Social support, exhaled nitric oxide, and upper respiratory symptoms in health and asthma.

Accumulating research identifies a role of psychological process, particularly negative affect, in the expression of airway nitric oxide (NO), yet directional associations tend to vary across methodologies and samples. Recent findings indicate higher social support to be associated with higher airway NO; however, consequences for respiratory infection remain unexplored. NO has a key role in the first line of epithelial defense against pathogens, thus, social support could unfold airway protective effects through enhanced production of NO. We therefore examined the associations among social support, negative affect, airway NO, and cold symptoms in a sample of undergraduate students. In this cross-sectional study, 637 participants completed questionnaires of social support, negative affect, medical history, and current cold symptoms followed by measurements of fractional exhaled NO (FENO) to study airway NO during a semester period of relative low stress. Findings showed that greater social support was associated with higher FENO and fewer cold symptoms, controlling for key covariates. Further analysis suggested an additional indirect effect of social support on FENO through cold symptoms such that higher social support was related to lower cold symptoms, which were related to lower FENO. These results, coupled with longitudinal findings in the previous research, suggest that social support can affect FENO and cold symptoms through a complex pattern of direct and indirect effects. Overall, findings support the role of psychological processes - particularly social support - as relevant to FENO and cold symptoms in young adults.

Beetroot juice supplementation for the prevention of cold symptoms associated with stress: A proof-of-concept study.

OBJECTIVES: Psychological stress has been linked to common cold symptoms. Nitric oxide (NO) is part of the first line of epithelial defense against pathogens, and beetroot juice is a source of dietary nitrate that increases NO availability. We therefore tested whether beetroot juice protects against cold symptoms in a period of sustained acute stress. DESIGN: Seventy-six students, 16 of these with asthma, were randomly assigned to seven daily doses of beetroot juice or no supplementation control during their final exams. METHODS: Participants completed stress ratings, a cold symptom questionnaire, and exhaled NO measurements at a low-stress period and two periods during their final exams, with one questionnaire follow-up assessment seven days after finals. RESULTS: Beetroot juice was associated with reduced symptoms of cold and sickness during and following finals. Those with asthma showed the greatest benefits. Higher exhaled NO was concurrently and prospectively associated with reduced symptomatology. CONCLUSION: Beetroot juice during periods of psychological stress protects against cold symptoms. Preliminary evidence suggests particular benefits in asthma, which could translate into reduced asthma exacerbations due to respiratory infections. Clinical Trial ID: NCT03159273.

Towards an assessment of perceived COPD exacerbation triggers: Initial development and validation of a questionnaire.

BACKGROUND AND OBJECTIVE: Prevention of exacerbations in chronic obstructive pulmonary disease (COPD) is important to decrease overall declines in functioning and improve quality of life. The present study sought to develop a psychometrically valid measure of perceived triggers of exacerbations in COPD patients, the COPD Exacerbation Trigger Inventory (CETI). METHODS: Participants (n = 192) were recruited through local clinics and online to complete surveys of the CETI, demographic information, disease-specific information and the COPD Assessment Test (CAT). The CETI included a free response section on patients' individual top triggers, combined with ratings of their controllability. RESULTS: Exploratory principal component analyses identified a stable 5-factor structure (33 items), from which trigger subscales for weather/climate, air pollution/irritants, exercise, infection/illness and psychological factors were formed (internal consistency Cronbach's α = 0.90-0.94). Trigger factors were associated with COPD functional status, exacerbation frequency and healthcare utilization. Participants found personal triggers related to dust, air pollution, smoking and physical activity to be the most easily controlled, whereas those related to psychological factors, climate, infection, respiratory symptoms and sleep to be more difficult to control. Greater perceived controllability of triggers was associated with lower CAT scores, indicating better health status and less impact of the disease on functioning. CONCLUSION: The CETI is a psychometrically valid measure of perceived exacerbation triggers in patients with COPD. Perceived triggers are associated with clinical outcomes. Assessment of trigger classes and their controllability may prove useful in both research and clinical settings with COPD patients and to further our knowledge in prevention and disease management.

Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals.

BACKGROUND AND OBJECTIVE: Nitric oxide (NO) plays an important role in the airways' innate immune response, and the fraction of exhaled NO at a flow rate of 50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are linked to loss of bronchoprotective effects in airway challenges and predict symptoms of respiratory infection. While beetroot juice supplements have been proposed to enhance exercise performance by increasing dietary nitrate consumption, few studies have examined the impact of beetroot juice or nitrate supplementation on airway NO in contexts beyond an exercise challenge, which we know influences FENO50. METHODS: We therefore examined the influence of a beetroot juice supplement on FENO50 in healthy males and females (n = 38) during periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure, and state affect were measured at baseline, 45 minutes, and 90 minutes following ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were followed with ingestion of 70ml of water on a control day. RESULTS: After beetroot consumption, average values of the natural log of FENO50 (lnFENO50) increased by 21.3% (Cohen's d = 1.54, p < .001) 45 minutes after consumption and by 20.3% (Cohen's d = 1.45, p < .001) 90 min after consumption. On the other hand, only very small increases in FENO50 were observed after consumption of the control liquid (less than 1% increase). A small subset (n = 4) of participants completed an extended protocol lasting over 3 hours, where elevated levels of FENO50 persisted. No significant changes in cardiovascular measures were observed with this small single dose of beetroot juice. CONCLUSION: As NO serves a key role in innate immunity, future research is needed to explore the potential clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent respiratory infection.

Sensitivity of salivary hydrogen sulfide to psychological stress and its association with exhaled nitric oxide and affect.

BACKGROUND: Hydrogen sulfide (H2S) is the third gasotransmitter recently discovered after nitric oxide (NO) and carbon monoxide. Both NO and H2S are involved in multiple physiological functions. Whereas NO has been shown to vary with psychological stress, the influence of stress on H2S and the relationship between H2S and NO are unknown. We therefore examined levels of salivary H2S and NO in response to a stressful final academic exam period. METHODS: Measurements of stress, negative affect, and fraction of exhaled NO (FENO), were obtained from students (N=16) and saliva was collected at three time points: low-stress period in the semester, early exam period, and late exam period. Saliva was immediately analyzed for H2S with the fluorescent probe Sulfidefluor-4. RESULTS: H2S increased significantly during the early exam period and FENO decreased gradually towards the late exam period. H2S, FENO, negative affect, and stress ratings were positively associated with each other: as stress level and negative affect increased, values of H2S increased; in addition, as FENO levels decreased, H2S also decreased. Asthma status did not modify these associations. CONCLUSION: Sustained academic stress increases H2S and these changes are correlated with NO and the experience of stress and negative affect. These findings motivate research with larger samples to further explore the interaction and function of H2S and FENO during psychological stress.

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1).

Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: 1) weekly baseline measures; 2) a psychosocial speech and mental arithmetic stressor under evaluative threat; and 3) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test-retest reliability estimate = 0.62-0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study.