Clinical Utility of Central and Peripheral Airway Nitric Oxide in Aging Patients with Stable and Acute Exacerbated Chronic Obstructive Pulmonary Disease

Abstract

Xiaodong Fan,1,* Nian Zhao,2,3,* Zhen Yu,1 Haoda Yu,1 Bo Yin,1 Lifei Zou,1 Yinying Zhao,1 Xiufen Qian,1 Xiaoyan Sai,1 Chu Qin,1 Congli Fu,1 Caixia Hu,1 Tingting Di,1 Yue Yang,1 Yan Wu,1 Tao Bian1 1Departments of Pulmonary and Critical Care Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 2Departments of Pulmonary and Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, 215300, People’s Republic of China; 3The first medical college of Nanjing Medical University, NanJing, Jiangsu, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Wu; Tao BianDepartment of Pulmonary and Critical Care Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of ChinaEmail [email protected]; [email protected]: Exhaled nitric oxide has been used as a marker of airway inflammation. The NO concentration in the central and peripheral airway/alveolar can be measured by a slow and fast exhalation flow rate to evaluate inflammation in different divisions within the respiratory tract. We hypothesized that FeNO200 (exhaled NO at a flow rate of 200mL/s) could be used as an evaluation tool for peripheral airway/alveolar inflammation and corticosteroid therapy in chronic obstructive pulmonary disease (COPD) patients.Methods: We recruited 171 subjects into the study: 73 healthy controls, 59 stable COPD patients, and 39 acute exacerbations of COPD (AECOPD) patients. Exhaled nitric oxide (FeNO50 (exhaled NO at a flow rate of 50mL/s)), FeNO200 and CaNO (peripheral concentration of NO/alveolar NO) and clinical variables including pulmonary function, COPD Assessment Test (CAT), C-reactive protein concentration (CRP) and circulating eosinophil count were measured among the recruited participants. FeNO50, FeNO200 and CaNO were repeatedly evaluated in 39 AECOPD patients after corticosteroid treatment.Results: FeNO200 was significantly higher in stable COPD and AECOPD patients than in healthy controls. Nevertheless, CaNO could not differentiate COPD from healthy controls. No correlation was found between circulating eosinophil counts or FEV1 and exhaled nitric oxide (FeNO50, FeNO200, CaNO) in COPD patients. For AECOPD patients, 64% of patients had eosinophil counts > 100 cells/μL; 59% of patients had FeNO200 > 10 ppb; only 31% of patients had FeNO50 > 25 ppb. Among AECOPD patients, the high FeNO50 and FeNO200 groups’ levels were significantly lower than their baseline levels, and significant improvements in CAT were seen in the two groups after corticosteroid treatment. These implied a good corticosteroid response in AECOPD patients with FeNO200> 10ppb.Conclusion: FeNO200 is a straightforward and feasible method to evaluate the peripheral NO concentration in COPD. FeNO200 can be a type 2 inflammation biomarker and a useful tool for predicting corticosteroid therapy in COPD.Keywords: exhaled nitric oxide, chronic obstruction pulmonary disease, corticosteroid, biomarker

Keywords

• exhaled nitric oxide
• chronic obstruction pulmonary disease
• corticosteroid
• biomarker