRS subjects. Data suggest that CFTR may contribute more to abnormal ion transport in CRS than CaCC.
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http://dx.doi.org/10.1177/1945892420930975DOI Listing
November 2020

The SARS-CoV-2 pandemic impact on rhinology research: A survey of the American Rhinologic Society.

Am J Otolaryngol 2020 Sep - Oct;41(5):102617. Epub 2020 Jun 18.

Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, United States of America.

Background: The COVID-19 pandemic has radically shifted healthcare operations within hospitals and universities across the globe. However, the effect of the COVID-19 pandemic on research endeavors and clinical trials is unclear.

Objective: This study investigates the impact of the COVID-19 pandemic on basic science and clinical research within the rhinology community.

Methods: A cross-sectional study was designed utilizing an 8-question survey to identify changes to rhinology research. Questions evaluated the impact of the COVID-19 pandemic on administrative research support and staffing, basic science research, clinical trials and resident research involvement.

Results: Seventy-one participants responded to the survey (8.5% response rate). Most respondents noted changes in IACUC/IRB approval (faster, 33%; slower, 31%). Of those who employed laboratory personnel, 64% were able to continue staff employment with full salary. The majority of animal research and in vitro studies were halted (64% and 56%, respectively), but animal care and cell line maintenance were allowed to continue. Clinical trial enrollment was most commonly limited to COVID derived studies (51%). Forty-seven percent of respondents noted increased resident research participation.

Conclusion: The rapid spread of the SARS-CoV-2 virus has markedly impacted rhinology-related research. Maintaining safe workplace practices as restrictions are lifted will hopefully mitigate the spread of the virus and allow research productivity to resume.
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http://dx.doi.org/10.1016/j.amjoto.2020.102617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301141PMC
September 2020

Phenotypes in Chronic Rhinosinusitis.

Curr Allergy Asthma Rep 2020 05 19;20(7):20. Epub 2020 May 19.

Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, 1720 Second Avenue South, Birmingham, AL, 35294, USA.

Purpose Of Review: Chronic rhinosinusitis (CRS) is a heterogenous disease process affecting a significant proportion of the population and impacting quality of life and productivity. Historically, CRS has been classified broadly into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Increased understanding regarding unique presentations of CRS subsets and their underlying inflammatory profiles has led to a new system for classifying CRS phenotypes.

Recent Findings: Consideration of CRS phenotypes has traditionally been a key factor in determining treatment paradigms. Under a new phenotype classification system, physical findings will continue to drive treatment decisions, but with more precision. Recent rapidly accumulated knowledge indicates that the broad categorization of CRSwNP or CRSsNP is no longer clinically useful. Reorganization of CRS phenotypes and their underlying endotypes will lead to more targeted and efficacious therapy.
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http://dx.doi.org/10.1007/s11882-020-00916-6DOI Listing
May 2020

The Microbiome and Chronic Rhinosinusitis.

Immunol Allergy Clin North Am 2020 05 16;40(2):251-263. Epub 2020 Jan 16.

Department of Otolaryngology-Head and Neck Surgery, University of Colorado, 12631 East 17th Avenue, B205, Aurora, CO 80045, USA. Electronic address:

Chronic rhinosinusitis (CRS) is persistent inflammation and/or infection of the nasal cavity and paranasal sinuses. Recent advancements in culture-independent molecular techniques have enhanced understanding of interactions between sinus microbiota and upper airway microenvironment. The dysbiosis hypothesis-alteration of microbiota associated with perturbation of the local ecological landscape-is suggested as a mechanism involved in CRS pathogenesis. This review discusses the complex role of the microbiota in health and in CRS and considerations in sinus microbiome investigation, dysbiosis of sinus microbiota in CRS, microbial interactions in CRS, and development of preclinical models. The authors conclude with future directions for CRS-associated microbiome research.
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http://dx.doi.org/10.1016/j.iac.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154041PMC
May 2020

Current management of congenital anterior cranial base encephaloceles.

Int J Pediatr Otorhinolaryngol 2020 Apr 8;131:109868. Epub 2020 Jan 8.

Departments of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Objectives: Congenital encephaloceles provide unique diagnostic and reconstructive challenges for the pediatric rhinologist. The objectives of the current study were to evaluate contemporary treatment strategies for congenital encephaloceles focusing on presentation, surgical technique, and outcomes.

Methods: Multi-institutional retrospective chart review of congenital encephaloceles (2003-2019). Data regarding demographics, presenting symptoms, associated abnormalities, surgical technique, size, location, and complications were collected.

