Exhaled nitric oxide measurement in patients with connective tissue diseases associated with interstitial lung disease: a narrative review

: FactsMost evidence on exhaled nitric oxide measurement in patients with connective tissue diseases associated with interstitial lung disease is focused on systemic sclerosis.In systemic sclerosis, the alveolar nitric oxide concentration may serve as a marker of interstitial lung disease and may reflect inflammatory activity, with potential implications for disease monitoring and therapeutic decision-making.Alveolar nitric oxide concentration may contribute to the phenotypic characterization of interstitial lung diseases and help distinguish those associated with connective tissue disease from other subsets.Open QuestionsThe potential influence of factors such as smoking, obesity, and the presence of pulmonary hypertension on exhaled nitric oxide should be further investigated in patients with connective tissue disease-associated interstitial lung disease.The levels and clinical value of the alveolar nitric oxide concentration in patients with interstitial lung disease secondary to connective tissue diseases other than systemic sclerosis warrant further investigation.Standardization of the methodology for determining alveolar nitric oxide concentration, as well as comparison of results obtained using the same device and analytical model, appears fundamental.The minimum clinically important difference in the alveolar nitric oxide concentration in patients with connective tissue disease-associated interstitial lung disease still needs to be defined. Connective tissue diseases are a group of different conditions frequently associated with interstitial lung disease, a complication with significant morbidity and mortality implications. Given its high incidence and clinical impact, an early and accurate diagnosis of interstitial lung disease is crucial. High-resolution computed tomography of the chest and pulmonary function tests is essential for diagnosing and monitoring interstitial lung disease, but in recent years, many studies have been conducted to identify new potential biomarkers. Among these, nitric oxide in exhaled air has drawn much attention, mainly because it is non-invasive, rapid and relatively low in cost. In this narrative review, we summarize published evidence regarding exhaled nitric oxide assessment in interstitial lung disease associated with connective tissue disease in adults, starting from the role of the molecule and the measurement technique. Most of the published studies have focused on interstitial lung disease associated with systemic sclerosis, which is the subject of the central part of the review. Under these conditions, measurements of exhaled nitric oxide levels, particularly its alveolar concentration, have been shown to correlate with the presence of interstitial lung disease and to predict its progression and response to treatment. Although most evidence is related to interstitial lung disease associated with systemic sclerosis, the results are also becoming available for other interstitial lung diseases associated with connective tissue disease. Despite promising results, exhaled nitric oxide measurement is not yet part of routine clinical practice. Further studies are needed to validate its role and integrate it into the clinical management of patients with interstitial lung disease associated with connective tissue disease.