Adverse events of biological therapy in chronic rhinosinusitis with nasal polyps: A systematic review.

The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment modalities impact the quality of patients' lives. Monoclonal antibody treatment has recently been used successfully in CRS with limited reported adverse events. We aimed to review the literature to shed more light on the safety and adverse events associated with the biological therapy of CRSwNP. A comprehensive systematic review was conducted on the safety of different biological treatments when used for managing CRSwNP. We have included 13 studies in the present systematic review, including 12 randomized controlled trials (RCTs) and one cross-sectional study. The total sample size for the included studies was 2282 patients. Six studies investigated the safety and adverse events of dupilumab; three investigated omalizumab, three investigated mepolizumab, and only one investigated reslizumab. Some studies have reported that adverse events were common with these types of drugs. However they were not specific and self-limited. Headaches, injection site reactions, and pharyngitis were the most common adverse events found among the reported adverse events. The Dupilumab trial reported pharyngitis in 225 patients (22.4 %) followed by erythema in 9.4 %, headache in 8.1 %, epistaxis in 5.1 %, and asthma in 1.7 % of patients. Trials which used omalizumab reported headaches, nasal pharyngitis, injection-site reactions to be the most common adverse events with estimated prevalence rates of 8.1 %, 5.9 %, and 5.2 %, respectively. Mepolizumab and reslizumab studies reported that 40 % of patients were complicated by nasal polyps/congestion/pharyngitis/infections, 14 had a headache (15.5 %), two developed asthma (2.2 %), and only one patient (1.1 %) had epistaxis as an adverse event. Although the literature's current investigations indicate the safety of the biologic treatment modalities, further studies are needed as some uncertainty among the trials have been reported.

Hemostatic effect of hot saline irrigation during functional endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: The endoscopically magnified operative field in functional endoscopic sinus surgery (FESS) makes even a small amount of bleeding a potentially significant hindrance. It is thought that irrigation with hot saline during surgery may improve surgical field of view by producing a hemostatic effect. Our objective was to assess the effectiveness of hot saline irrigation (HSI) compared to room temperature saline irrigation (RTSI) in the control of intraoperative bleeding during FESS. METHODS: Sixty-two chronic rhinosinusitis (CRS) patients undergoing FESS were randomized to 2 treatment arms in an equal ratio. Subjects received either HSI (49°C) or RTSI (18°C), 20 mL every 10 minutes, for the duration of FESS. The Boezaart endoscopic field of view grading system was the primary outcome measure. Boezaart score, heart rate, and mean arterial blood pressure (MABP) were recorded at 10-minute intervals between irrigations. RESULTS: Mean endoscopic surgical field of view (Boezaart score) did not significantly differ between the HSI and RTSI groups (1.5 ± 0.6 vs 1.3 ± 0.5; p = 0.23). However, when FESS was longer than 2 hours in duration, the Boezaart scores were significantly better in the HSI group (1.6 ± 0.6 vs 1.2 ± 0.4; p = 0.04). We found that blood loss per minute was significantly reduced (p = 0.02) in all cases in which HSI was used (2.3 ± 1.0) compared to RTSI (1.7 ± 1.1). Despite this, heart rate (p = 0.32) and MABP (p = 0.14) did not significantly differ between treatment groups. CONCLUSION: HSI may be beneficial in improving surgical field of view in FESS after 2 hours of operating time. A significant reduction in rate of blood loss may be attained with HSI.

The safety and efficacy of short-term budesonide delivered via mucosal atomization device for chronic rhinosinusitis without nasal polyposis.

BACKGROUND: Budesonide is a potent corticosteroid commonly prescribed for management of inflammation in chronic rhinosinusitis (CRS). The standard for prescribing budesonide is via impregnated nasal saline irrigation (INSI), although recently the mucosal atomization device (MAD) has emerged as a theoretically superior method of distributing medication into the sinuses. The MAD atomizes medication into small droplets and this is thought to enhance absorption and improve bioavailability. However, no studies have shown whether enhanced absorption and improved bioavailability of budesonide via MAD causes adrenal suppression. The objective of this study is to determine whether budesonide via MAD affects the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Twenty CRS patients were recruited from a tertiary rhinology clinic and randomized to take budesonide (1 mg) via MAD or via INSI twice a day for 60 days. The adrenocorticotropic hormone (ACTH) stimulation test and 22-item Sinonasal Outcomes Test (SNOT-22) questionnaire were administered on days 1, 30, and 60 of the study. Plasma budesonide and cortisol levels were simultaneously quantified using a high-performance liquid chromatography-tandem mass spectrometry technique. RESULTS: There was no indication of adrenal suppression in either group (n = 20) based on ACTH stimulation test results nor was there significant plasma budesonide levels detected in either group. Quality of life, as indicated by SNOT-22, did not differ between groups at 60 days (p = 0.404; 95% confidence interval [CI], -37.2 to 15.9), but SNOT-22 scores for patients using MAD did show statistically significant improvement at 60 days compared to baseline (p = 0.02). CONCLUSION: The MAD is likely a safe and effective method of delivering budesonide to the sinuses in the short term.

Addressing animal model issues in auditory research.

OBJECTIVE: To better understand the differences in auditory systems across species. METHODS: Auditory brainstem response (ABR) click thresholds were obtained from normal 3- to 6-week-old animals including 15 guinea pigs, 62 mice, and 6 rats. Pure-tone ABR thresholds were obtained in 7 guinea pigs, 6 mice, and 13 rats. Threshold variability was then considered a function of basilar membrane length, mean body weight, basal metabolic rate, and longevity as identified in the literature. RESULTS: Interspecies variability of auditory thresholds for normal-hearing animals is not explained by differences in mean body weight, metabolic rate, or longevity. Simple linear models appear to adequately describe threshold variability across the parameters studied. Click thresholds, with significant low-frequency content, suggest that mice have better hearing than rats or guinea pigs. CONCLUSION: In spite of wide variations in cochlear anatomy and metabolic factors, different species have evolved similar auditory thresholds across species in normal, young animals.