Good perceived sleep quality protects against the raised risk of respiratory infection during sleep restriction in young adults.

STUDY OBJECTIVES: Prospectively examine the association between sleep restriction, perceived sleep quality (PSQ) and upper respiratory tract infection (URTI). METHODS: In 1318 military recruits (68% males) self-reported sleep was assessed at the beginning and end of a 12-week training course. Sleep restriction was defined as an individualized reduction in sleep duration of ≥2 hours/night compared with civilian life. URTIs were retrieved from medical records. RESULTS: On commencing training, approximately half of recruits were sleep restricted (52%; 2.1 ± 1.6 h); despite the sleep debt, 58% of recruits with sleep restriction reported good PSQ. Regression adjusted for covariates showed that recruits commencing training with sleep restriction were more likely to suffer URTI during the course (OR = 2.93, 95% CI 1.29-6.69, p = .011). Moderation analysis showed this finding was driven by poor PSQ (B = -1.12, SE 0.50, p = .023), as no significant association between sleep restriction and URTI was observed in recruits reporting good PSQ, despite a similar magnitude of sleep restriction during training. Associations remained in the population completing training, accounting for loss to follow-up. Recruits reporting poor PSQ when healthy at the start and end of training were more susceptible to URTI (OR = 3.16, 95% CI 1.31-7.61, p = .010, vs good PSQ). CONCLUSION: Good perceived sleep quality was associated with protection against the raised risk of respiratory infection during sleep restriction. Studies should determine whether improvements in sleep quality arising from behavioral sleep interventions translate to reduced respiratory infection during sleep restriction.

Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.

PURPOSE: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training.

Tear Lactoferrin and Lysozyme as Clinically Relevant Biomarkers of Mucosal Immune Competence.

Tears have attracted interest as a minimally-invasive biological fluid from which to assess biomarkers. Lactoferrin (Lf) and lysozyme (Lys) are abundant in the tear fluid and have antimicrobial properties. Since the eye is a portal for infection transmission, assessment of immune status at the ocular surface may be clinically relevant. Therefore, the aim of this series of studies was to investigate the tear fluid antimicrobial proteins (AMPs) Lf and Lys as biomarkers of mucosal immune status. To be considered biomarkers of interest, we would expect tear AMPs to respond to stressors known to perturb immunity but be robust to confounding variables, and to be lower in participants with heightened risk or incidence of illness. We investigated the relationship between tear AMPs and upper respiratory tract infection (URTI; study 1) as well as the response of tear AMPs to prolonged treadmill exercise (study 2) and dehydration (study 3). Study 1 was a prospective cohort study conducted during the common cold season whereas studies 2 and 3 used repeated-measures crossover designs. In study 1, tear Lys concentration (C) as well as tear AMP secretion rates (SRs) were lower in individuals who reported pathogen-confirmed URTI (n = 9) throughout the observation period than in healthy, pathogen-free controls (n = 17; Lys-C, P = 0.002, d = 0.85; Lys-SR, P < 0.001, d = 1.00; Lf-SR, P = 0.018, d = 0.66). Tear AMP secretion rates were also lower in contact lens wearers. In study 2, tear AMP SRs were 42-49% lower at 30 min-1 h post-exercise vs. pre-exercise (P < 0.001, d = 0.80-0.93). Finally, in study 3, tear AMPs were not influenced by dehydration, although tear AMP concentrations (but not secretion rates) displayed diurnal variation. We conclude that Lf and Lys have potential as biomarkers of mucosal immune competence; in particular, whether these markers are lower in infection-prone individuals warrants further investigation.

Anxiety and perceived psychological stress play an important role in the immune response after exercise.

There are common pathways by which psychological stress and exercise stress alter immunity. However, it remains unknown whether psychological stress plays a role in the in vivo immune response to exercise. We examined the relationship between anxiety and perceived psychological stress reported before exercise and in vivo immunity after exercise using skin sensitisation with Diphenylcyclopropenone (DPCP). In a randomised design, sixty four, thoroughly familiarised, males completed widely used psychological instruments to assess state-anxiety and perceived psychological stress before exercise, and ran either 30 minutes at 60% (30MI) or 80% (30HI) V . O2peak, 120 minutes at 60% (120MI) V . O2peak or rested (CON) before DPCP sensitisation. Cutaneous recall to DPCP was measured as the dermal thickening response to a low-dose series DPCP challenge 4-weeks after sensitisation. After accounting for exercise (R2 = 0.20; P < 0.01), multiple-regression showed that pre-exercise state-anxiety (STAI-S; ΔR2 = 0.19; P < 0.01) and perceived psychological stress (ΔR2 = 0.13; P < 0.05) were moderately associated with the DPCP response after exercise. The STAI-S scores before exercise were considered low-to-moderate in these familiarised individuals (median split; mean STAI-S of low 25 and moderate 34). Further examination showed that the DPCP response after exercise (30MI, 30HI or 120MI) was 62% lower in those reporting low vs. moderate state-anxiety before exercise (mean difference in dermal thickening: -2.6 mm; 95% CI: -0.8 to -4.4 mm; P < 0.01). As such, the results indicate a beneficial effect of moderate (vs. low) state-anxiety and perceived psychological stress on in vivo immunity after exercise. Moreover, correlations were of comparable strength for the relationship between physiological stress (heart rate training impulse) and the summed dermal response to DPCP (r = -0.37; 95% CI: -0.05 to -0.62; P = 0.01), and state-anxiety and the summed dermal response to DPCP (r = 0.39; 95% CI: 0.08 to 0.63; P < 0.01). In conclusion, state-anxiety and perceived psychological stress levels before exercise play animportant role in determining the strength of the in vivo immune response after exercise. These findings indicate a similar strength relationship for the level of state-anxiety prior to exercise and the level of physiological stress during exercise with the in vivo immune response after exercise. Future research is required to investigate exercise-immune responses in athletes, military personnel and others in physically demanding occupations experiencing higher levels of psychological stress than those reported in this study e.g. related to important competition, military operations and major life events. Nevertheless, the present findings support the recommendation that exercise scientists should account for anxiety and psychological stress when examining the immune response to exercise.

