Airway nitric oxide and psychological processes in asthma and health: A review

Objective The fraction of exhaled nitric oxide (FeNO) has been widely used as a marker of airway inflammation in asthma in recent years. However, NO serves multiple functions throughout the organism, and various influences on FeNO levels beyond inflammation have been documented. Emerging literature indicates that psychological processes are systematically linked to FeNO. Data Sources Academic Search Complete, PubMed, PsychArticles, and PsychInfo databases. Study Selections Relevant studies were identified using keywords exhaled nitric oxide paired with psychological stress, stress psychology, emotion, major depression, anxiety, or psychopathology. Studies measuring FeNO during naturalistic observation of emotion and stress, laboratory stress and emotion-induction protocols, and correlational designs using psychological questionnaires were included. Results Acute stress, anxiety, and negative affect have been repeatedly linked with higher FeNO levels, whereas more prolonged states of stress, in particular depression, have been associated with lower FeNO levels. The literature on FeNO is paralleled by research on NO in the cardiovascular and central nervous systems, which also shows systematic associations with psychosocial variables. Potential mechanisms of association include stimulation of NO release from different cells, including the epithelia and macrophages, through noradrenaline, interferon-γ, or vascular endothelial growth factor, changes in oxidative stress or arginase levels, or facilitation of diffusion by mechanical factors. Conclusion Psychosocial factors may need to be considered in the interpretation of longitudinal FeNO changes in monitoring and management of patients with asthma. The distinction between constitutive and inducible sources of NO will be essential for future research.