Phenotypes in Chronic Rhinosinusitis.

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.

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

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.

Antimicrobial stewardship in the Federal Bureau of Prisons: Approaches from the national and local levels.

OBJECTIVES: To determine the impact of national and local antimicrobial stewardship measures on overall antibiotic prescribing in the Federal Bureau of Prisons (BOP). SETTING: Care was delivered to more than 160,000 inmates in 122 BOP facilities in the United States and Puerto Rico. PRACTICE DESCRIPTION: Medical centers and health services clinics staffed by in-house medical staff, consultants, and specialists. Staffs include a variety of disciplines, including physicians, pharmacists, dentists, nurses, infection control personnel, therapists, health services administrators, and institution executive staff. PRACTICE INNOVATION: Innovations occurred on 2 levels: local components were used to reinforce national initiatives. Local institutions used a multidisciplinary team approach including education and focused evaluations of all antibiotic prescriptions before dispensing. National initiatives included the development of a closed formulary, clinical practice guidelines, an antimicrobial stewardship group led by pharmacy, development of tools and strategies for institutions, inclusion in the BOP strategic plan, and a drug utilization evaluation. EVALUATION: This was a study of antimicrobial stewardship within BOP and the resultant impact on antibiotic prescriptions. In addition, one institution's antimicrobial stewardship methods were reviewed to determine the impact on antibiotic prescribing practices. RESULTS: The total number of antibiotic prescriptions in BOP-managed institutions in fiscal year (FY) 2010 (October 2009 to September 2010) was 142,907 and progressively decreased to 105,832 in FY2015. The number of antibiotic prescriptions per 1000 inmates correspondingly decreased from 829 in FY2010 to 625 in FY2015. The overall number of antibiotic prescriptions as a percentage of total prescriptions decreased from 7.64% in FY2010 to 5.84% in FY2015. CONCLUSION: A robust multidisciplinary antimicrobial stewardship program has likely contributed to a decrease in both the total number and the rate of antibiotic prescriptions on a per-1000-patient basis in BOP.

Plate fixation for management of plantar instability of the distal tarsus/proximal metatarsus in 5 horses.

OBJECTIVE: To report plate fixation for management of traumatic injuries resulting in plantar instability of the proximal intertarsal (PIT) and tarsometatarsal (TMT) joints. STUDY DESIGN: Case series. MATERIALS AND METHODS: Medical records (October 1988 to August 2007) of horses that had internal fixation of the distal aspect of the tarsus were reviewed. Horses that had a broad dynamic compression plate (DCP) or broad locking compression plate (LCP) applied on the plantar-lateral aspect of the tarsus extending from the proximal calcaneus to the proximal one third of the metatarsus were included. Signalment, clinical signs, radiographic findings, time to surgery, implant type, postoperative management and complications were recorded. Long-term (>1 year) outcome was obtained for 4 horses. RESULTS: Five horses were treated, 4 had DCP fixation and 1 had LCP fixation. Subluxation of the proximal intertarsal joint was treated in 3 horses and 2 horses had fractures of the distal tarsal bones or proximal aspect of the metatarsus. Perioperative complications included peroneus tertius rupture (2 horses) and postoperative infection.(1) Four horses were discharged and 1 year after surgery were considered sound at pasture; 3 horses were sound enough for limited riding. CONCLUSIONS: Plate fixation provides adequate strength and stability for successful management of injuries that result in plantar instability of the tarsus and proximal metatarsus.

Long-duration pain block for postoperative anesthesia after endoscopic sinus surgery.

KEY POINTS: A long-duration pain block did not decrease postoperative pain or opioid consumption. Extended sinus procedures do not lead to additional postoperative pain or opioid consumption.

Postoperative Gabapentin's Effect on Opioid Consumption and Pain Control Following Sinonasal Surgery.

