Ana F. Trueba

Acute Stress–induced Increases in Exhaled Nitric Oxide in Asthma and Their Association with Endogenous Cortisol

RATIONALE psychosocial stress is known to influence the pathophysiology of asthma. Although stress has been linked to serum markers of inflammatory activity and exaggerated response to allergen challenge in asthma, few studies have examined inflammatory activity in the airways linked to psychosocial stress alone. Furthermore, although studies have demonstrated lower levels or reactivity of endogenous cortisol in asthma, the association with airway inflammatory activity in stress remains unexplored. OBJECTIVES we therefore studied airway inflammation and cortisol response to a standardized laboratory task inducing acute psychosocial stress. METHODS airway inflammation by the fraction of exhaled nitric oxide (FeNO) and saliva cortisol were sampled before and up to 45 minutes after experimental challenge with the Trier Social Stress Test in 20 adult patients with asthma and 19 healthy control subjects. Respiratory inductive plethysmography was used to control for changes in ventilatory activity that impact FeNO levels. MEASUREMENTS AND MAIN RESULTS FeNO levels were generally higher in patients with asthma than healthy control subjects and salivary cortisol levels were lower. Increases in cortisol levels were observed after the stress protocol in both groups (P < 0.001). FeNO levels at the time of peak cortisol increase after stress were significantly higher than before stress in both groups (P < 0.05). FeNO increases were independent of changes in ventilation. In patients with asthma, higher cortisol levels and stronger increases in cortisol after stress were significantly associated with smaller increases in FeNO (P < 0.05). CONCLUSIONS acute psychosocial stress alone increases airway inflammatory markers and this increase is attenuated by stronger stress-related activity of the hypothalamic-pituitary-adrenal axis in asthma.

Psychosocial factors and behavioral medicine interventions in asthma.

OBJECTIVE This review examines the evidence for psychosocial influences in asthma and behavioral medicine approaches to its treatment. METHOD We conducted a systematic review of the literature on psychosocial influences and the evidence for behavioral interventions in asthma with a focus on research in the past 10 years and clinical trials. Additional attention was directed at promising new developments in the field. RESULTS Psychosocial factors can influence the pathogenesis and pathophysiology of asthma, either directly through autonomic, endocrine, immunological, and central nervous system mechanisms or indirectly through lifestyle factors, health behaviors, illness cognitions, and disease management, including medication adherence and trigger avoidance. The recent decade has witnessed surging interest in behavioral interventions that target the various pathways of influence. Among these, self-management training, breathing training, and exercise or physical activation programs have proved particularly useful, whereas other essential or promising interventions, such as smoking cessation, dietary programs, perception and biofeedback training, and suggestive or expressive psychotherapy, require further, more rigorous evaluation. Given the high comorbidity with anxiety and mood disorders, further evaluation of illness-specific cognitive behavior therapy is of particular importance. Progress has also been made in devising community-based and culturally tailored intervention programs. CONCLUSION In concert with an essential medication treatment, behavioral medicine treatment of asthma is moving closer toward an integrated biopsychosocial approach to disease management.

Academic exam stress and depressive mood are associated with reductions in exhaled nitric oxide in healthy individuals

Nitric oxide (NO) has beneficial effects on cardiovascular and immune health. Stress and depression have been linked to a reduction in serum NO. In this study, we examined the effect of academic exam stress on the fraction of NO in exhaled air (FeNO) and spirometric lung function in 41 healthy college students. Participants completed assessments at mid-semester as well as in the early and late phase of an academic exam period. Negative affect, depressive mood, and salivary cortisol were elevated during exams, whereas FeNO and lung function decreased. Higher depressive mood was associated with lower FeNO, whereas higher negative affect was associated higher FeNO across time. These findings provide initial evidence that depression and prolonged stress can alter FeNO and lung function in healthy individuals, which could have adverse consequences for cardiovascular, airway, and immune health.

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.

Behavioral Medicine Approaches to Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease and associated with considerable individual and socioeconomic burden. Recent research started examining the role of psychosocial factors for course and management of the disease.PurposeThis review provides an overview on recent findings on psychosocial factors and behavioral medicine approaches in COPD.ResultsResearch has identified several important psychosocial factors and effective behavioral medicine interventions in COPD. However, there is considerable need for future research in this field.ConclusionsAlthough beneficial effects of some behavioral medicine interventions have been demonstrated in COPD, future research efforts are necessary to study the effects of distinct components of these interventions, to thoroughly examine promising but yet not sufficiently proven interventions, and to develop new creative interventions.

Stress, asthma, and respiratory infections: Pathways involving airway immunology and microbial endocrinology

Stress and infections have long been independently associated with asthma pathogenesis and exacerbation. Prior research has focused on the effect of psychological stress on Th cells with particular relevance to atopic asthma. In this review, we propose new perspectives that integrate the role of infection in the relationship between psychological stress and asthma. We highlight the essential role of the mucosal epithelia of the airways in understanding the interaction between infections and the stress-asthma relationship. In addition, we review findings suggesting that psychological stress not only modulates immune processes, but also the pathogenic qualities of bacteria, with implications for the pathogenesis and exacerbation asthma.

