Metabolic Phenotyping from Whole-Blood Responses to a Standardized Exercise Test May Discriminate for Physiological, Performance, and Illness Outcomes: A Pilot Study in Highly-Trained Cross-Country Skiers.

BACKGROUND: This study used metabolic phenotyping to explore the responses of highly-trained cross-country skiers to a standardized exercise test, which was part of the athletes' routine testing, and determine whether metabolic phenotyping could discriminate specific physiological, performance, and illness characteristics. METHODS: Twenty-three highly-trained cross-country skiers (10 women and 13 men) participated in this study. Capillary whole-blood samples were collected before (at rest) and 2.5 min after (post-exercise) a roller-ski treadmill test consisting of 5-6 × 4-min submaximal stages followed by a self-paced time trial (~ 3 min) and analyzed using mass spectrometry. Performance level was defined by International Ski Federation distance and sprint rankings. Illness data were collected prospectively for 33 weeks using the Oslo Sports Trauma Research Center Questionnaire on Health Problems. Orthogonal partial least squares-discriminant analyses (OPLS-DA) followed by enrichment analyses were used to identify metabolic phenotypes of athlete groups with specific physiological, performance, and illness characteristics. RESULTS: Blood metabolite phenotypes were significantly different after the standardized exercise test compared to rest for metabolites involved in energy, purine, and nucleotide metabolism (all OPLS-DA p < 0.001). Acute changes in the metabolic phenotype from rest to post-exercise could discriminate athletes with: (1) higher vs. lower peak blood lactate concentrations; (2) superior vs. inferior performance levels in sprint skiing, and (3) ≥ 2 vs. ≤ 1 self-reported illness episodes in the 33-week study period (all p < 0.05). The most important metabolites contributing to the distinction of groups according to (1) post-exercise blood lactate concentrations, (2) sprint performance, and (3) illness frequency were: (1) inosine, hypoxanthine, and deoxycholic acid, (2) sorbitol, adenosine monophosphate, and 2-hydroxyleuroylcarnitine, and (3) glucose-6-phosphate, squalene, and deoxycholic acid, respectively. CONCLUSION: Metabolic phenotyping discriminated between athlete groups with higher vs. lower post-exercise blood lactate concentrations, superior vs. inferior sprint skiing performance, and more vs. less self-reported illnesses. While the biological relevance of the identified biomarkers requires validation in future research, metabolic phenotyping shows promise as a tool for routine monitoring of highly-trained endurance athletes.

Hypoxic pulmonary vasoconstriction does not limit maximal exercise capacity in healthy volunteers breathing 12% oxygen at sea level.

Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.

Elite skiers' experiences of heat- and moisture-exchanging devices and training and competition in the cold: A qualitative survey.

Background and Aims: Winter endurance athletes have a high prevalence of exercise-induced bronchoconstriction (EIB) and asthma, probably due to repeated and prolonged inhalation of cold and dry air. Heat- and moisture-exchanging devices (HME) warm and humidify inhaled air and prevent EIB. The aim of this study was to share cross-country skiers and biathletes' experiences of training and competition in low temperatures, views on temperature limits, usage of HME, and consequences of cold exposure on their health. Methods: Eleven Swedish World Championship or Olympic medalists in cross-country skiing and biathlon were interviewed and transcripts were analyzed using qualitative content analysis. Results: Participants described how cold temperatures predominantly affected the airways, face, and extremities. During training, extreme cold was managed by choosing warmer clothing, modification of planned sessions, use of HME, delaying training, or changing location. In competition, participants described limited possibility for such choices and would prefer adjustment of existing rules (i.e., more conservative temperature limits), especially since they understood elite skiing in low temperatures to present an occupational hazard to their health. Participants had at times used HMEs during training in cold environments but described mixed motives for their use-that HMEs warm and humidify cold inhaled air but introduce additional resistance to breathing and can cause problems due to mucus and ice build-up. Skiers also perceived that they had become more sensitive to cold during the latter part of their careers. Conclusions: The present study gives a unique insight into the "cold" reality of being an elite athlete in skiing and biathlon. Cold exposure results in negative health consequences that are preventable, which means that rules must be followed, and organizers should acknowledge responsibility in protecting athletes from occupational hazards. Development of evidence-based guidelines for protection of athletes' respiratory health should be a focus for future translational research.

