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FeNO

B Y L E S L I E K U M P F, R RT, C P F T, A E - C

I’M A LITTLE BIT OF A GEEK

• 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

LESLIE KUMPF RRT, CPFT, AE-C

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.

1991Pepke-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 yearBY DE KOSHLAND JR

SCIENCE18 DEC 1992 : 1861

1993-1994Gustafsson 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 TO 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 OXI D E

CONSTITUTIVE NEURONALnNOS

• 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

• Can be expressed in

alveolar type II cells, lung

fibroblasts, airway

respiratory epithelial

cells, mast cells,

endothelial cells,

neutrophils and

chondrocytesFabio LM, Ricciardolo PJ, Sterk BG, Gert F. Nitric Oxide in Health and Disease of the Respiratory System. Physiol Rev 84: 731-765, 2004

CONSTITUTIVE ENDOTHELIALeNOS

• 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

INDUCEDSPUTUM

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


Airway caliber

Food and beverages




Circadian rhythm

Smoking




Infection

Medications



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.”



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.”



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.”



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.”



F R O M T H E P R E S E N T TO T H E F U T U R E

TA K E AWAY S

T H A N K Y O UL E S L I E K U M P F R R T , C P F T , A E - C

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