Effects of psychosocial stress on the pattern of salivary protein release

Previous research suggests that acute stress can increase the release of immune-relevant proteins in saliva. However, no attempts have been made to examine a wider range of salivary proteins in response to stress. In this study, we identified and quantified changes in the pattern of salivary protein release in a 45 min time period following the Trier Social Stress Test (TSST) in 12 asthmatic and 13 healthy participants. Proteins were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The relative protein amounts were quantified using the Image J software (NIH), and identified and characterized using mass spectroscopy. Negative affect was increased immediately after stress in both groups. The results showed that alpha amylase, cystatin S and light chain IgA were increased after the TSST and significant increases in glutathione S-transferase and prolactin inducible protein were also observed. Asthma patients showed responses similar to healthy controls, but had a tendency toward overall lower alpha amylase levels. Our findings suggest that a variety of proteins relevant to mucosal immunity are elevated following acute psychosocial stress, including glutathione S-transferase and prolactin inducible protein, which had not been characterized in this context before.

High cortisol awakening response and cortisol levels moderate exposure-based psychotherapy success

BACKGROUND Research suggests that elevated stress hormones during exposure can facilitate fear extinction in laboratory settings. However, prospective studies on the clinical benefits of endogenous cortisol on clinical improvements in naturalistic exposures are lacking. METHODS Twenty-six patients with panic disorder and agoraphobia completed three weekly in-vivo exposure sessions and a fourth session 2 months following therapy completion, resulting in a total of 94 in-vivo exposure sessions. Salivary cortisol was collected at multiple times during the first exposure day (cortisol morning response, prior, -during, -after exposure) and at subsequent exposure sessions (prior, -during, -after exposure). Cortisol collection on a non-exposure comparison day followed the same time schedule as session 1. RESULTS Exposure day anxiety and cortisol levels were significantly higher than control day levels. Higher absolute cortisol levels during exposures moderated clinical improvement (avoidance behavior, threat appraisal, perceived control). Therapeutic gains were not just related to exposure day cortisol levels, but were also linked to non-exposure day levels. Greater morning rises in cortisol on exposure day predicted greater treatment gains, but greater rises on the control day were associated with poorer outcomes. CONCLUSIONS The study provides first evidence for a moderating effect of cortisol awakening response and absolute cortisol levels on fear extinction processes during naturalistic, prospective exposure-therapy. Additionally, we replicated and extended prior findings on the therapeutic benefits of high exposure cortisol levels. Together, the findings suggest that cortisol may act as a general moderator of facilitated learning during exposure therapy.

Increases in exhaled nitric oxide after acute stress: association with measures of negative affect and depressive mood.

Background Increases in fractional exhaled nitric oxide (FeNO) have been observed after acute laboratory stress, which could indicate a strengthening of immune defenses in acute stress because of the quick onset of the response and the role of nitric oxide in airway-protective functions. In addition, because sustained psychological distress and depression are known to deteriorate immune defenses systems, they may dampen the FeNO response to acute stress. Methods FeNO and negative affect were measured before and after a speech and mental arithmetic stressor. We examined the association of stress-induced FeNO changes with momentary negative affect and questionnaires of perceived stress, anxious mood, and depressive mood in 39 asthma patients and 41 healthy controls. Results FeNO increased from baseline to stress in participants with asthma (from 3.38 [0.102] to 3.46 [0.103] ln(ppb)) and controls (2.86 [0.098] to 2.92 [0.099]; F(4,141) = 3.26, p = .014), but the magnitude of the FeNO response did not differ between groups (F < 1). Only low levels of depressive mood were associated with FeNO increases after stress (most pronounced at 0 minute poststress; t(76) = 3.87, p < .001). In contrast, only higher perceived stress was associated with FeNO increases (most pronounced at 0 minute poststress; t(75) = 4.09, p < .001), and momentary negative affect was associated with higher FeNO throughout assessments (&bgr; = 0.08, t(114) = 8.27, p = .005). Associations of FeNO with psychological variables were largely unrelated to asthma status and inhaled corticosteroid use. Conclusions Depressive mood is associated with a reduced mobilization of airway nitric oxide in acute stress, whereas other indicators of negative affect are positively associated with overall FeNO levels and reactivity.

Exhaled Nitric Oxide Decreases during Academic Examination Stress in Asthma.

RATIONALE Fractional exhaled nitric oxide (FeNO) is known to vary with multiple endogenous and exogenous factors. Laboratory stress and depressive mood have been associated with altered FeNO levels, but little is known about the susceptibility of FeNO to longer-lasting states of psychological stress in asthma. OBJECTIVES We sought to study changes in FeNO, lung function, and endogenous cortisol levels in students in a low-stress period during the academic term and in high-stress periods of up to 5 days during final exams. METHODS One hundred nine participants (35 with asthma) enrolled in a final examination stress study were assessed during the academic term (low stress) and during final exams (high stress). FeNO, spirometric lung function (FEV1, peak flow), salivary cortisol, and negative affect were measured at three time points. Control variables were medication use, cold symptoms, sex, and age. MEASUREMENTS AND MAIN RESULTS FeNO decreased substantially from low-stress baseline to the high-stress examination periods, with more pronounced decreases occurring in subjects with asthma (-11.5 ppb) than control subjects (-1.2 ppb). FEV1 decreased in both groups. Negative affect and cortisol increased during final exams, but these increases were smaller in asthma. Greater initial depression and greater cortisol increases were related to larger FeNO decreases during the final exam period, the latter only in asthma. Inhaled corticosteroid use did not affect these changes. CONCLUSIONS Psychological stress and depressive mood are accompanied by decreases in both FeNO and lung function in asthma. Fluctuations related to life stress and mood levels should be considered in FeNO monitoring for asthma.