Dysphagia and Lung Disease in Children With Spinal Muscular Atrophy Treated With Disease-Modifying Agents.

OBJECTIVES: Disease-modifying agents (DMAs) for the treatment of spinal muscular atrophy (SMA) have evolved the SMA phenotype with improved survival. Ongoing oropharyngeal dysphagia and respiratory complications are reported. The extent of dysphagia and respiratory morbidity in this population, since DMAs' introduction, has not been well described. METHODS: A whole-population study involved all children with treated SMA types 1-3 in our facility. Videofluoroscopic swallow studies (type 1 alone), chest CT scans, and clinical data were collected. RESULTS: Thirty-six children were included (n = 9 type 1, n = 14 type 2, and n = 13 type 3; age range 0.3-15.4 years). Abnormal swallowing characteristics were demonstrated in all children with type 1 (n = 8; 100%). Bronchiectasis was found on chest CT: 3 of 9 (33.3%), 2 of 14 (14.3%), and 2 of 13 (15.4%) of type 1, 2, and 3, respectively. Atelectasis, mucus plugging, bronchial wall thickening, and parenchymal changes were common. DISCUSSION: Swallow impairments were universal in children with type 1. Bronchiectasis was common in all pediatric SMA types, with a prevalence of 1 in 5. Routine monitoring and management of dysphagia/recurrent respiratory infection should be implemented for improvement in lung health.

Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3.

INTRODUCTION: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown. AIM: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment. METHODS: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test. RESULTS: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen. CONCLUSION: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

Pleural effusion secondary to chronic pancreatitis in childhood.

Pleural effusion secondary to a pancreatico-pleural fistula is a very rare presentation in children, with limited reports in the literature. We describe two differing presentations of pleural effusions resulting from chronic pancreatitis (CP) with successful resolution of the pleural effusion. These cases highlight the need for consideration of this rare paediatric diagnosis, and the variety of investigations, management strategies, and complications that can occur in the setting of CP in children.

Endobronchial vasculitis in childhood granulomatosis with polyangiitis.

Laryngo-tracheo-bronchial disease in childhood granulomatosis with polyangiitis may acutely present with endobronchial small vessel vasculitis without airway stenosis. Treatment should not be delayed in the presence of haemoptysis as it may indicate acute pulmonary capillaritis which can lead to fatal respiratory failure from diffuse alveolar haemorrhage.

Flexible bronchoscopy in diagnosis and management of dual tracheoesophageal fistula: A case series.

Dual and H-type tracheoesophageal fistulae can present major diagnostic and management difficulties. A methodological approach with flexible bronchoscopy and a guide wire cannulation technique was used to diagnose, localize, and aid operative surgical management in five children with dual and H-type tracheoesophageal fistulae. All children had successful outcomes.

Forced oscillation technique in spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA. METHODS: Children with SMA aged < 10 years were recruited. FOT was performed every 3 months for 12 months (five visits). Spirometry and assisted and unassisted peak cough flow (PCF) were performed where possible. Polysomnography was performed on children with type 2 SMA. Clinical information included SMA type, chest infections, Cobb angle, medications, and mobility. Regression analysis assessed relationships between FOT and FVC, PCF, and apnea/hypopnea index (AHI). Analysis of variance sought relationships to clinical characteristics. RESULTS: Twelve children (seven male) were recruited; mean age was 6.26 (± 2.59) years. Respiratory reactance at 8 Hz (Xrs8) (mean z score, +1.41; SD, 1.90; P < .03) and respiratory resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P < .001) and Rrs8z score worsened (rate of change +0.51, P < .001). No relationship (P > .05) was found between clinical characteristics and FOT values. CONCLUSIONS: FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

Spirometry is affected by intelligence and behavior in Duchenne muscular dystrophy.

Children with Duchenne muscular dystrophy (DMD) have progressive respiratory muscle weakness. Spirometry monitors progress, but is effort-dependent. Intelligence quotients (IQ) average one standard deviation below normal, and behavioral disturbance is common. Our aim was to assess if impaired intelligence or behavior influences spirometry in children with DMD, and if computerized visual incentives (CVI) are beneficial. Forty-seven boys with DMD, of mean age 12.6 years (range, 6-19), were recruited. Full-scale, performance, and verbal IQ, and parent-and-teacher-reported oppositional behavior scores, were recorded. Each was divided into moderate, mild, and no impairment groups. A randomized crossover design was applied to performing spirometry with or without CVI first. A Jaeger Masterscope (version 4.60) was used. Linear regression defined the relationship between spirometry and both IQ and behavior scores. The paired Student's t- test compared spirometry performed with and without CVI for the overall group and subgroups. Boys with DMD can adequately perform spirometry. There is an association between %FEV1 and %FVC with full-scale (r = 0.50, P = 0.002; r = 0.49, P = 0.003, respectively), performance (r = 0.68, P < 0.0005; r = 0.68, P < 0.0005, respectively) and verbal (r = 0.39, P = 0.043; r = 0.36, P = 0.037, respectively) IQ, but not with parent (P = 0.77, P = 0.70, respectively) or teacher (P = 0.90, P = 0.90, respectively)-reported oppositional behavior scores. The effect of CVI was significant in those with moderate full-scale (P = 0.03), performance (P = 0.002), and verbal (P = 0.02) intellectual impairment, and moderately severe teacher-reported oppositional behavior (P = 0.02). In conclusion, spirometry results are related to intelligence in DMD. Using CVI improves the FVC obtained in those with moderate intellectual or behavioral impairment.