Results: Fourteen patients with 15 congenital encephaloceles were treated using endoscopic techniques (avg 6.0 years, range 2 months-22 years) with mean follow up of 23 months. The majority presented with nasal obstruction (n = 13); only one child had cerebrospinal fluid (CSF) rhinorrhea. Associated anomalies included nasal deformities, congenital hypopituitarism, and Morning Glory syndrome. Average encephalocele size was 2.44 cm (range 0.5-3.6 cm) with mean skull base defect size of 8.6 x 7.7 mm. Locations included the foramen cecum (n = 9), central sphenoid (n = 3), midline anterior cranial fossa (n = 1), orbital plate of frontal bone (n = 1), and ethmoid roof (n = 1). Because of favorable expansion from encephaloceles, it was unnecessary to postpone surgeries to allow nasal cavity growth. Three individuals had prior operations, including surgeries for "nasal polyp" or "adenoid cyst". Two patients had post-operative complications (meningitis and CSF leak) effectively treated with no further sequelae.

Conclusions: In the current study, congenital encephaloceles in children as young as 2 months were successfully repaired using endoscopic techniques. Endoscopic approaches remain a safe and effective intervention for management of these lesions.
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http://dx.doi.org/10.1016/j.ijporl.2020.109868DOI Listing
April 2020

The impact of Lactococcus lactis (probiotic nasal rinse) co-culture on growth of patient-derived strains of Pseudomonas aeruginosa.

Int Forum Allergy Rhinol 2020 04 10;10(4):444-449. Epub 2020 Jan 10.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: The Lactococcus strain of bacteria has been introduced as a probiotic nasal rinse for alleged salubrious effects on the sinonasal bacterial microbiome. However, data regarding interactions with pathogenic bacteria within the sinuses are lacking. The purpose of this study is to assess the interaction between L. lactis and patient-derived Pseudomonas aeruginosa, an opportunistic pathogen in recalcitrant chronic rhinosinusitis (CRS).

Methods: Commercially available probiotic suspension containing L. lactis W136 was grown in an anaerobic chamber and colonies were isolated. Colonies were co-cultured with patient-derived P. aeruginosa strains in the presence of porcine gastric mucin (mimicking human mucus) for 72 hours. P. aeruginosa cultures without L. lactis served as controls. Colony forming units (CFUs) were compared.

Results: Six P. aeruginosa isolates collected from 5 CRS patients (3 isolates from cystic fibrosis [CF], 1 mucoid strain) and laboratory strain PAO1 were co-cultured with L. lactis. There was no statistical difference in CFUs of 5 P. aeruginosa isolates grown with L. lactis compared to CFUs without presence of L. lactis. CFU counts were much higher when the mucoid strain was co-cultured with L. lactis (CFU = 1.9 × 108 ± 1.44 × 107, CFU = 1.3 × 108 ± 8.9 × 106, p = 0.01, n = 7). L. lactis suppressed the growth of 1 P. aeruginosa strain (CFU = 2.15 × 108 ± 2.9 × 107, CFU = 3.95 × 108 ± 4.8 × 106, p = 0.03, n = 7).

Conclusion: L. lactis suppressed the growth of 1 patient P. aeruginosa isolate and induced growth of another (a mucoid strain) in in vitro co-culture setting in the presence of mucin. Further experiments are required to assess the underlying interactions between L. lactis and P. aeruginosa.
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http://dx.doi.org/10.1002/alr.22521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058912PMC
April 2020

Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis.

Int Forum Allergy Rhinol 2020 04 23;10(4):481-488. Epub 2019 Dec 23.

Department of Otolaryngology-Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor-releasing biodegradable sinus stent (CISS)-a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis.

Methods: Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly-D/L-lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in-vivo sinus potential difference (SPD) assay.

Results: Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, -5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2-log reduction of PAO1 was observed (control, -2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl transport in the CISS group compared with the control group (Cl -free + forskolin ΔPD: control, -4.23 ± 1.04 mV; CISS, -18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals.

Conclusion: The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double-layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis.
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http://dx.doi.org/10.1002/alr.22514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182488PMC
April 2020

Frontal sinus fractures and cerebrospinal fluid leaks: a change in surgical paradigm.

Curr Opin Otolaryngol Head Neck Surg 2020 Feb;28(1):52-60

Department of Otolaryngology Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Purpose Of Review: Traditionally, frontal sinus trauma has been treated using open incisions to access the anterior and/or posterior table. Mounting evidence indicates frontal sinus trauma can be managed using an endoscopic endonasal approach (EEA) with less morbidity. Such an approach permits preservation of a functional sinus and less reliance on computed tomography for postoperative follow up. The goal of this article is to highlight a shift in paradigm away from open approaches using external incisions towards an EEA to repair cerebrospinal fluid (CSF) leaks and fractures of the frontal sinus.

Recent Findings: In a prospective case series of 46 patients undergoing EEA to frontal sinus fractures, 41 patients had active CSF leaks arising from the posterior table of the frontal sinus. A successful endoscopic repair was achieved in 97.6% with only one patient requiring revision Draf IIB surgery. Anterior table fractures were also successfully reduced with excellent cosmesis.

