Ok so I'm definitely procrastinating this morning. Instead of doing work, I'm catching up on writing in my blog! :)
Below is what I'm doing this summer at the Cleveland Clinic. I initially contacted this physician because I wanted to start feeling more empowered by my newly diagnosed asthma. By learning absolutely everything I can about asthma, I'm starting to feel better about having asthma.
Use of exhaled breath condensate to monitor nitric oxide metabolites before and after allergen challenge in asthma patients
Natalia M. Grob
Department of Pulmonary, Allergy, and Critical Care Medicine and Pathobiology, Lerner Research Institute and Cleveland Clinic, Cleveland, OH
Asthma affects more than 20 million people (ALA, 2005). Despite continued research and advances in treatment, the incidence of asthma is rising and asthma-related mortality continues to increase at astonishing rates. Asthma is a disease characterized by bronchial hyperresponsiveness, airway obstruction, and inflammation. The exaggerated narrowing of airways that occurs in asthma occurs after inhalation of a myriad of stimuli including common allergens, microbes, and pollution.
Asthma exists as two forms: allergic and non-allergic asthma. In allergic asthmatics, the presence of an allergen stimulates an inflammatory process that leads to airway obstruction. The antigen cross-links to a specific IgE on mast cells present in the bronchial mucosa or submucosa, leading to the degranulation and release of leukotrienes, prostaglandins, and other inflammatory mediators. Together, these mediators stimulate the inflammation and smooth muscle contraction that lead to the air flow obstruction present in asthma.
The presence of these mediators and their end-products can illustrate an augmentation of the inflammatory response and be used to predict lung function. For example, nitric oxide (NO) has been used as a surrogate marker for airway inflammation because of its role in the regulation of smooth muscle tone of pulmonary blood vessels and bronchi as well as a role in the mediation of vasodilation. Khatri, et al. (2001) and other have shown increased NO during asthmatic response following an allergen challenge. Smith, et al. (2005) further demonstrated that exhaled NO measurements could be used to guide treatment in chronic asthma: NO levels increased in proportion to bronchial wall inflammation and airway hyperresponsiveness. NO acts as a free radical and is quickly oxidized to nitrite and nitrate by macrophage activation. By monitoring NO, Smith, et al. (2005) demonstrated the potential for using mediators to assess and predict lung function.
Although NO levels have been useful in predicting airway inflammation in asthma, exhaled NO levels in the gas phase may not tell the complete story. NO levels in the exhaled gas at any point in time are the result of a complex biology and biochemistry in the airway that is dependent on the other substances in the airway milieu. NO quickly reacts with oxygen, superoxide, water, thiols, amides, and lipids to produce several endproducts of NO metabolism with varying and sometimes opposing biological effects. Thus, NO levels in the gas phase in the asthmatic airway need to be interpreted in the context of other products of NO metabolism. Monitoring these metabolites in exhaled breath may offer a method to evaluate perturbances in airway chemistry before this is reflected in exhaled NO levels. This has been clearly demonstrated by measuring NO metabolite levels in bronchoalveolar lavage specimens (Dweik et al., 2001). The bronchioalveolar lavage procedure, however, is an invasive method which limits its usefulness to the research setting. For NO metabolite measurement to be clinically useful, a non-invasive method is needed to collect lower airway lining fluid to measure these metabolites. One such method that has become available in the past few years is exhaled breath condensate (EBC) (Horvath et al., 2005). Exhaling through a cooling system generates EBC. The condensate contains the metabolites present in the exhaled tidal breath, including mediators of the NO pathway including markers of inflammation and oxidative stress released from an asthmatic lung (Liu & Thomas, 2005). This procedure is a non-invasive and safe with substantially reduced risk for influencing airway function or inflammation in contrast to bronchoalveolar lavage (Liu & Thomas, 2005).
This summer, I plan on using EBC to monitor levels of NO metabolites and how they change after an allergen challenge (which induces a mild controlled asthma attack) in patients with asthma. Our hypothesis is that in addition to exhaled NO levels, NO metabolites in exhaled breath condensate can provide a better and more accurate method to predict the occurrence of an asthma attack and its resolution. Collection of EBC will be preformed immediately before and after the challenge while still in the clinic. Specimens will also be collected at 8, 24, and 48 hours after the challenge. The non-invasive nature of this procedure allows for the repeated collection without a significant risk to research participants. This project will be performed as part of a much larger NIH-funded Program Project studying the pathobiology of asthma. The subjects of this study will be categorized into four groups: allergic asthma, non-allergic asthma, allergic without asthma, and non-allergic without asthma. Atopy will be detected by skin test reactivity to a panel of common environmental allergens, as described in Khatri, et al. (2001). Other specimens to be collected on the same individuals in the project include exhaled breath, blood, and urine. All individuals will also have pulmonary function tests. My role in the project will be to collect the exhaled breath condensate samples and help run the NO metabolites assay.
Reference:
American Lung Association. Epidemiology & statistics Unit, Research and Program Services. Trends in Asthma Morbidity and Mortality May 2005.
Dweik, R.A., Comhair, S.A., Gaston, B., Thunnissen, F.B.J.M., Farver, C., Thomassen, M.J., Kavuru, M., Hammel, J., Abu-Soud, H.M., & S.C. Erzurum (2001). NO chemical events in the human airway immediate and late antigen-induced asthmatic response. Proceedings of the National Academy of Sciences of the United States of America, 98(5): 2633-2627.
Horvath, I., Hunt, J., Barnes, P.J., Alving, K., Antczak, A., Baraldi, E., Becher, G., van Beurden, W.J., Corradi, M., Dekhijzen, R., Dweik, R.A., Dwyer, T., Effros, R., Erzurum, S., Gaston, B., Gessner, C., Greening, A., Ho, L.P., Hohlfeld, J., Jobsis, Q., Laskowski, D., Loukides, S., Marlin, D., Montuschi, P., Olin, A.C., Redington, A.E., Reinhold, P., van Rensen, E.L., Rubinstein, I., Silkoff, P., Toren, K., Vass, G., Vogelberg, C., Wirtz, H., & ATS/ERS Task Force on Exhaled Breath Condensate (2005). Exhaled breath condensate: methodological recommendations and unresolved questions. European Respiratory Journal, 26(3): 523-548.
Khatri, S.B., Ozkan, M., McCarthy, K., Laskowski, D., Hammel, J., Dweik, R.A., & S.C Erzurum (2001). Alterations in exhaled gas profile during allergen-induced asthmatic response. American Journal of Respiratory and Critical Care Medicine, 164: 1844-1848.
Liu, J. & P.S. Thomas (2005). Exhaled breath condensate as a method of sampling airway nitric oxide and other markers of inflammation. Medical Science Monitor, 11(8): MT53-62.
Smith, A.D., Cowan, J.O., Brasset, K.P., Herbison, G.P., & D.R. Taylor (2005). Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. The New England Journal of Medicine, 352(21): 2163-2174.