A post-exercise infrared sauna session improves recovery of neuromuscular performance and muscle soreness after resistance exercise training.

The aim of this study was to investigate effects of a single infrared sauna (IRS) session on post-exercise recovery of neuromuscular performance, autonomic nervous system function, subjective sleep quality, and muscle soreness. Male basketball players (n = 16) performed two trials consisting of a complex resistance exercise protocol (maximal strength with plyometrics), followed by either 20 min passive recovery (PAS) or IRS (temperature 43 ± 5°C), in a randomized crossover design, with trials separated by one week. Recovery of neuromuscular performance was assessed using 20 m maximal sprint, maximal countermovement-jump (CMJ), and isometric leg press tests, performed 14 hours after exercise. Heart rate (HR), heart rate variability (HRV), sleep diary, muscle soreness, and indirect muscle damage markers were measured pre and post exercise. The decrease in CMJ performance from pre- to post-exercise was attenuated after IRS compared to PAS (p < 0.01). The IRS session resulted in higher HR and lower root mean square of successive differences between normal heartbeats (RMSSD), and high and low frequency power, compared to PAS (p < 0.002). Post-exercise night-time HR and HRV did not differ following IRS vs. PAS. Muscle soreness was less severe, and perceived recovery was higher after IRS compared to PAS (p < 0.01). Post-exercise IRS attenuated the drop in explosive performance and decreased subjective muscle soreness after resistance training, which may enhance mood, readiness, and physical performance of an athlete. A single IRS session had no detrimental effects on recovery of the autonomic nervous system.

Nocturnal Heart Rate Variability in Women Discordant for Hormonal Contraceptive Use.

PURPOSE: The aim of this study was to investigate within-cycle differences in nocturnal heart rate (HR) and heart rate variability (HRV) in naturally menstruating women (NM) and women using combined hormonal contraceptives (CU) or progestin-only hormonal contraceptives (PU). METHODS: Physically active participants were recruited into three groups: NM ( n = 19), CU ( n = 11), and PU ( n = 12). Participants' HR and HRV (with Bodyguard 2 HRV monitor) and blood hormones were monitored during one menstrual cycle (MC) (NM group) or for 4 wk (CU and PU groups). Estradiol, progesterone, and luteinizing hormone were analyzed from fasting blood samples collected four times in the NM (M1 = bleeding, M2 = follicular phase, M3 = ovulation, and M4 = luteal phase) and PU groups (M1 = lowest E 2 , M2 = M1 + 7 d, M3 = M1 + 14 d, and M4 = M1 + 21 d) and twice in the CU group (active and inactive pill phases). After every blood sample, nightly HR and HRV were recorded and examined as an average from two nights. RESULTS: Hormonal concentrations differed ( P < 0.05) between MC phases in the NM and PU groups, but not ( P ≥ 0.116) between the active and the inactive phases in the CU group. In the NM and PU groups, some of the HRV values were higher, whereas in the NM group, HR was lower during M2 compared with M3 ( P < 0.049) and M4 ( P < 0.035). In the CU group, HRV values ( P = 0.014-0.038) were higher, and HR was lower ( P = 0.038) in the inactive phase compared with the first week of the active phase. CONCLUSIONS: The MC and the hormonal cycle phases influence autonomic nervous system balance, which is reflected in measurements of nocturnal HR and HRV. This should be considered when monitoring recovery in physically active individuals.

Cold air exposure at - 15 °C induces more airway symptoms and epithelial stress during heavy exercise than rest without aggravated airway constriction.

