Richard Taylor started work-ing in Professor George’s lab in Spring, 2008, which he describes as the opportunity to work “on an innovative approach to diagnosing asth-ma, on a team bringing their unique talents and experiences together to solve a common problem.” He found it particu-larly rewarding to be able to contribute practical results to a problem that is so widespread and poorly understood. Upon graduating from UCI, Richard hopes to make a career of research, pursuing a Ph.D., and eventually working and teach-ing at a research institution.Exhaled nitric oxide (eNO) is elevated in asthmatics and is a pur-ported marker of airway inflammation. By measuring eNO at mul-tiple flows and applying models of eNO exchange dynamics, the signal can be partitioned into its proximal airway [J’awNO (nl/s)] and distal airway/alveolar contributions [CANO (ppb)]. Several studies have demonstrated the potential significance of such an approach in children with asthma. However, techniques to parti-tion eNO are variable, limiting comparisons among studies. This project demonstrates that when using the multiple flow technique to partition eNO, the method of analysis (constant time versus constant volume interval) significantly affects the estimation of CANO, and thus potentially the assessment and interpreta-tion of distal lung inflammation.Key TermsAsthmaMulti-Compartment ModelNitric OxidePulmonary InflammationSampling IntervalDetermining the Optimal Sampling Interval of the Exhaled Nitric Oxide ProfileRichard W. TaylorBiomedical EngineeringSteven C. GeorgeHenry Samueli School of EngineeringNitric oxide (NO) is present in exhaled breath after being produced by cells throughout the lungs. NO is affiliated with inflammation, including pulmonary inflammatory diseases such as asthma. The widespread and growing presence of asthma highlights the need for improved diagnosis and treatment methodologies; the affiliation between NO and inflammation gives rise to the possibility that NO measurements could be used as a clinical tool in the diagnosis and treatment of inflammatory pulmonary disease. As one step toward this goal, this study sought to discover the most reliable interval of the exhaled NO signal for analysis. Exhaled NO measurements of 51 patients aged 7–16 years with mild to moderate asthma were collected at the Breathmobile operated by the Children’s Hospital of Orange County. Exhaled volume was measured relative to each subject’s airway volume and collected at flows of 50, 100, and 200 ml/s. The volume of exhaled breath was normalized relative to the volume of the airway tree. The data shows that the clearest and most reliable interval of the exhaled breath on which to measure nitric oxide is from four to six airway volumes. This information will enable more reliable use of exhaled nitric oxide, ultimately enabling more accurate asthma diagnosis and treatment decisions for the pediatric population.69 T HE UCI UNDERGRADUATE RESEARCH JOURNALAuthorAbstractFaculty Mentor70 The UCI Undergraduate Research Journal DETERMINING THE OPTIMAL SAMPLING INTERVAL OF THE EXHALED NITRIC OXIDE PROFILEIntroduction and BackgroundThe Problem: AsthmaAsthma is a pulmonary inflammatory disease characterized by episodes of bronchocontriction and airway hyperrespon-siveness (Puckett, 2008). Left untreated, asthma can result in airway wall remodeling and ultimately in fixed airflow obstruction. Clinical symptoms include wheezing, dyspnea, chest tightness, and cough, and are triggered primarily by exercise, emotional distress, allergies, air pollutants, and viral infection (Kumar, 2005). At its worst, asthma can culminate in Status Asthmaticus, an attack lasting days to weeks and possibly resulting in death. Also, asthma-induced inflamma-tion is normally treated with inhaled corticosteroids, which have significant problematic side effects, and bronchodila-tors such as a β2 agonist. Current diagnostic methods are limited to spirometry and symptom analysis; these can be particularly limiting in young children, who may have trouble performing spirometry or describing symptoms. Furthermore, spirometry can be normal in asthmatic chil-dren. These methods are particularly unacceptable given the scope of asthma: approximately 20 million Americans suffer from asthma; worldwide, the number of people with asthma is growing, particularly in industrial nations that produce asthma-triggering air-pollutants (Beasley, 2004). Symptoms and spirometry, meanwhile, do not correlate well with airway inflammation (Lious, 2000, Wilson, 2000, and van dem Toom, 2001). This is a problem because patients can subsequently receive under- or over-treatment. Therefore, treatment decisions can be improved by devel-oping a diagnosis that overcomes these shortcomings and is based upon a more reliable marker of inflammation.A Potential Tool: Nitric OxideNitric oxide (NO) is a mediator of pulmonary inflamma-tory processes (Kobzik, 1993). Nitric oxide synthase (NOS) produces NO throughout the pulmonary system by the oxi-dative conversation of L-arginase. There are three known NOS isoforms, which are expressed in the airway epithelial cells and the bronchial and alveolar epithelium. NO func-tions as an endogenous messenger in the lungs, influencing such systems as smooth muscle tone, ciliary function, and, most relevant to this research project, acting as a natural bronchodilator (Moncada, 1991). NO therefore increases as inflammation increases (e.g. during asthma) and decreases when the inflammation decreases. Therefore, the ability to measure and characterize quantity, location, and rate of NO production throughout the pulmonary system may be an effective tool in asthma diagnosis, which may improve treatment decisions and enable an earlier, more accurate diagnosis, particularly in children.ComplicationsExhaled NO was first detected in 1991 (Gustaffson, 1991). Early studies noted an association between asthma and exhaled NO levels, concluding that NO could be used as an indicator of inflammation (Kharitonov, 1994). More recent investigations, two on adults and two on children, attempted appropriate corticosteroid delivery based on exhaled nitric oxide, but perceived only marginal benefits in adults and none in children (Petsky 2008). Still more studies questioned the utility of exhaled NO for asthma diagnosis, concluding that measurements of elevated NO could not be used to distinguish between asthmatic
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