Asthma; England; Pediatrics; Respiration Disorders; Respiratory Muscles
Our research interests have focused on trying to understand the role of respiratory muscle fatigue in the development of respiratory failure in children. In particular, studying sites along the neuromuscular axis that could potentially fail and lead to impaired performance of the respiratory muscles. Examples of these include phrenic neural activation, neuromuscular transmission and utilization of energy substrate by the muscle. We have determined that neuromuscular transmission failure plays an important in the development of muscle fatigue in the newborn diaphragm, and that this relates to impaired release of neurotransmitter from the nerve terminals. Because of the important role of calcium in neurotransmitter release, we are focusing on the differences between presynaptic calcium channels subtypes in newborn and mature neuromuscular junction.
A second research interest has been childhood asthma. We currently have 2 areas that are being developed in the laboratory. One is to try to understand the mechanisms underlying the development of chronic asthma in childhood, and in particular how airway inflammation might modulate airway smooth muscle function. We will be examining the effect of chronic exposure to several cytokines on ion channel activity in airway smooth muscle, and how this affects the contractile properties of the muscle. We are also interested in performing clinical studies to determine whether the increase in exhaled nitric oxide (NO) that is observed in children with asthma is secondary to increased production or decreased absorption of NO in the lungs. This has implications on understanding the pathogenesis of the inflammatory process in asthma.
Specialized Terms: Respiratory Muscle Fatigue in Children; Development of Chronic Asthma in Children; Pathogenesis of Inflammatory Process in Asthma
- Pashankar FD, Carbonella J, Bazzy-Assad A, Friedman A. Longituindal Follow-Up of Elevated Pulmonary ARtery Pressures in Children with Sickle Cell Disease. Br. J. Haematol, 2008. Dec 1. [Epub ahead of print]. Mar; 144(5):736-41, 2009.
- Nakra N, Bhargava S, Dzuira J, Caprio S, Bazzy-Asaad A. Sleep-disordered breathing in children with metabolic syndrome: the role of leptin and sympathetic nervous system activity and the effect of continuous positive airway pressure. Pediatrics. 2008 Sep;122(3):e634-42.
- Kevill KA, Bhandari V, Kettunen M, Leng L, Fan J, Mizue Y, Dzuira JD, Reyes-Mugica M, McDonald CL, Baugh JA, O'Connor CL, Aghai ZH, Donnelly SC, Bazzy-Asaad A, Bucala RJ. A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome. J Immunol. 2008 Jan 1;180(1):601-8
- Kass, L.J., Bazzy, A.R. Chronic hypoxia delays maturation of neuromuscular transmission in the diaphragm. J Appl Physiol 90:2325-2329, 2001.
- Akiyama Y, Garcia RE, Bazzy AR. Effect of inspiratory training on mitochondrial DNA and cytochrome c oxidase expression in the diaphragm. Am J Physiol, 271: L320-L325, 1996.
- Bazzy, AR, Donnelly, DF, Failure to generate action potentials in newborn diaphragms following nerve stimulation, Brain Research, 600, 349-52, 1993