PURPOSE: Exposure to cold air may harm the airways. It is unclear to what extent heavy exercise adds to the cold-induced effects on peripheral airways, airway epithelium, and systemic immunity among healthy individuals. We investigated acute effects of heavy exercise in sub-zero temperatures on the healthy airways. METHODS: Twenty-nine healthy individuals underwent whole body exposures to cold air in an environmental chamber at - 15 °C for 50 min on two occasions; a 35-min exercise protocol consisting of a 5-min warm-up followed by 2 × 15 min of running at 85% of VO2max vs. 50 min at rest. Lung function was measured by impulse oscillometry (IOS) and spirometry before and immediately after exposures. CC16 in plasma and urine, and cytokines in plasma were measured before and 60 min after exposures. Symptoms were surveyed pre-, during and post-trials. RESULTS: FEV1 decreased after rest (- 0.10 ± 0.03 L, p < 0.001) and after exercise (- 0.06 ± 0.02 L, p = 0.012), with no difference between trials. Exercise in - 15 °C induced greater increases in lung reactance (X5; p = 0.023), plasma CC16 (p < 0.001) as well as plasma IL-8 (p < 0.001), compared to rest. Exercise induced more intense symptoms from the lower airways, whereas rest gave rise to more general symptoms. CONCLUSION: Heavy exercise during cold air exposure at - 15 °C induced signs of an airway constriction to a similar extent as rest in the same environment. However, biochemical signs of airway epithelial stress, cytokine responses, and symptoms from the lower airways were more pronounced after the exercise trial.

Influence of exercise duration on respiratory function and systemic immunity among healthy, endurance-trained participants exercising in sub-zero conditions.

BACKGROUND: Strenuous endurance exercise in sub-zero temperatures can cause airway damage that may lead to EIB. Prolonged exercise can also elicit greater immune perturbations than short-duration exercise. However, the influence of exercise duration on lung function and systemic immunity in sub-zero temperatures has not been established. Additionally, it is currently unknown whether atopic disposition, which is risk factor for EIB, influences respiratory responses in a sub-zero climate. The aim of this study was to compare respiratory and systemic immune responses to two cold air running trials of short and long duration, as well as to examine whether the responses differed between atopic and non-atopic subjects. METHODS: Eighteen healthy, endurance-trained subjects (males/females: 14/4; age: 29.4 ± 5.9 years old; BMI: 23.1 ± 1.7; atopic/non-atopic: 10/8) completed two moderate-intensity climate chamber running trials at - 15 °C, lasting 30 and 90 min, in a randomized, cross-over design. Lung function (spirometry and impulse oscillometry), serum CC16, respiratory symptoms, and blood leukocyte counts were examined before and after the trials. RESULTS: Lung function was not significantly affected by exercise or exercise duration. CC16 concentration increased after both trials (p = 0.027), but the response did not differ between trials. Respiratory symptom intensity was similar after each trial. There was a greater increase in neutrophils (p < 0.001), and a decrease in eosinophils (p < 0.001) after the 90-min bout. The 90-min protocol increased X5 compared to the 30-min protocol only in atopic subjects (p = 0.015) while atopy increased lower airway symptoms immediately after the 90-min session (p = 0.004). CONCLUSIONS: Our results suggest that a 90-min bout of moderate-intensity exercise at - 15 °C does not cause substantial lung function decrements, airway epithelial damage or respiratory symptoms compared to 30 min running in the same environment, despite a heightened redistribution of white blood cells. However, exercise at - 15 °C may cause airway injury and evoke respiratory symptoms, even at moderate intensity. Atopic status may lead to greater peripheral bronchodilation and higher frequency of respiratory symptoms after long-duration exercise in cold. TRIAL REGISTRATION: 01/02/2022 ISRCTN13977758. This trial was retrospectively registered upon submission to satisfy journal guidelines. The authors had not initially registered the study, as the intervention was considered to be a controlled simulation of exercise in a naturally occurring environment (i.e. sub-zero air) for healthy volunteers.

A breathing mask attenuates acute airway responses to exercise in sub-zero environment in healthy subjects.

