Fractional Exhaled Nitric Oxide (FeNO) in Patients with Stable Chronic Obstructive Pulmonary Disease: Short-Term Variability and Potential Clinical Implications

Pasquale Ambrosino; Salvatore Fuschillo; Mariasofia Accardo; Marco Mosella; Antonio Molino; Giorgio Alfredo Spedicato; Andrea Motta; Mauro Maniscalco

doi:10.3390/jpm12111906

Fractional Exhaled Nitric Oxide (FeNO) in Patients with Stable Chronic Obstructive Pulmonary Disease: Short-Term Variability and Potential Clinical Implications

J Pers Med. 2022 Nov 16;12(11):1906. doi: 10.3390/jpm12111906.

Authors

Pasquale Ambrosino¹, Salvatore Fuschillo², Mariasofia Accardo², Marco Mosella², Antonio Molino³, Giorgio Alfredo Spedicato⁴, Andrea Motta⁵, Mauro Maniscalco^{2

3}

Affiliations

¹ Istituti Clinici Scientifici Maugeri IRCCS, Cardiac Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy.
² Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy.
³ Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.
⁴ Department of Statistics and Quantitative Methods, Milano-Bicocca University, 20126 Milan, Italy.
⁵ Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy.

Abstract

Background: The use of fractional exhaled nitric oxide (FeNO) has been proposed for identifying and monitoring eosinophilic airway inflammation in chronic obstructive pulmonary disease (COPD). To explore the clinical utility of FeNO in COPD, we aimed to assess its short-term variability in a clinically stable COPD cohort.

Methods: Consecutive COPD patients, formerly smokers, underwent FeNO assessment at the baseline and six time-points through serial sampling spaced 3 days apart.

Results: A total of 41 patients (mean age 72.9, 87.8% males) showed a median baseline value of FeNO of 11.7 (8.0-16.8) ppb. A weak linear relationship was documented between baseline FeNO values and both eosinophil counts (r = 0.341, p = 0.029) and the percentage of eosinophils (r = 0.331, p = 0.034), confirmed in multiple linear regressions after adjusting for steroid use. The overall individual variability of FeNO between time-points was 3.90 (2.53-7.29) ppb, with no significant difference in the distribution of FeNO values measured at different time-points (p = 0.204). A total of 28 (68.3%) patients exhibited FeNO always below the 25 ppb cut-off at all determinations, while the remining 13 (31.7%) had at least one value above the established limit. Interestingly, none of these 13 participants had FeNO stably above 25 ppb, all showing at least one normal value during serial sampling. Compared to these patients with more fluctuating values, the 28 with stably normal FeNO only exhibited a significantly higher body weight (80.0 ± 18.2 kg vs. 69.0 ± 8.8 kg, p = 0.013) and body mass index (29.7 ± 6.5 kg/m² vs. 25.9 ± 3.7 kg/m², p = 0.026), confirmed in multiple logistic regressions after adjusting for major potential confounders.

Conclusions: A certain degree of FeNO variability, apparently unrelated to eosinophil counts but somehow influenced by body weight, must be considered in COPD patients. Further studies are needed to clarify whether this biomarker may be effectively used to plan more personalized pharmacological and rehabilitation strategies in this clinical setting.

Keywords: biomarker; chronic disease; chronic obstructive pulmonary disease; disability; exercise; nitric oxide; outcome; rehabilitation.

Grants and funding

This work was partially supported by the “Ricerca Corrente” funding scheme of the Ministry of Health, Italy.