Protocol for CLASSIC PBB: comparison of lower airway sampling strategies in children with protracted bacterial bronchitis.

BACKGROUND: Protracted bacterial bronchitis (PBB) is an endobronchial infection and a the most common cause of chronic wet cough in young children. It is treated with antibiotics, which can only be targeted if the causative organism is known. As most affected children do not expectorate sputum, lower airway samples can only be obtained by bronchoalveolar lavage (BAL) samples taken during flexible bronchoscopy (FB-BAL). This is invasive and is therefore reserved for children with severe or relapsing cases. Most children with PBB are treated empirically with broad spectrum antibiotics. CLASSIC PBB will compare the pathogen yield from two less invasive strategies with that from FB-BAL to see if they are comparable. METHODS: 131 children with PBB from four UK centres referred FB-BAL will be recruited. When attending for FB-BAL, they will have a cough swab and an induced sputum sample obtained. The primary outcome will be the discordance of the pathogen yield from the cough swab and the induced sputum when compared with FB-BAL. Secondary outcomes will be the sensitivity of each sampling strategy, the success rate of the induced sputum in producing a usable sample and the tolerability of each of the three sampling strategies. DISCUSSION: If either or both of the two less invasive airway sampling strategies are shown to be a useful alternative to FB-BAL, this will lead to more children with PBB having lower airway samples enabling targeted antibiotic prescribing. It would also reduce the need for FB, which is known to be burdensome for children and their families. TRIAL REGISTRATION NUMBER: ISRCTN79883982.

Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA).

Unravelling the complex molecular pathways responsible for motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) remains a persistent challenge. Interest is growing in the potential molecular similarities between these two diseases, with the hope of better understanding disease pathology for the guidance of therapeutic development. The aim of this study was to conduct a comparative analysis of published proteomic studies of ALS and SMA, seeking commonly dysregulated molecules to be prioritized as future therapeutic targets. Fifteen proteins were found to be differentially expressed in two or more proteomic studies of both ALS and SMA, and bioinformatics analysis identified over-representation of proteins known to associate in vesicles and molecular pathways, including metabolism of proteins and vesicle-mediated transport-both of which converge on endoplasmic reticulum (ER)-Golgi trafficking processes. Calreticulin, a calcium-binding chaperone found in the ER, was associated with both pathways and we independently confirm that its expression was decreased in spinal cords from SMA and increased in spinal cords from ALS mice. Together, these findings offer significant insights into potential common targets that may help to guide the development of new therapies for both diseases.