PURPOSE: Cold air exposure is associated with increased respiratory morbidity and mortality. Repeated inhalation of cold and dry air is considered the cause of the high prevalence of asthma among winter endurance athletes. This study assessed whether a heat- and moisture-exchanging breathing device (HME) attenuates airway responses to high-intensity exercise in sub-zero temperatures among healthy subjects. METHODS: Using a randomized cross-over design, 23 healthy trained participants performed a 30-min warm-up followed by a 4-min maximal, self-paced running time trial in - 15 °C, with and without HME. Lung function was assessed pre- and immediately post-trials. Club cell protein (CC-16), 8-isoprostane, and cytokine concentrations were measured in plasma and urine pre- and 60 min post trials. Symptoms were assessed prior to, during, and immediately after each trial in the chamber. RESULTS: HME use attenuated the decrease in forced expiratory volume in 1 s (FEV1) post trials (∆FEV1: mean (SD) HME - 0.5 (1.9) % vs. no-HME - 2.7 (2.7) %, p = 0.002). HME also substantially attenuated the median relative increase in plasma-CC16 concentrations (with HME + 27% (interquartile range 9-38) vs no-HME + 121% (55-162), p < 0.001) and reduced airway and general symptom intensity, compared to the trial without HME. No significant changes between trials were detected in urine CC16, 8-isoprostane, or cytokine concentrations. CONCLUSION: The HME attenuated acute airway responses induced by moderate-to-maximal-intensity exercise in - 15 °C in healthy subjects. Further studies are needed to examine whether this HMEs could constitute primary prevention against asthma in winter endurance athletes.

Illness Incidence, Psychological Characteristics, and Sleep in Dogsled Drivers During the Iditarod Trail Sled Dog Race.

INTRODUCTION: Every March, dogsled drivers (mushers) compete in a 1569-km race across Alaska, involving physical exertion, mental exertion, and sleep deprivation for up to 2 wk. These factors may increase mushers' vulnerability to illness, making them a relevant study population for acute infection risk factors. Specifically, the influence of psychological factors on illness risk during prolonged physical exertion has rarely been investigated. The aim of this study was to examine the relationship between psychological characteristics, sleep deprivation, and illness incidence in Iditarod mushers. METHODS: Fourteen mushers completed 4 psychological instruments to assess state and trait anxiety, resilience and perceived stress, and self-reported upper respiratory symptoms (URS) in the month before the race. Mushers self-reported sleep duration and URS during the race. RESULTS: State and trait anxiety, resilience, and perceived stress did not differ between mushers with and without pre- and in-race URS (P>0.05). However, all mushers who reported in-race URS had reported URS ≤9 d before the race, and the onset of symptoms during the race typically occurred shortly after a rest period. Sleep duration was higher in mushers who reported in-race URS, both before (4.9±0.3 h, P=0.016) and during illness (5.9±1.3 h, P=0.006), vs mushers without in-race URS (3.4±0.8 h). CONCLUSIONS: This study highlights recent illness, rest periods, and greater sleep requirements as potential risk factors for URS onset during a multiday endurance challenge, whereas psychological factors were not associated with URS.

Highlights of the ERS Lung Science Conference 2022.

This article presents the highlights of the ERS Lung Science Conference 2022, including a session organised by the Early Career Member Committee (ECMC) dedicated to career development https://bit.ly/3tarCXc.

Acute Exposure to Normobaric Hypoxia Impairs Balance Performance in Sub-elite but Not Elite Basketball Players.