OBJECTIVE: This study investigates the impact of postoperative gabapentin on opioid consumption and pain control following endoscopic sinus surgery (ESS) and/or septoplasty. METHODS: Patients who underwent ESS and/or septoplasty at a single institution from 2021 to 2022 were enrolled. All patients received postoperative hydrocodone-acetaminophen for pain control. Half of the patients were also prescribed gabapentin for the first postoperative day in addition to hydrocodone-acetaminophen. Subjects completed the Revised American Pain Society Patient Outcome Questionnaire 24 h and 7 days after surgery. We conducted a multivariable regression analysis to assess opioid consumption and improvement in pain scores in the first week between gabapentin and non-gabapentin groups. RESULTS: A total of 102 subjects, 51 in each arm, were enrolled. The mean age was 52 years and 53% of participants were female. Controlling for important baseline demographic, clinical, and surgically related variables, the addition of postoperative gabapentin was associated with a 44% (9.5 mg from 21.6 mg) reduction in opioids consumed in the first postoperative week (B = -9.54, 95% C.I. = [-17.84, -1.24], p = 0.025). In addition, patients in both arms exhibited similar improvement in pain severity and sleep interference in the first 7 days (B = -1.59, 95% C.I. = [-5.03, 1.84], p = 0.36). CONCLUSION: To the best of our knowledge, this is the first study to investigate the impact of postoperative gabapentin on opioid consumption and pain control following ESS and/or septoplasty. Our analysis demonstrated that postoperative gabapentin effectively reduced opioid use during the first postoperative week without compromising pain control. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1065-1072, 2023.

Endoscopic Management of a Post-Traumatic Internal Maxillary Artery Pseudoaneurysm: Case Report and Review of the Literature.

Internal maxillary artery (IMA) pseudoaneurysms are rare, and typically occur following trauma or orthognathic surgery. Pseudoaneurysms are life-threatening conditions, and expeditious workup and treatment is critical. Endoscopic treatment of an IMA pseudoaneurysm is a feasible option and should be considered when IR embolization is not available. The objective of this study is to review the literature on IMA pseudoaneurysms and present the first reported case of an IMA pseudoaneurysm successfully treated endoscopically.

Role of High-Risk HPV Detected by PCR in Malignant Sinonasal Inverted Papilloma: A Meta-Analysis.

INTRODUCTION: Prior studies suggest that there may be a link between human papillomavirus (HPV) infection and malignant sinonasal inverted papilloma (SNIP). This systematic review and meta-analysis was performed to further evaluate this potential association. STUDY DESIGN: Systematic review with meta-analysis. METHODS: The Medline and Embase databases were used to identify case-control studies reporting the risk of malignant SNIP in patients with high-risk HPV subtypes identified by polymerase chain reaction (PCR). Meta-analysis was performed to determine pooled odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Twenty-one studies were identified, including a total of 841 subjects with SNIP. Seventeen studies were included in the final analysis, as four studies did not have any HPV-positive tumors in either group. A total of 56 malignant SNIP and 551 benign SNIP were ultimately identified. The pooled log-OR was 1.80 (95% CI: 1.03-2.57) for all high-risk HPV subtypes. Stratification by high-risk HPV subtype showed a log-OR of 1.67 (95% CI: 0.88-2.46) for HPV-16 and log-OR of 2.68 (95% CI: 1.30-4.05) for HPV-18. CONCLUSION: Infection with high-risk HPV subtypes may be associated with an increased risk of malignant SNIP. HPV-18 showed the greatest overall average effect size of the common high-risk subtypes. LEVEL OF EVIDENCE: NA Laryngoscope, 132:926-932, 2022.

Triamcinolone-impregnated bioabsorbable middle meatus packing following endoscopic sinus surgery: A prospective randomized controlled trial.

