Progressive respiratory muscle weakness and ineffective cough contributes to morbidity and mortality in children with neuromuscular disorders (NMD). Inspiratory muscle training (IMT) aims to preserve or improve respiratory muscle strength and reduce respiratory morbidity. This study intended to determine the safety and efficacy of IMT in children with NMD. A randomized cross-over study compared three-month intervention (IMT) with control periods (no IMT). Children diagnosed with NMD (5-18 years) performed 30 breaths (at 30% of inspiratory muscle strength (Pimax)) with an electronic threshold device, twice daily. During the control period participants did not perform any IMT. Twenty-three children (median (IQR) age of 12.33 (10.03-14.17) years), mostly male (n=20) and non-ambulant (n=14) participated. No adverse events related to IMT were reported. No difference in median patient hospitalization and respiratory tract infection rates between control and intervention periods (p=0.60; p=0.21) was found. During IMT, Pimax and peak cough flow improved with a mean (SD) of 14.57 (±15.67) cmH 2O and 32.27 (±36.60) L/min, compared to 3.04(±11.93)cmH 2O (p=0.01) and -16.59 (±48.29) L/min (p = 0.0005) during the control period. Spirometry, functional ability and total health-related quality of life scores following intervention did not show a significant change. Patient satisfaction with IMT was high (median 8/10 (IQR 5-10)) and adherence was good. A three-month IMT programme in children with NMD appears safe and well-tolerated, with significant improvement in respiratory muscle strength and cough efficacy. The use of IMT could be considered as an adjunct to respiratory management in children with NMD.

Introduction: Temporal trends in CF survival from low-middle-income settings are poorly reported. We describe changes in CF survival after diagnosis over 40 years from a South African (SA) CF center. Methods: An observational cohort study of people diagnosed with CF from 1974 to 2019. Changes in age-specific mortality rates from the year 2000 (versus before 2000) were estimated using multivariable Poisson regression. Data were stratified by current age < or ≥ 10 years and models controlled for diagnosis age, sex, ethnicity, genotype, and P. aeruginosa (PA) infection. A second analysis explored association of mortality with weight and FEV1z-scores at age 5-8 years. Results: 288 people (52% male; 57% Caucasian; 44% p.Phe508del homozygous) were included (median diagnosis age 0.5 years: Q1,Q3: 0.2, 2.5); 58 (35%) died and 30 (10%) lost to follow-up. Among age >10 years, age-specific mortality from year 2000 was significantly lower (adjusted hazard ratio aHR: 0.14; 95% CI: 0.06,0.29; p<0.001), but not among age <10 years (aHR: 0.67; 95% CI: 0.28,1.64; p=0.383). In children <10 years, Caucasian ethnicity was associated with lower mortality (aHR 0.17; 95% CI 0.05,0.63), and time since first PA infection with higher mortality (aHR 1.31; 95% CI 1.01,1.68). Mortality was 7-fold higher if FEV1z was < -2.0 at age 5-8 years (aHR 7.64; 95% CI 2.58,22.59). Conclusion: Overall, CF survival has significantly improved in SA from year 2000 in people older than 10 years. However, increased risk of mortality persists in young non-Caucasian children, and with FEV1z<-2.0 at age 5-8 years.