Respiratory effects of nusinersen in Spinal Muscular Atrophy (SMA) are largely unknown. Aim: To assess change in respiratory function in pediatric SMA in year 1 of nusinersen treatment & compare to pre-treatment decline rate. Methods: 12-month prospective study of all childhood SMA type 1-3 in Queensland, Australia from 2018. Peripheral muscle strength tests performed prior to & 4 occassions during study with age appropriate respiratory tests attained each visit. Full diagnostic Polysomnography conducted initially & study completion. Lung function 2 years prior to study collected retrospectively. Rates of lung function decline compared prior to & following comencement of nusinersen. Comparisons made between PSG pre & post 12 months treatment. Muscle strength responders & non-responders compared for respiratory parameter change. 31 children included (18 males, 0.25-18.8 years old), 19% SMA type 1, 52% type 2 & 29% type 3. Annual rate decline of Forced Vital Capacity (FVC) z-score reduced for SMA type 2 (p=0.009) and type 3 SMA (p=0.3). Mean total apnoea-hypopnoea index reduced in type 1 [12.3 events/hour to 3.7], type 2 [4.5 (SD 3.0 95% CI 1.8-7.3) to 2.9 (SD 3.0 CI 0.1-5.6) p=0.1] and type 3 [5.3 (SD 2.2 95% CI0.14-10.8) to 2.5 (SD 19.98 95%CI 4.34) p=0.4]. No change in FVC z-score between responders and non-responders was noted (FVC z-score 0.5 p=0.5 95%CI -1.2-2.1 r<0.001 and 0.1 p=0.9 95%CI -2.4-2.6 r=0.01 respectively). Conclusion: Nusinersen stabilises lung function, halts progressive decline seen before treatment in type 2 and 3 SMA. Lung function stability seen even in those without peripheral muscle strength response. Improvements in sleep disordered breathing seen in type 1-3.

Background/Aim: Phthalates are ubiquitous in the environment and are found in many household products. Phthalate exposures may increase oxidative stress in individuals via the formation of reactive oxygen species (ROS), potentially affecting respiratory outcomes, with children a vulnerable group. The aim of this study was to investigate the relationship between urinary measures of oxidative stress and urinary phthalate metabolites in school aged children and the identification of any activities or products that may increase measured exposure. Methods: A spot urine sample was collected from children aged between 5 and 12, who lived on the outskirts of an industrial area and who were participating in a respiratory health study. Urinary phthalate metabolites were analysed using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) and 8-hydroxy-deoxyguanosine (8-OHdG) was measured using the Check ELISA method. All samples were adjusted for specific gravity measured using a hand held refractometer. Questionnaire information provided by parents was examined to determine potential sources of phthalate exposure. Results: Median and range of specific gravity adjusted urinary phthalate metabolite concentrations (µg/L) were MMP (4.7, 0.7-180); MCPP (6.20, <0.50-180); MEP (41.0, 2.20-4700); MiBP (39.0, 3.30-1500); MBP (43.0,3.00-1200); MEHHP (47.5, 3.20-670); MECPP (61.0, 3.30-900); MEOHP (31.5, 1.70-610); MBzP (11.0, 0.50 – 300) and MEHP (6.90, 0.60-140). MCHP, MOP, MNP, and MiDP were below the limit of detection. Spearman correlation coefficients for all metabolites were significantly correlated with 8-OHdG with the largest coefficients observed for MBP and MBzP (rs =0.305). The presence of new carpet was associated with increased urinary MEP concentrations while MiBP was increased in those reporting the presence of bedroom and playroom carpet. Conclusions: Phthalate metabolites were commonly detected, albeit at concentrations lower than in many other studies, and were associated with a urinary marker of oxidative stress, showing that even low level phthalate exposure may elicit oxidative stress responses in children.

Vitamin D has entered the spotlight in the search for preventive treatments against asthma and allergic disease due to its immune-modulating functions, shown in experimental models to include promotion of immune tolerance and boosting protection against infection. Vitamin D inadequacy is common, but disparate findings from cohort studies have had a polarising effect on the scientific community regarding the wisdom of advocating vitamin D supplementation for protection against asthma and allergic disorders. We have previously found that in the high-risk Western Australian CAS cohort (selected due to positive parental atopic history), the combination of multiple severe lower respiratory infections and sensitisation to inhaled allergens by age 2 profoundly increased risk of asthma development by age 5. To determine whether vitamin D levels between birth and age 10 years in the CAS cohort are related to frequency of severe respiratory infections in early childhood, allergic sensitisation, and development of asthma by age 5 or 10 years. We used UPLC/MS/MS (accuracy confirmed with DEQAS standards) to measure 25(OH)-vitamin D3, 3-epi-25(OH)-vitamin D3 and 25(OH)-vitamin D2 from cryobanked plasma samples collected from CAS participants at birth, then at 6 months and 1, 2, 3, 4, 5 and 10 years. CAS participants were visited by the study physician up to age 5 years for every episode of respiratory infection. Vitamin D3 inadequacy was common amongst cohort participants, and as expected was highest amongst participants from whom blood was collected in winter; deseasonalised vitamin D3 was calculated for longitudinal comparisons. In all assessments between 6 months (n=233) and 4 years of age (n=189) the majority of participants had inadequate vitamin D3; 51%-67% of participants had insufficient vitamin D3 (50-75 nmol/L) while 18%-28% were vitamin D3 deficient (<50 nmol/L). Analyses addressing the aims are underway and will be presented at the Meeting.