Relationship between peak cough flow and spirometry in Duchenne muscular dystrophy.

Spirometry is used to monitor respiratory progress in children with Duchenne muscular dystrophy (DMD). Mucociliary clearance depends on cough strength, which can be measured by peak cough flow (PCF). It is not routinely measured in most centers. When the PCF falls below 270 l/min, mucociliary clearance is likely to be impaired during viral illnesses, and techniques to assist mucociliary clearance should be taught. There is no known association between spirometry and PCF. Our aim was to assess if PCF relates to spirometry measures, and if spirometry can be used to predict when the PCF <270 l/min. Children with DMD aged 6-19 years were recruited. Spirometry was performed with a Jaeger Masterscope with version 4.60 software. PCF was performed with a Wright peak flow meter. Data were collected into an Access '97 database, and statistics were performed with Stata 7.0. The association between PCF and spirometry was defined with linear regression. Logistic regression was used to predict the probability that the PCF would be <270 l/min for any given forced vital capacity (FVC) or forced expired volume in 1 sec (FEV1). The risk ratios for PCF <270 l/min were calculated for the spirometry parameters. PCF is associated with FVC (R2, 0.72) and FEV1 (R2, 0.69). The likelihood of PCF <270 l/min rises when FVC <2.l and FEV1 <2.l/sec. The risk ratio for PCF <270 l/min when FVC <2.1 l is 4.80 (1.72-13.40) and when FEV1 <2.1 l/sec is 3.94 (1.43-10.85). In children with DMD, PCF should be measured when FVC <2.1 l or FEV1 <2.1 l/sec, so that techniques to assist with mucociliary clearance can be effectively used.

Height prediction from ulna length.

Height is fundamental to assessing growth and nutrition, calculating body surface area, and predicting pulmonary function in childhood. Its measurement is hindered by muscle weakness, joint, or spinal deformity. Arm span has been used as a substitute, but is inaccurate. The objective of the study was to identify a limb measurement that precisely and reproducibly predicts height in childhood. Males (n=1144) and females (n=1199), aged 5 years 4 months to 19 years 7 months, without disability were recruited from Melbourne schools. Height, arm span, ulna, forearm, tibia, and lower leg lengths were measured with a Harpenden stadiometer and anthropometer. Prediction equations for height based on ulna length (U) and age in years (A) were developed using linear regression. Ulna centile charts were developed by the LMS method. For males, height (cm)=4.605U+1.308A+28.003 (R2=0.96); for females, height (cm)=4.459U+1.315A+31.485 (R2=0.94). Intra- and inter-observer variability was 0.41% and 0.61% relative to the mean, respectively. Height prediction equations from tibia, forearm, and lower leg length were calculated. We show that ulna measurement is reproducible and precisely predicts height in school-age children. It appears to be superior to arm span measurement when neuromuscular weakness, joint, or spinal deformity exists. Ulna growth charts should facilitate growth assessment.

Prediction of childhood pulmonary function using ulna length.

Pulmonary function is important in neuromuscular weakness. In children, height determines normal values. Height measurement is unreliable when neuromuscular weakness or spinal deformity is present. The aim of this study was to accurately predict pulmonary function from a limb segment measurement that is precise and reproducible. Normal males (n = 1,144) and females (n = 1,199), 5.3 to 19.6 years old, were recruited from Melbourne schools. Height, weight, ulna, forearm, tibia, and lower leg lengths were measured using a Harpenden stadiometer and calipers, and electronic scales. Three maximal expiratory maneuvers were performed. Limb measurements were highly reproducible. Linear regression on log-transformed FEV1 and FVC was used to develop prediction equations from limb measurements and age. In males FEV1 = exp (0.071 x U + 0.046 x A - 1.269), r2 = 0.86; FVC = exp (0.77 x U + 0.041 x A - 1.285), r2 = 0.86 and in females FEV1 = exp (0.072 x U + 0.041 x A - 1.272), r2 = 0.84; FVC = exp (0.078 x U + 0.037 x A - 1.315), r2 = 0.83 (U refers to ulna length and A refers to age). Precision is similar to equations using height. Ulna measurement is accessible in wheelchair-bound children. Using ulna length to predict pulmonary function should facilitate respiratory assessment in children whose height is difficult to measure.