Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease.

PURPOSE: To characterize the frequency, severity, and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED). DESIGN: Prospective observational case series. METHODS: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Laboratory test results were collected at baseline and during treatment. Audiometry, patulous eustachian tube (PET) testing, and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and posttreatment testing. RESULTS: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3 years old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2-week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, whereas only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and posttreatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and 1 patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (P = .008). CONCLUSIONS: Hearing loss is a concerning adverse event of teprotumumab, and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring, and prevention guidelines are needed.

Asthma, FEF25-75, and Hospitalizations in Children.

Asthma is a common chronic pediatric respiratory disease associated with significant morbidity. Current guidelines recommend monitoring forced expiratory volume in 1 s (FEV1) as part of the assessment of asthma severity and control; however, many children with asthma have a normal FEV1 despite significant symptoms. Reduced forced expiratory flow between 25%-75% of forced vital capacity (FEF25-75) may be an important measure of asthma severity and control in children with normal FEV1. This study examines the association between FEF25-75 and asthma-related hospitalizations. Pulmonary function tests and records of 925 children ≤19 years of age seen for an initial evaluation of physician-diagnosed asthma at a community-based asthma clinic between 1999 and 2011 were reviewed. FEV1 ≥80% predicted and FEF25-75 ≥60% were considered normal. The associations between FEV1 and FEF25-75 and asthma-related hospitalizations were examined using logistic regression models. Thirteen percent (n=118) of the children were hospitalized for asthma at least once in the previous year. Fifty four percent (n=501) of the children met criteria for uncontrolled asthma symptoms. Asthma-related hospitalization was associated with reducing categories of FEF25-75, but not FEV1. Among the 693 children with normal FEV1 (≥80%), those with FEF25-75 <60% were more likely to have been hospitalized in the previous year (odds ratio 2.50, confidence interval 1.17-5.35) as compared to those with FEF25-75 ≥60% of predicted. In a diverse urban cohort of children with asthma, asthma-related hospitalization in the previous year was associated with reduced FEF25-75 even among those with normal FEV1. Our results suggest that FEF25-75 may provide important information in the assessment and management of asthma in children.