INTRODUCTION: Topical steroids are a mainstay in the treatment of chronic rhinosinusitis (CRS). Multiple delivery methods of topical steroids following sinus surgery have been investigated. The purpose of this trial is to evaluate the effect of triamcinolone-impregnated absorbable nasal packing on healing following endoscopic sinus surgery (ESS). METHODS: This is a prospective, randomized, double-blind, placebo-controlled trial. A total of 22 subjects (14 without polyps and eight with polyps) were enrolled and were randomized to receive triamcinolone-impregnated packing in one sinus cavity and normal saline-soaked packing in the contralateral sinus cavity. Endoscopic evaluation was completed at the first two postoperative visits, and Lund-Kennedy (LK) endoscopic scores and perioperative sinus endoscopy (POSE) scores were calculated at each visit. RESULTS: The results of this study found no significant difference in the appearance of the sinuses at either postoperative visit. Mean LK scores for the triamcinolone and saline groups at the first and second postoperative visits were 2.09 ± 1.23 versus 2.18 ± 1.01 (p = 0.79) and 1.79 ± 1.08 versus 1.68 ± 1.16 (p = 0.77), respectively. POSE scores were 2.59 ± 1.71 versus 2.68 ± 1.62 (p = 0.86) and 1.74 ± 1.15 versus 1.95 ± 1.22 (p = 0.59). CONCLUSION: The results of this study demonstrated no significant difference in healing, crusting, polyps, edema, or secretions between the triamcinolone-treated and non-triamcinolone-treated sinuses. There were no adverse effects from the use of triamcinolone-impregnated absorbable packing. Further studies will be necessary to determine the impact of triamcinolone-impregnated absorbable packing following ESS.

Modified Endoscopic Denker's Approach for Management of Anterior Maxillary Sinus Tumors: Multicenter Series of 58 Cases.

OBJECTIVES: Tumors involving the anterior portion of the maxillary sinus remain technically challenging to access via an endoscopic approach. The modified endoscopic Denker's (MED) procedure was recently introduced to address such lesions. We present a multicenter series of 58 patients with tumors involving the anterior maxillary sinus successfully resected using a MED procedure and present the clinical outcomes and complications. METHODS: A multi-institution retrospective chart review was performed on patients who underwent the MED approach for the management of tumors involving the anterior maxillary sinus from 2009 to 2020. Demographic data, pathology, surgical outcomes, and complications were reviewed. RESULTS: Fifty-eight patients were identified, including 34 (58.6%) male and 24 (41.4%) female patients. The most common pathologies included: inverted papilloma (n = 27; 46.6%), adenoid cystic carcinoma (n = 9; 15.5%), and squamous cell carcinoma (n = 8; 13.8%). Thirty-eight patients (65.5%) underwent MED alone, while 20 (34.5%) had combined expanded endonasal approaches for lesions extending beyond the maxillary sinus. All maxillary sinus lesions were successfully accessed with the MED procedure without the need for an additional approach. After a mean follow-up of 30 months (range, 1-127), 8 of 58 (13.8%) patients developed complications related to the MED, including epiphora requiring an additional procedure (n = 4; 6.9%), prolonged facial/palatal numbness (n = 3; 5.2%), severe epistaxis (n = 1; 1.7%), and vestibular stenosis (n = 1; 1.7%), the latter of which occurred following postoperative radiation. CONCLUSION: The MED procedure is a safe and highly effective approach for benign and malignant tumors involving the anterior maxillary sinus. However, patients should be counseled preoperatively on potential complications including the risk of facial numbness and epiphora.

Insights into the Implications of Coexisting Type 2 Inflammatory Diseases.

The role of type 2 inflammation in the pathogenesis of certain human diseases is an area of active investigation. Certain asthma, atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis phenotypes are characterized by a Th2 predominant inflammatory pathway and are frequently associated with comorbid conditions in patients. The purpose of this article is to review the evidence behind concurrent Th2-mediated diseases and explore how the presence of these comorbid conditions affect patient and disease outcomes.

Tension Pneumocephalus Following Balloon Sinuplasty.

Balloon sinus dilation (BSD) is a common method of relieving sinus outflow obstruction. With the rising utilization of BSD, increasing numbers of BSD-related complications have also been reported. Here, we report a case of pneumocephalus and cerebrospinal fluid leak following BSD of the frontal sinus. Additionally, a review of the literature regarding BSD complications was performed.

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

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.

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

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 Ca2+-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 ISC) was significantly lower with CRS (7.58+/-2.24 µA/cm2) compared to control (25.86+/-3.44 µA/cm2) and CRS with polyposis (20.16+/-4.0 µA/cm2) (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.

Endoscopic Management of Maxillary Sinus Diseases of Dentoalveolar Origin.

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.

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

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.

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

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.

Lateral nasal wall extension of the nasoseptal flap for skull-base and medial orbital wall defects.