Summary: Endoscopic repair of frontal sinus fractures and CSF leaks is effective and well tolerated. In select patients, it is the preferred treatment as it maintains normal sinus structure and function, minimizing both early and late complications.
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http://dx.doi.org/10.1097/MOO.0000000000000602DOI Listing
February 2020

In-vitro evaluation of a ciprofloxacin and azithromycin sinus stent for Pseudomonas aeruginosa biofilms.

Int Forum Allergy Rhinol 2020 01 6;10(1):121-127. Epub 2019 Nov 6.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin-azithromycin sinus stent (CASS) in vitro.

Methods: The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly-l-lactic acid (PLLA) stent. In-vitro evaluation included: (1) assessment of drug-coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti-biofilm activities against Pseudomonas aeruginosa.

Results: The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reduced P aeruginosa biofilm mass compared with bare stents and controls (relative optical density units at 590-nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000; p < 0.001; n = 3).

Conclusion: The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti-biofilm activities against P aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.
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http://dx.doi.org/10.1002/alr.22475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942221PMC
January 2020

Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia.

Int Forum Allergy Rhinol 2019 12 20;9(12):1430-1435. Epub 2019 Aug 20.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Mucociliary clearance is a main defense mechanism of the airway and is impaired in ciliary dyskinesia. The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia.

Methods: Bronchiectasis patients referred to a rhinology clinic for nasal brush biopsy (NBB) were included in this study. NBB was performed using a curettage technique whereby ciliated epithelial cells were obtained from the surface of the inferior nasal turbinate. Results of transmission electron microscopy findings, primary ciliary dyskinesia (PCD) gene (35 genes) analyses (Invitae), and sinus computed tomography (CT) scans were reviewed.

Results: Twenty-three patients (age, 54 ± 2.9 years) were referred for NBB between 2015 and 2018. Thirteen patients (56.5%) met the criteria for diagnosis of CRS. Nineteen patients had ciliary ultrastructural defects. The most common finding was compound cilia (n = 11, 47.8%). Five patients (21.7%) had central microtubule defects (CMD) with higher forced expiratory volume in 1 second (FEV ) at the time of referral than those without CMD (CMD , 91 ± 3.7%; CMD , 73.5 ± 5.7%; p = 0.023). Of 15 subjects with a PCD gene panel, 67% (9 of 15) carried at least 1 gene associated with PCD. Only 1 patient reached diagnosis of PCD. Approximately 50% of non-PCD carriers had a smoking history (p < 0.05). Lund-Mackay scores did not significantly differ between PCD and non-PCD carriers (p = 0.72).

Conclusion: Nearly half of bronchiectasis patients referred for NBB had concurrent CRS. The presence of ciliary abnormalities was not amplified in bronchiectasis patients with CRS compared to those without CRS. Extrinsic factors may be related to ciliary structural abnormalities in non-PCD gene carriers.
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http://dx.doi.org/10.1002/alr.22414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901752PMC
December 2019

Validation of the Maxillary Sinus Roof as a Landmark for Navigating the Pediatric Skull Base.

Ann Otol Rhinol Laryngol 2020 Jan 9;129(1):12-17. Epub 2019 Aug 9.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.

Objective: To define a new anatomic relationship in pediatric sinus surgery, assessing the maxillary roof as a constant safe landmark to avoid skull base injury in the pediatric population.

Study Design: Retrospective analysis.

Setting: Tertiary care children hospital.

Subjects And Methods: A retrospective analysis was performed of all computed tomography scans of the sinuses and facial bones at the emergency department of a tertiary children's hospital over the course of a year. Radiographic measurements included the lowest cribriform plate and planum sphenoidale (PS) heights, or posterior skull base when not yet pneumatized, as well as the highest maxillary roof height. The nasal floor was used for reference. Statistics were performed via Shapiro-Wilks test with a -value of .05 indicating statistical significance.

Results: Three hundred and seven unique scans were reviewed (38.9% female; n = 122;  = .58). Age stratification was based on previously described sinus growth patterns. In all patients, the maximum maxillary height was inferior to the lowest measured cribriform lamella and PS ( < .001; CI, 98.5%-99%). Inter- and intrarater reliability and accuracy were verified through blinded review and re-review (ρ = .99 and .98 respectively,  ≤ .001). The validity of sole coronal measurements due to incomplete sagittal reformatting was also confirmed (ρ = 1.00,  ≤ .001).

Conclusion: Despite variation in sinus growth and development in children, the current study demonstrated the validity of the maxillary sinus roof as a constant safe landmark in the pediatric population, offering a novel anatomic relationship for teaching safety in performing pediatric sinus surgery.

Level Of Evidence: 4.
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http://dx.doi.org/10.1177/0003489419867967DOI Listing
January 2020
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