Although high and simulated altitude training has become an increasingly popular training method, no study has investigated the influence of acute hypoxic exposure on balance in team-sport athletes. Therefore, the purpose of this study was to investigate whether acute exposure to normobaric hypoxia is detrimental to balance performance in highly-trained basketball players. Nine elite and nine sub-elite male basketball players participated in a randomized, single-blinded, cross-over study. Subjects performed repeated trials of a single-leg balance test (SLBT) in an altitude chamber in normoxia (NOR; approximately sea level) with FiO2 20.9% and PiO2 ranging from 146.7 to 150.4 mmHg and in normobaric hypoxia (HYP; ~3,800 m above sea level) with FiO2 13.0% and PiO2 ranging from 90.9 to 94.6 mmHg. The SLBT was performed three times: 15 min after entering the environmental chamber in NOR or HYP, then two times more interspersed by 3-min rest. Peripheral oxygen saturation (SpO2) and heart rate (HR) were recorded at four time points: after the initial 15-min rest inside the chamber and immediately after each SLBT. Across the cohort, the balance performance was 7.1% better during NOR than HYP (P < 0.01, η p 2 = 0.58). However, the performance of the elite group was not impaired by HYP, whereas the sub-elite group performed worse in the HYP condition on both legs (DL: P = 0.02, d = 1.23; NDL: P = 0.01, d = 1.43). SpO2 was lower in HYP than NOR (P < 0.001, η p 2 = 0.99) with a significant decline over time during HYP. HR was higher in HYP than NOR (P = 0.04, η p 2 = 0.25) with a significant increase over time. Acute exposure to normobaric hypoxia detrimentally affected the balance performance in sub-elite but not elite basketball players.

An experimental exposure study revealing composite airway effects of physical exercise in a subzero environment.

Exposure to a cold climate is associated with an increased morbidity and mortality, but the specific mechanisms are largely unknown. People with cardiopulmonary disease and winter endurance athletes are particularly vulnerable. This study aimed to map multiple domains of airway responses to exercise in subzero temperature in healthy individuals.Thirty-one healthy subjects underwent whole-body exposures for 50 minutes on two occasions in an environmental chamber with intermittent moderate-intensity exercise in +10 °C and -10 °C. Lung function, plasma/urine CC16 , and symptoms were investigated before and after exposures.Compared to baseline, exercise in -10 °C decreased FEV1 (p=0.002), FEV1/FVC (p<0.001), and increased R20Hz (p=0.016), with no differences between exposures. Reactance increased after +10 °C (p=0.005), which differed (p=0.042) from a blunted response after exercise in -10 °C. Plasma CC16 increased significantly within exposures, without differences between exposures. Exercise in -10 °C elicited more intense symptoms from the upper airways, compared to +10 °C. Symptoms from the lower airways were few and mild. Short-duration moderate-intensity exercise in -10 °C induces mild symptoms from the lower airways, no lung function decrements or enhanced leakage of biomarkers of airway epithelial injury, and no peripheral bronchodilatation, compared to exercise in +10 °C.

A heat and moisture-exchanging mask impairs self-paced maximal running performance in a sub-zero environment.

PURPOSE: Heat-and-moisture-exchanging devices (HME) are commonly used by endurance athletes during training in sub-zero environments, but their effects on performance are unknown. We investigated the influence of HME usage on running performance at - 15 °C. METHODS: Twenty-three healthy adults (15 male, 8 female; age 18-53 years; [Formula: see text] men 56 ± 7, women 50 ± 4 mL·kg-1·min-1) performed two treadmill exercise tests with and without a mask-style HME in a randomised, crossover design. Participants performed a 30-min submaximal warm-up (SUB), followed by a 4-min maximal, self-paced running time-trial (TT). Heart rate (HR), respiratory frequency (fR), and thoracic area skin temperature (Tsk) were monitored using a chest-strap device; muscle oxygenation (SmO2) and deoxyhaemoglobin concentration ([HHb]) were derived from near-infra-red-spectroscopy sensors on m. vastus lateralis; blood lactate was measured 2 min before and after the TT. RESULTS: HME usage reduced distance covered in the TT by 1.4%, despite similar perceived exertion, HR, fR, and lactate accumulation. The magnitude of the negative effect of the HME on performance was positively associated with body mass (r2 = 0.22). SmO2 and [HHb] were 3.1% lower and 0.35 arb. unit higher, respectively, during the TT with HME, and Tsk was 0.66 °C higher during the HME TT in men. HR (+ 2.7 beats·min-1) and Tsk (+ 0.34 °C) were higher during SUB with HME. In the male participants, SmO2 was 3.8% lower and [HHb] 0.42 arb. unit higher during SUB with HME. CONCLUSION: Our findings suggest that HME usage impairs maximal running performance and increases the physiological demands of submaximal exercise.

