A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation

Abstract

Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. Results: The proportions of patients with technically acceptable measurements at 10–30–50–100–150–200–250–300 mL/s exhalation flow rates were 8–58–100–98–98–95–90–80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100–150–200–250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83–2.97/vs. 0.70/0.54–0.87/nL/s, p < 0.001) and CANO (4.08/2.63–7.16/vs. 2.42/1.83–2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF_25-75% (p = 0.02, r = –0.36) and DL,CO (r = –0.46, p = 0.004). JawNO was not related to lung function parameters. Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100–250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma.

Keywords:

• Airway inflammation
• exhaled biomarker
• extended nitric oxide analysis
• disease monitoring
• severe asthma

Acknowledgements

We thank the kind participation of patients and control volunteers in this study. The authors are thankful to Mr. Sándor Nyágúj for measuring lung function. We would like to acknowledge the assistance of Dr. Anikó Bohács and Dr. Ibolya Czaller in patient recruitment.

Additional information

Funding

This study was funded by the Bolyai Research Grant of the Hungarian Academy of Sciences (BO/00559/16 to Dr. Zsófia Lázár, BO/00262/15 to Dr. András Bikov), the Scientific Grant of the Hungarian Respiratory Society (MPA/2014 to Dr. Zsófia Lázár) and the Hungarian National Research, Development and Innovation Fund's (PuBioRep research project to Prof. György Losonczy).