Role of alveolar nitric oxide in gastroesophageal reflux-associated cough: prospective observational study.

ABSTRACT

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC). OBJECTIVES: We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC. DESIGN: This is a single-center prospective observational study. METHODS: FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO. RESULTS: CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb versus 2.8 ± 2.3 ppb, p < 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15 versus 9 ± 9 episodes, p = 0.001) and a higher level of pepsin (984.8 ± 492.5 versus 634.5 ± 626.4 pg/ml, p = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ2 = 3.963, p = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 versus 4.8 ± 2.6 ppb, p < 0.001). CONCLUSION: Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.

Role of CaNO in GERCWhy was the study done? This study aimed to investigate the role of concentration of alveolar nitric oxide (CaNO) as a biomarker for peripheral airway inflammation in patients with gastroesophageal reflux-associated cough (GERC). The evaluation of airway inflammation in GERC has not been widely practiced in clinical settings, and the potential of CaNO as a biomarker remained unclear.What did the researchers do? The researchers conducted a prospective study involving patients diagnosed with GERC and compared the changes in CaNO levels between GERC patients and those with cough due to other causes. The study also identified potential factors contributing to elevated CaNO levels in GERC patients relative to the normal range. Additionally, CaNO level changes were evaluated in a subgroup of GERC patients with initially elevated CaNO levels (n = 26).What did the researchers find? The study found that CaNO levels were significantly increased in GERC patients. Using a reference value for normal CaNO, the GERC patients were divided into a high CaNO cohort and a normal CaNO cohort. More proximal reflux episodes and higher level of pepsin in sputum supernatant were observed in the high CaNO cohort. Moreover, CaNO demonstrated moderate predictive value for the therapeutic efficacy of intensified anti-reflux therapy in GERC patients. After several weeks of anti-reflux therapy, CaNO levels significantly decreased along with the resolution of cough. These findings further confirmed the predictive value of CaNO for anti-reflux therapy.What do the findings mean? The findings suggest that CaNO may have the potential to be used as a non-invasive biomarker for detecting peripheral airway inflammation in GERC patients. Increased CaNO may be associated with potential micro-aspiration. Furthermore, high CaNO may predict the need for intensified anti-reflux therapy.