BACKGROUND: Sinonasal and skull-base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull-base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull-base and medial orbital wall defects. METHODS: An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull-base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale. RESULTS: Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks). CONCLUSION: The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull-base defects and simultaneous medial orbital wall defects.

Ivacaftor improves rhinologic, psychologic, and sleep-related quality of life in G551D cystic fibrosis patients.

BACKGROUND: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that improves pulmonary function in cystic fibrosis (CF) patients with at least 1 copy of the G551D CFTR mutation. The purpose of this study is to evaluate the impact of ivacaftor on chronic rhinosinusitis (CRS) symptoms in this population. METHODS: The G551D Observational (GOAL) study was a multicenter prospective cohort study enrolling CF patients ≥6 years with at least 1 G551D mutation. Subjects were provided 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaires prior to ivacaftor therapy and at 1, 3, and 6 months afterward. The impact on rhinologic (R), psychological (P), sleep (S), and ear/facial (E) quality of life (QOL) domains was evaluated separately. RESULTS: Of 153 subjects, 129 (84%) completed all questionnaires. Typical baseline symptom burden was low (75% with scores <1) and degree of improvement (ie, reduced scores) was greater with higher baseline scores. SNOT-20 decreased, reflecting improvement, at all follow-up intervals (1 month: [mean change ± standard deviation] -0.25 ± 0.53, p < 0.01; 3 months; -0.29 ± 0.58, p < 0.01; 6 months: -0.21 ± 0.58, p = 0.02), but less than the prespecified minimal clinically important difference (0.8). Significant improvement was observed at 1, 3, and 6 months in the R domain (1 month: -0.24, p < 0.01; 3 months: -0.34, p < 0.01; 6 months: -0.25, p < 0.01) and P domain (1 month: -0.25, p < 0.01; 3 months: -0.32, p < 0.01; 6 months: -0.26, p < 0.01), and 1 and 3 months in the S domain (1 months: -0.35, p < 0.01; 3 months: -0.32, p < 0.01; 6 months: -0.18, p = 0.07). There was no improvement in the E domain at any time point. CONCLUSION: Ivacaftor improves QOL in the R, P, and S domains in G551D CF patients, although QOL instruments validated for CRS may not translate well to CF CRS patients because symptom burden was surprisingly low.

Ivacaftor, a Cystic Fibrosis Transmembrane Conductance Regulator Potentiator, Enhances Ciprofloxacin Activity Against Pseudomonas aeruginosa.

BACKGROUND: Methods to improve the clinical efficacy of currently available antibiotics against multidrug resistant bacteria in cystic fibrosis (CF) chronic rhinosinusitis (CRS) are greatly needed. Ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, was recently identified as having potentially beneficial off-target effects as a weak inhibitor of bacterial DNA gyrase and topoisomerase IV. The objective of the current study is to evaluate whether ivacaftor enhances the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa. METHODS: The planktonic growth of the PAO-1 strain of P. aeruginosa was studied in the presence of ciprofloxacin and/or ivacaftor. Effects were measured according to optical density of cultured PAO-1 at 600 nm. For a static PAO-1 biofilm assay, the PAO-1 strain was inoculated and cultured for 72 h in the presence of the drugs. Formed PAO-1 biofilms were quantified by crystal violet staining and imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). RESULTS: PAO-1 growth was significantly reduced in the presence of ivacaftor (8 or 16 µg/mL) and ciprofloxacin (0.02 or 0.05 µg/mL) compared to ciprofloxacin alone ( P < .001). Similarly, ivacaftor (8 or 16 µg/mL) showed a significant reduction of PAO-1 biofilms when treated with 0.05 µg/mL of ciprofloxacin. Significant synergism was noted between ciprofloxacin and 16 µg/mL of ivacaftor ( P < .0001) in reducing planktonic growth and biofilm formation. Quantitative measurements with crystal violet staining were correlated to CLSM and SEM images. CONCLUSION: Ivacaftor enhanced ciprofloxacin's antimicrobial activity against P. aeruginosa. Further studies evaluating the efficacy of ivacaftor/ciprofloxacin combination for P. aeruginosa for CF CRS are warranted.