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

Abstract

Purpose: 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. FeNO_50, 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 (FeNO_50, 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: biomarker; chronic obstruction pulmonary disease; corticosteroid; exhaled nitric oxide.

Figure 1

Exhaled nitric oxide in healthy controls, stable and exacerbated COPD patients. FeNO₅₀ increased in stable and exacerbated COPD patients (A). FeNO₂₀₀ increased in stable and exacerbated COPD patients (B). There was no significant difference of CaNO in healthy controls, stable and exacerbated COPD patients (C).

Figure 2

Changes in FeNO₅₀, FeNO₂₀₀ and CaNO in different groups. FeNO₅₀ in patients with initial FeNO₅₀> 25 ppb decreased after treatment (A), FeNO₅₀ in patients with initial FeNO₅₀ ≤ 25 ppb did not change after treatment (B), FeNO₂₀₀ in patients with initial FeNO₂₀₀> 10 ppb decreased after treatment (C), FeNO₂₀₀ in patients with initial FeNO₂₀₀ ≤ 10 ppb did not change after treatment (D), CaNO in patients with initial CaNO > 5 ppb did not change after treatment (E), CaNO in patients with initial CaNO ≤ 5 ppb did not change after treatment (F).

Figure 3

FeNO₅₀, FeNO₂₀₀ and CaNO in healthy controls and COPD patients of different severity according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). FeNO₅₀ was not correlated with different GOLD stages (A). FeNO₂₀₀ was not correlated with GOLD stages (B). CaNO was elevated at stage of GOLD4 (C).