How does smoking affect FeNO?

Current smoking rates amongst asthmatic patients in the USA and UK range from 17-35%, despite its association with an accelerated decrease in lung function and increase in severe symptoms. ^4,5 Smoking has been well-documented as a factor which causes a decrease in endogenous nitric oxide (NO) production in the lung epithelium, which has been shown to decrease FeNO levels by 30-60% in smoking asthmatics compared to non-smoking asthmatics. ^2,6 This can mean that a patients FeNO level may not be a clear representation of the inflammation present in the lungs, which could pose a challenge with asthma management.

Fractional exhaled nitric oxide (FeNO) testing is a quick measure of lung inflammation and works by measuring the level of exhaled NO in the patient’s breath, which is typically upregulated in some types of asthma.^7,8 In Type 2 asthma patients, the pathway of increased nitric oxide levels is facilitated by an increase in inflammatory cytokines such as IL-4 and IL-13, leading to an overproduction of airway NO.⁹ This is used to help diagnose asthma, monitor disease progression, and identify which patients will respond to anti-inflammatory treatment and doses, with increases in FeNO being associated with a deterioration in disease control.^10-12

The challenge faced when measuring FeNO level in patients who smoke is that the process of endogenous NO production is dysregulated in the lung.¹³

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How does smoking affect FeNO?

Smoking is associated with decreased endogenous NO production and increased oxidative stress, which can cause damage to the lung epithelium.^3,13 When cigarette smoke is inhaled into the lung, this causes a reduction in cytokine-induced inducible NO synthase (iNOS) protein expression in lung epithelial cells, which downregulates the inflammatory process, causing a decrease in endogenous NO production.^{14, 16}

Studies have shown that FeNO levels in asthma patients who smoke are significantly lower than in patients who have never smoked, however, FeNO can still be used to differentiate asthmatic patients from non-asthmatic patients in never smoking and current smoking patients ^1,2.

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References:

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Malinovschi A. Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters. European Respiratory Journal. 2006 1;28(2):339–45.
Horváth I, et al. Exhaled Nitric Oxide and Hydrogen Peroxide Concentrations in Asthmatic Smokers. Respiration. 2004;71(5):463–8.
Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. European respiratory journal. 2004 Nov 1;24(5):822-33.
NHS England. Hospital admissions due to smoking up nearly 5% last year, NHS data shows. Available at: https://www.england.nhs.uk/2023/12/hospital-admissions-due-to-smoking-up-nearly-5-per-cent-last-year-nhs-data-shows/. Accessed: July 2024.
Prof. Kjell Alving. Factors affecting FeNO: confounders vs determinants. Available at; https://www.niox.com/prof-alving-webinar/
Ali H, et al. The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma. South East European Journal of Immunology. 2023;6(1):18-23.
Busse W et al. Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled, moderate-to-severe asthma receiving placebo in the LIBERTY ASTHMA QUEST study: a post-hoc analysis. The Lancet Respiratory Medicine. 2021;9(10):1165-73.
Escamilla-Gil JM, et al. Understanding the Cellular Sources of the Fractional Exhaled Nitric Oxide (FeNO) and Its Role as a Biomarker of Type 2 Inflammation in Asthma. BioMed Research International. 2022 2;2022:1–9.
Ulrik CS, et al. Fractional exhaled nitric oxide as a determinant for the clinical course of asthma: a systematic review. European Clinical Respiratory Journal. 2021 1;8(1).
Smith AD, et al. Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma. New England Journal of Medicine. 2005 26;352(21):2163–73.
Jones SL, et al. The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control. Am J Respir Crit Care Med2001;164:738-743
Balint B, et al. Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke. Thorax. 2001 1;56(6):456–61.
Hoyt JC, et al. CIGARETTE SMOKE DECREASES INDUCIBLE NITRIC OXIDE SYNTHASE IN LUNG EPITHELIAL CELLS. Experimental Lung Research. 2003 2;29(1):17–28.
Kharitonov SA, et al. Acute and chronic effects of cigarette smoking on exhaled nitric oxide. American Journal of Respiratory and Critical Care Medicine. 1995 ;152(2):609–12.
Ahovuo-Saloranta A, et al. Basic characteristics and clinical value of FeNO in smoking asthmatics—a systematic review. Journal of Breath Research. 2019 3;13(3):034003.
Polosa R, et al. Smoking and asthma: dangerous liaisons. European Respiratory Journal. 2013;41(3):716–26.
HÖGMAN M, et al. Increased nitric oxide elimination from the airways after smoking cessation. Clinical Science. 2002 1;103(1):15–9.
Health Innovation Network. Fractional Exhaled Nitric Oxide (FeNO) guidance for Primary Care. Available at: https://healthinnovationnetwork.com/wp-content/uploads/2022/08/South-West-Respiratory-Network-FeNO-Guidance-April22.pdf