Assessing airway clearance dysfunction in Friedreich's ataxia: A focus on peak cough flow

BackgroundFriedreich's ataxia (FRDA), a common hereditary ataxia with multisystem involvement, is caused by a biallelic GAA trinucleotide repeat expansion in the FXN gene, leading to reduced frataxin, mitochondrial dysfunction, and oxidative stress. This study evaluates cough effectiveness through voluntary peak cough flow (PCF).ObjectivesThe objective was to assess airway clearance dysfunction in individuals with FRDA by examining PCF and its relationship with pulmonary and oral strength, disease severity, and genetic factors.MethodsThis cross-sectional study, part of the Biomarkers in Friedreich's Ataxia observational study, involved 51 participants with molecularly proven FRDA undergoing respiratory testing, including spirometry, PCF, maximal respiratory pressures, sniff nasal inspiratory pressure, and lingual strength. Neurological impairment was assessed using the Modified Friedreich's Ataxia Rating Scale (mFARS) and Functional Staging for Ataxia.ResultsForty-seven participants completed PCF tests (31 female; mean age 22.60 years). Twenty-nine (61.7%) remained ambulant (mean mFARS 49.91). Seventeen (36.17%) had reduced PCF (<270 L/min). Lower PCF correlated with younger age, earlier disease onset, and decreased respiratory muscle strength. PCF showed strong associations with maximal inspiratory pressure (MIP), forced vital capacity (FVCpp), and maximal expiratory pressure (MEP). Multiple regression identified MIP and age of symptom onset as primary predictors.ConclusionsThe study demonstrates respiratory dysfunction in patients with FRDA, and shows that disease severity and muscle weakness affect airway clearance. PCF is a more direct and clinically meaningful indicator of cough effectiveness than FVCpp. Comprehensive respiratory evaluations, including muscle-strength testing, can identify individuals who may benefit from targeted interventions to prevent complications.