THE ASSOCIATION BETWEEN AMINOGLYCOSIDE EXPOSURE AND OTOTOXICITY IN CHILDREN WITH CYSTIC FIBROSIS.

INTRODUCTION: Pulmonary exacerbations increase the requirement of aminoglycoside (AG) antibiotics in people with cystic fibrosis (pwCF). Several studies have shown that AGs have a cumulative effect on ototoxicity. We aimed to investigate the relationship between AG exposure and ototoxicity by using three different methods in patients with CF. MATERIALS-METHODS: The multicenter study included 121 pwCF aged between 5-18 years with a history of parenteral AG exposure. Standard pure tone audiometry (sPTA), extended high frequency audiometry (EHF-PTA), and distortion-product otoacoustic emissions (DPOAE) tests were performed. Mitochondrial mutation analysis for m1555G>A was performed in 61 patients. RESULTS: Median age was 12.85 years and 52.1% (n=63) were male. 18.2% (n=22) of the patients had received parenteral AGs more than 5 courses/lifetime. Ototoxicity was detected in at least one of the tests in 56.2% (n= 68) of the patients. Only 10.7 % (n=13) of the patients had reported a symptom indicating ototoxicity. 30.3% (n=30) of the patients had ototoxicity in the low-exposure group while it was 45.5% (n=10) in the high-exposure group according to EHF-PTA (p>0.05). Median number of parenteral amikacin courses was significantly higher in the ototoxic group [2(1.25-5.75) vs 2(1-3); p=0.045]. No m1555A>G mutation was detected in 61 patients who screened for mitochondrial mutation analysis. CONCLUSION: As AG ototoxicity occurs primarily at high frequencies, EHF-PTA is important in early detecting otoxicity. EHF-PTA and DPOAE detected ototoxicity in some patients with normal PTA results. All pwCF with a history of AG exposure should be evaluated for hearing loss since symptoms may only be noticed in the late period.

Unveiling the Respiratory Muscle Strength in Duchenne Muscular Dystrophy: The Impact of Nutrition and Thoracic Deformities, Beyond Spirometry.

BACKGROUND/OBJECTIVES: Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, the predictability of upright-supine spirometry in terms of diaphragm involvement, and the impact of nutrition on muscle strength. METHODS: This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. The effects of the ambulatory status, kyphoscoliosis, chest deformity, and low BMI on respiratory parameters were investigated. RESULTS: Forty-four patients were included in the study. The mean patient age was 10.8 ± 2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and non-ambulatory patients (p < 0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with a low BMI than in those without (p < 0.05). CONCLUSIONS: To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for nutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

Beyond the 10%: Unraveling the genetic diversity in Turkish cystic fibrosis patients not eligible for CFTR modulators.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by variants of CFTR gene. Over 2000 variants have been identified, and new drugs called CFTR modulators have been developed to target specific defects in the CFTR protein. However, these drugs are only suitable for patients with certain variants of CFTR, and eligibility rates vary depending on race and geographical region. This study aimed to reveal the detailed genotype and clinical characteristics of people with CF (pwCF) at our center in Turkey, a developing country, who are not eligible for CFTR modulators. METHODS: A total of 445 pwCF followed up at Marmara University were reviewed retrospectively. Variants of the patients ineligible to CFTR modulators were classified based on American College of Medical Genetics guidelines, CFTR classification, the change in the encoded protein, and the variant type. RESULTS: The study revealed that 139 (31.2%) patients weren't eligible for CFTR modulators. There were 60 different variants in the 276 alleles, as two were missing. The majority of patients had missense or nonsense variants, and that the most common variant was c.1545_1546del, which can be said unique to this geography. CONCLUSION: The study highlights the importance of detecting the variants of ineligible patients in detail to guide future approaches for more targeted and effective interventions in CF care. Testing the effectiveness of CFTR modulators for rare or newly occurring variants is crucial to ensure equal access for pwCF to these therapies from different racial backgrounds and ethnic minorities.