Exercise in Sub-zero Temperatures and Airway Health: Implications for Athletes With Special Focus on Heat-and-Moisture-Exchanging Breathing Devices.

Asthma is highly prevalent among winter endurance athletes. This "occupational disease" of cross-country skiers, among others, was acknowledged during the 1990s, with the pathogenesis attributed to repeated and prolonged exposure to cold, dry air combined with high rates of ventilation during exercise. Nevertheless, more than 25 years later, the prevalence of asthma among Scandinavian cross-country skiers is unchanged, and prevention remains a primary concern for sports physicians. Heat-and-moisture-exchanging breathing devices (HMEs) prevent exercise-induced bronchoconstriction in subjects with pre-existing disease and may have potential as a preventative intervention for healthy athletes undertaking training and competition in winter endurance sports. Herein we firstly provide an overview of the influence of temperature and humidity on airway health and the implications for athletes training and competing in sub-zero temperatures. We thereafter describe the properties and effects of HMEs, identify gaps in current understanding, and suggest avenues for future research.

Influence of Immune and Nutritional Biomarkers on Illness Risk During Interval Training.

Intensive training periods may negatively influence immune function, but the immunological consequences of specific high-intensity-training (HIT) prescriptions are not well defined. PURPOSE: To explore whether 3 different HIT prescriptions influence multiple health-related biomarkers and whether biomarker responses to HIT were associated with upper-respiratory-illness (URI) risk. METHODS: Twenty-five male cyclists and triathletes were randomized to 3 HIT groups and completed 12 HIT sessions over 4 wk. Peak oxygen consumption (V˙O2peak) was determined using an incremental cycling protocol, while resting serum biomarkers (cortisol, testosterone, 25[OH]D, and ferritin), salivary immunoglobulin-A (s-IgA), and energy availability (EA) were assessed before and after the training intervention. Participants self-reported upper-respiratory symptoms during the intervention, and episodes of URI were identified retrospectively. RESULTS: Fourteen athletes reported URIs, but there were no differences in incidence, duration, or severity between groups. Increased risk of URI was associated with higher s-IgA secretion rates (odds ratio = 0.90, 90% confidence interval 0.83-0.97). Lower preintervention cortisol and higher EA predicted a 4% increase in URI duration. Participants with higher V˙O2peak reported higher total symptom scores (incidence rate ratio = 1.07, 90% confidence interval 1.01-1.13). CONCLUSIONS: Although multiple biomarkers were weakly associated with risk of URI, the direction of associations between s-IgA, cortisol, EA, and URI risk were inverse to previous observations and physiological rationale. There was a cluster of URIs in the first week of the training intervention, but no samples were collected at this time point. Future studies should incorporate more-frequent sample time points, especially around the onset of new training regimens, and include athletes with suspected or known nutritional deficiencies.

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.

Qualitative identification and characterisation of self-reported symptoms arising in humans during experimental exposure to cold air.

BACKGROUND: Exposure to cold air is associated with increased morbidity and mortality in the general population. It is difficult to study the effects of whole-body exposure to cold air under controlled conditions in real life. OBJECTIVES: The aim of this study was to (1) explore and describe the experience of symptoms in humans during experimental and controlled exposures to cold air, by using controlled environmental chamber exposures and qualitative methodology, and to (2) categorise the symptoms. METHOD: The study used a randomised, double blind design, in which 34 subjects undertook rest and moderate-intensity exercise in an environmental chamber set to two or three different temperatures (0, -10, and -17°C) on separate occasions. During the chamber exposures, subjects were interviewed. Qualitative content analysis was selected as the method of analysis. FINDINGS: Subjects reported 50 distinct symptoms during the exposures. The symptoms were grouped into ten sub-categories and two major categories; airway versus whole-body symptoms. CONCLUSION: We have identified a broad range of symptoms in humans undertaking rest and moderate-intensity exercise at sub-zero temperatures. The symptoms and their categories may well be used to more extensively and quantitatively map cold-induced morbidity.

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.