FeNO B Y L E S L I E K U M P F, R R T, C P F T, A E - C
LESLIE KUMPF RRT, CPFT, AE-C Graduated from Henry Ford with a degree in Respiratory Therapy in 2006 Currently working on my BSRT Help start the RRT lead asthma program at UNMH Currently working in Interventional Pulmonary at UNMH I M A LITTLE BIT OF A GEEK
F e N O
NOT NITROUS OXIDE
History of Nitric Oxide
JOSEPH PRIESTLY 1703-1804 Nitric Oxide (1772) Nitrogen Dioxide Nitrous Oxide Hydrogen Chloride Ammonia Sulfur Dioxide Silicon Tetrafluoride Nitrogen Oxygen (Co-discovered with Carl Wilhelm Scheele) Carbon Monoxide
1977 Ferid Murad and his group published an article titled, Nitric oxide activates guanylate cyclase and increases guanosine 3 :5 -cyclic monophosphate levels in various tissue preparations Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3 :5 -cyclic monophosphate levels in various tissue preparations. Proceedings of the National Academy of Sciences of the United States of America. 1977;74(8):3203-3207.
1980 Robert Furchgott and partner Zawadzki published, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Furchgott RF, Zawadzki JV.
1987 Luis J. Ignarro publishes, The Identification of Nitric Oxide as Endothelium-derived Relaxing Factor Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proceedings of the National Academy of Sciences of the United States of America. 1987;84(24):9265-9269.
1991 Pepke-Zaba et al. publishes, Inhaled nitric oxide as a cause of selective pulmonary vasodilator in pulmonary hypertension. Pepke-Zaba J, Hibenbottam TW, Dinh-Xaun AT, Stone D, and Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilator in pulmonary hypertension. Lancet 338: 1173-1174, 1991
1992 Nitric Oxide is name Molecule of the Year by Science Magazine The molecule of the year BY DE KOSHLAND JR SCIENCE18 DEC 1992 : 1861
1993-1994 Gustafsson et al. Lundberg et al. Stamler et al. Barnes et al. Elevated Exhaled Nitric Oxide in Allergen-Provoked Asthma Is Associated with Airway Epithelial inos. Abraham B. Roos, Michiko Mori, Reidar Grönneberg, Christina Österlund, Hans-Erik Claesson, Jan Wahlström, Johan Grunewald, Anders Eklund, Jonas S. Erjefält, Jon O. Lundberg, Magnus Nord Published: February 28, 2014
1 9 9 8 N O B E L P R I Z E
F R O M T H E PA S T T O T H E P R E S E N T
T H E B O D Y S R E G U L AT I O N O F N I T R I C OX I D E
CONSTITUTIVE NEURONAL nnos Calcium dependent Localized in airway nerves Present in airway smooth muscle Density decreases from the trachea to the small bronchi Present around submucosal glands Fabio LM, Ricciardolo PJ, Sterk BG, Gert F. Nitric Oxide in Health and Disease of the Respiratory System. Physiol Rev 84: 731-765, 2004
INDUCIBLE inos Calcium independent Localized to macrophages Fabio LM, Ricciardolo PJ, Sterk BG, Gert F. Nitric Oxide in Health and Disease of the Respiratory System. Physiol Rev 84: 731-765, 2004 Can be expressed in alveolar type II cells, lung fibroblasts, airway respiratory epithelial cells, mast cells, endothelial cells, neutrophils and chondrocytes
CONSTITUTIVE ENDOTHELIAL enos Calcium dependent Expressed in bronchial epithelium and type II alveolar epithelial cells Also localized in the nasal mucosa and the basal membrane of ciliary microtubules Fabio LM, Ricciardolo PJ, Sterk BG, Gert F. Nitric Oxide in Health and Disease of the Respiratory System. Physiol Rev 84: 731-765, 2004
F e N O & AIRWAY INFLAMMATION
BRONCHIAL ALVEOLAR LAVAGE Increased exhaled nitric oxide Increase in eosinophils Warke T, Fitch P, Brown V, et al. Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax. 2002;57(5):383-387. doi:10.1136/thorax.57.5.383.
LUNG BIOPSIES Relationship between Exhaled Nitric Oxide and Mucosal Eosinophilic Inflammation in Children with Difficult Asthma, after Treatment with Oral Prednisolone. DONALD N. R. PAYNE, IAN M. ADCOCK, NICOLA M. WILSON, TIM OATES, MICHAEL SCALLAN, and ANDREW BUSH. https://doi.org/10.1164/ajrccm.164.8.2101145 PubMed: 11704581 Received: January 30, 2001 Accepted: June 11, 2001
INDUCED SPUTUM Eosinophil count > 3% FeNO > 8.3ppb The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Berry MA1, Shaw DE, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. Clin Exp Allergy. 2005 Sep;35(9):1175-9.
F e N O FACTORS AFFECTING VALUES
Factors Affecting FeNO Values Age and/or sex Spirometry maneuvers ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. Am J Respir Crit Care Med Vol 171. 9123-930, 2005
Factors Affecting FeNO Values Airway caliber Food and beverages ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. Am J Respir Crit Care Med Vol 171. 9123-930, 2005
Factors Affecting FeNO Values Circadian rhythm Smoking ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. Am J Respir Crit Care Med Vol 171. 9123-930, 2005
Factors Affecting FeNO Values Infection Medications ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. Am J Respir Crit Care Med Vol 171. 9123-930, 2005
AT S RECOMMENDATIONS Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
ATS RECOMMENDATIONS We recommend the use of FeNO in the diagnosis of eosinophilic airway inflammation. We recommend the use of FeNO in determining the likelihood of steroid responsiveness in individuals with chronic respiratory symptoms possible due to airway inflammation. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
ATS RECOMMENDATIONS We suggest that FeNO may be used to support the diagnosis of asthma in situations in which objective evidence is needed. We suggest the use of cut points rather than reference values when interpreting FeNO levels. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
ATS RECOMMENDATIONS We recommend accounting for age as a factor affecting FeNO in children younger than 12 years of age. We recommend that low FeNO (< 25ppb) be used to indicate that eosinophilic inflammation and responsiveness to corticosteroids are less likely. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
ATS RECOMMENDATIONS We recommend that FeNO (> 50ppb) be used to indicate that eosinophilic inflammation and in symptomatic patients, responsiveness to corticosteroids are likely. We recommend that FeNO values between 25ppb and 50ppb should be interpreted cautiously with reference to the clinical context. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
ATS RECOMMENDATIONS We recommend accounting for persistent and/or high allergen exposure as a factor associated with higher levels of FeNO. We recommend the use of FeNO in monitoring airway inflammation in patients with asthma. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):602-615. doi:10.1164/rccm.9120-11st.
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