Pulmonary Biomarkers of Inflammation in Chronic Tetraplegia


Principal Investigator: Miroslav Radulovic
Abstract: Persons with tetraplegia exhibit pulmonary dysfunction attributed to paralysis of respiratory muscles leading to inadequate ventilation and inability to clear secretions, predisposing this population to be more susceptible to repeated pulmonary infections. In addition to restrictive pulmonary dysfunction observed, individuals with high cervical lesion often exhibit obstructive respiratory physiology similar to that seen in asthmatics and believed to be due to unopposed parasympathetic innervation to the airways and, possibly, the loss of sympathetic innervation to the lungs. Underlying airway inflammation is the major pathophysiological mechanism in individuals with asthma. Similarly, airway inflammation may play a role in the obstructive physiology observed in individuals with tetraplegia. Our preliminary data from project entitled "The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons with Tetraplegia" (RCDA #B4162C-Radulovic) has demonstrated that individuals with chronic stable tetraplegia have increased levels of fractional exhaled nitric oxide (FeNO) comparable to levels in mild asthmatic subjects, suggesting the presence of underlying airway inflammation. Measurement of more specific biomarkers of airway inflammation that are found in exhaled breath condensates (EBC) will enable better definition of the presence of and, potentially, address contributing factors leading to underlying airway inflammation in the respiratory tract of individuals with chronic tetraplegia. Thus, in turn, can result in development of new therapeutic strategies, such as use of inhaled steroids in this population, and potentially decrease the rate of respiratory complications, decreasing the number of re-hospitalizations and improving the quality of life of affected individuals. The purpose of this study is to determine the presence/absence of exhaled biomarkers of inflammation in individuals with chronic stable tetraplegia and their relationship with FeNO and overall pulmonary function. Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons with chronic cervical SCI may identify treatment options, such as use of inhaled steroids. This approach would be expected to ultimately improve quality of life in affected individuals, decreasing the rate of re-hospitalizations due to respiratory complications and the socioeconomic burden placed on these with SCI and the health care system. PUBLIC HEALTH RELEVANCE: Relevance of the Proposed Work to the VA Patient Care Mission. The Mission of the Department of Veterans Affairs is to provide optimal clinical care for all patients. Compared with able-bodied veterans, persons with SCI require specialized care directly related to the degree of neurologic impairment. It is important to recognize and address the secondary complications of paralysis to improve the longevity and quality of life of persons with SCI. This study may facilitate the development of new cost effective therapeutic approaches for the treatment and prevention of respiratory complications. Significant system- wide cost-savings may result from improvements in our approach to veterans with higher cord lesions. Increasing our understanding of the underlying mechanisms of obstructive respiratory dysfunction observed in individuals with chronic cervical SCI is of utmost importance for guiding future clinical interventions. The finding of underlying inflammation would suggest therapeutic use of specific anti-inflammatory agents. Failing to find markers of inflammation would, in turn, suggest neurological impairment and raise the possibility of alternative treatments, such as inhaled L-NAME. Reduction of underlying airway inflammation in persons with chronic tetraplegia would be expected to reduce the mortality and morbidity associated with respiratory complications, which are the leading cause of mortality during the acute phase of SCI and third leading cause of re-hospitalization in persons with chronic cervical SCI. Apart from decreasing respiratory complications, improvement of overall respiratory function would be expected to increase the quality of life, with potential implications on employability, personal activities, and exercise training. Advances in pulmonary care would be expected to translate into more productive, active and independent lifestyles for affected individuals. Decreasing the rates of hospitalization for individuals with chronic cervical SCI would significantly decrease the financial burden of providing care.
Funding Period: 2009-07-01 - 2010-06-30
more information: NIH RePORT