High heart rate reactors display greater decreases in tear SIgA concentration following a novel acute stressor.

Tear secretory immunoglobulin-A (SIgA) is a putative biomarker of common-cold risk with potential utility in non-invasive diagnostics. As SIgA secretion at the ocular surface is under strong autonomic control, we investigated the relationship between HR reactivity and tear SIgA responses to novel experiential stress. Thirty-two healthy participants undertook a 60 s zip-line ride to evoke acute stress and a seated-rest control trial in a randomised-crossover design. We recorded heart rate (HR) continuously and collected unstimulated tear samples 5 min pre-, 2 min post- and 20 min post-stress/control. Stress increased HR and state anxiety whereas tear SIgA concentration decreased 44% post-stress vs. CONTROL: Higher peak HR values during stress uniquely explained 21% of the variance in tear SIgA reactivity to stress (p < 0.01); high HR reactors displayed greater decreases in tear SIgA concentration. We conclude that physiological arousal increases immune reactivity to acute stress and highlight tear SIgA as a minimally-invasive, physiologically relevant biomarker of immune reactivity.

Tear Fluid SIgA as a Noninvasive Biomarker of Mucosal Immunity and Common Cold Risk.

PURPOSE: Research has not convincingly demonstrated the utility of saliva secretory immunoglobulin-A (SIgA) as a biomarker of upper respiratory tract infection (URTI) risk, and disagreement exists about the influence of heavy exercise ("open-window theory") and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study 1) and assessed the influence of exercise (study 2) and dehydration (study 3) using a repeated-measures crossover design. METHODS: In study 1, 40 subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper respiratory symptoms (URS) daily for 3 wk. Real-time PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected during the week before URS. In study 2, 13 subjects performed a 2-h run at 65% V˙O2peak. In study 3, 13 subjects performed exercise heat stress to 3% body mass loss followed by overnight fluid restriction. RESULTS: Tear SIgA concentration and secretion rate were 48% and 51% lower, respectively, during URTI and 34% and 46% lower the week before URS (P < 0.05), but saliva SIgA remained unchanged. The risk of URS the following week increased ninefold (95% confidence interval, 1.7-48) when the tear SIgA secretion rate was <5.5 µg·min(-1) and sixfold (95% confidence interval, 1.2-29) when the tear SIgA secretion rate decreased >30%. Tear SIgA secretion rate >5.5 µg·min(-1) or no decrease of >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased after exercise (-57%, P < 0.05) in line with the "open-window theory" but was unaffected by dehydration. Saliva flow rate decreased and saliva SIgA concentration increased after exercise and during dehydration (P < 0.05). CONCLUSIONS: Tear SIgA has utility as a noninvasive biomarker of mucosal immunity and common-cold risk.

Exercise Intensity and Duration Effects on In Vivo Immunity.

PURPOSE: To examine the effects of intensity and duration of exercise stress on induction of in vivo immunity in humans using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: Sixty-four healthy males completed either 30 min running at 60% V˙O2peak (30MI), 30 min running at 80% V˙O2peak (30HI), 120 min running at 60% V˙O2peak (120MI), or seated rest (CON). Twenty min later, the subjects received a sensitizing dose of DPCP; and 4 wk later, the strength of immune reactivity was quantified by measuring the cutaneous responses to a low dose-series challenge with DPCP on the upper inner arm. Circulating epinephrine, norepinephrine and cortisol were measured before, after, and 1 h after exercise or CON. Next, to understand better whether the decrease in CHS response on 120MI was due to local inflammatory or T-cell-mediated processes, in a crossover design, 11 healthy males performed 120MI and CON, and cutaneous responses to a dose series of the irritant, croton oil (CO), were assessed on the upper inner arm. RESULTS: Immune induction by DPCP was impaired by 120MI (skinfold thickness -67% vs CON; P < 0.05). However, immune induction was unaffected by 30MI and 30HI despite elevated circulating catecholamines (30HI vs pre: P < 0.01) and greater circulating cortisol post 30HI (vs CON; P < 0.01). There was no effect of 120MI on skin irritant responses to CO. CONCLUSIONS: Prolonged moderate-intensity exercise, but not short-lasting high- or short-lasting moderate-intensity exercise, decreases the induction of in vivo immunity. No effect of prolonged moderate-intensity exercise on the skin's response to irritant challenge points toward a suppression of cell-mediated immunity in the observed decrease in CHS. Diphenylcyclopropenone provides an attractive tool to assess the effect of exercise on in vivo immunity.