Introduction/Aims Spinal muscular atrophy (SMA) type III is a relatively mild form of SMA. Few studies have investigated the changes in both respiratory and upper limb function within this population after loss of ambulation. The aim of this study was to assess change in percentage of predicted forced vital capacity (FVC% predicted) and change in the Revised Upper Limb Module (RULM) score in these patients throughout a 24‐month period after loss of ambulation. Effect of scoliosis and its surgical correction, disease duration since loss of ambulation, weight, and height were also investigated. Methods Retrospective analyses were performed on 24 nonambulant SMA III patients from data collected at two centers in the United Kingdom. Results The FVC% predicted score showed a significant progressive deterioration of 17% over the 24‐month period. Respiratory deterioration correlated significantly with age, weight, disease duration since loss of ambulation, and spinal correctional surgery. Longitudinal RULM data were available for 16 patients; a significant deterioration was observed with a mean decrease in score of 3 over 24 months. Age correlated negatively with RULM score, as did height and time since loss of ambulation. A significant positive correlation between FVC% predicted and RULM was demonstrated. Discussion This study highlights how SMA type III patients have progressive deterioration of respiratory and upper limb function after loss of ambulation. Combining data from these assessments could provide insight into clinical progression, inform clinical trials, and provide assistance in managing disease progression expectations for patients.
Objectives Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly diverse range of diseases. Several recently identified genes highlight the overlap between peripheral neuropathies and congenital myasthenic syndromes (CMS). The beta-2 adrenergic receptor agonist salbutamol has been shown to provide symptomatic benefit in CMS, while improving structural defects at the NMJ. Based on these findings, we identified cases of motor neuropathy with NMJ dysfunction and assessed the effect of salbutamol on motor function. Methods Cases of motor neuropathy with significant NMJ dysfunction, were identified using repetitive nerve stimulation and single fibre electromyography. Oral salbutamol was administered for 12 months. Repeat neurophysiological and clinical assessments were undertaken at baseline, 6 months and 12 months. Results Significant defects of neuromuscular transmission were identified in 15 patients harbouring a range of genetic defects, including mutations in GARS1, DNM2, SYT2 and DYNC1H. No clear benefit on motor function was seen following the administration of 12 months of oral salbutamol; however, there was a significant improvement in patient reported fatigue. In addition, no clear effect on neurophysiological parameters was seen in patients treated with salbutamol. Side-effects due to off-target beta-adrenergic effects were significant in the patient cohort. Conclusion These results highlight the involvement of the NMJ in several subtypes of motor neuropathies, including subtypes of neuropathy due to deficits in mitochondrial fusion-fission, synaptic vesicle transport, calcium channels and tRNA synthetases. Whether the NMJ dysfunction is simply due to muscle reinnervation or a pathology unrelated to denervation is unknown. The involvement of the NMJ may represent a novel therapeutic target in these conditions. However, treatment regimens will need to be more targeted for patients with primary inherited defects of neuromuscular transmission.
Results 192 prescriptions corresponding to 112 patients were identified. 62 of 112 (56%) were prescribed long-term azithromycin. Bronchiectasis (60%), COPD(19%), asthma (8%), ILD (7%), Bronchiolitis and others (6%) were the variety of diseases for which Azithromycin was prescribed. 28% had pseudomonas colonisation.51(46%) patients were prescribed long-term azithromycin. Of these, 21 (25%) had been on azithromycin for less than 12 months.Sixty eight (82%) patients on long-term azithromycin had had LFTs and 3(3.5%) had audiology testing in the preceding 12 months.21(25%)had documented ECGs with Qtc interval.No patients tested had hearing loss and no documented QTc prolongation.The other common side effect noticed was GI upset in 6 patients (5.6%).The dosing was mostly 250mg three times a week 103(92%) There was also 500mg three times a week in 20(18%) H.influenzae (42%)Staphylococcus aureus (21%)Moraxella catarrhalis (11%)coliform sp (10%). We identified no new NTM in our Cohort. Conclusion Although formal monitoring in this cohort was patchy, Significant documented adverse effects in this cohort were rare and optimal practice for long-term management of azithromycin use remains to be established. Introduction and Objectives Non CF Bronchiectasis has diverse aetiologies. This includes idiopathic, systemic disease related and as a complication of asthma. Such diversity may be important in determining therapeutic strategies (personalised medicines) and may also be an important consideration in clinical trial design. This is increasingly relevant when neutrophil targeting or eosinophil targeted therapies are being developed. We hypothesised that patients could be phenotyped by sputum cytospins irrespective of suspected aetiology or disease severity. Methods Patients underwent a standardised clinical phenotyping protocol including HRCT chest (Anwar et al 2013). Baseline therapy was recorded. Spontaneous sputa were collected in stable state and spirometry was undertaken according to guidelines. Sputum cell counts were calculated using standard methods with data expressed as medians and ranges. P112 DEEPER PHENOTYPING OF NON CF BRONCHIECTASIS THROUGH SPUTUM DIFFERENTIAL COUNTSResults Fifty three patients' data are reported. The M:F ratio was 1:1.4. The mean FEV1 predicted was 62%, mean FEV1/VC ratio was 64%. Forty three (83%) were on inhaled corticosteroids and 24.5% had a historical diagnosis of asthma and /or ABPA. The predominant cell in sputa was neutrophils, median 94 (range 23-100%), macrophages were the 2nd most prevalent cell type median 2.6 (range 0-75%). Eosinophils showed a skewed distribution with median of 0.2 with a range of 0-24.8%. Four patients had sputum eosinophilia >3%. Of these, only 2 had a history of asthma and / or ABPA being diagnosed. Despite historical diagnoses of asthma and / or ABPA in 13 patients the eosinophil percentage was not statistically different to "non asthmatics". (P = 0.59 Chi Sq test) This group included features of ABPA in 2 patients and significant atopy in another.
Results We were able to define 4 discrete clusters of patients based on 9 routinely collected clinical variables using data from 537 patients and 12200 encounters. Lung function outcomes were not used to define the clusters, however, there was a distinction between the different clusters, such that the cluster with the poorest outcomes also had the worst lung function. The cluster with the poorest outcomes also had the greatest risk of hospitalization and pulmonary exacerbation, which suggests that the approach correctly identifies patients with a more severe disease phenotype. The results were consistent in the GOSH clinical data. Conclusion Four clusters of pediatric CF patients were identified with corresponding differences in clinical characteristics and outcomes. Future work will identify risk factors for transitioning to a severe disease cluster, and those factors that may improve health outcomes.
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