Matthew B. Fortes

Tear Fluid Osmolarity as a Potential Marker of Hydration Status

UNLABELLED It has been suggested that tear fluid is isotonic with plasma, and plasma osmolality (P(osm)) is an accepted, albeit invasive, hydration marker. Our aim was to determine whether tear fluid osmolarity (T(osm)) assessed using a new, portable, noninvasive, rapid collection and measurement device tracks hydration. PURPOSE This study aimed to compare changes in T(osm) and another widely used noninvasive marker, urine specific gravity (USG), with changes in P(osm) during hypertonic-hypovolemia. METHODS In a randomized order, 14 healthy volunteers exercised in the heat on one occasion with fluid restriction (FR) until 1%, 2%, and 3% body mass loss (BML) and with overnight fluid restriction until 08:00 h the following day, and on another occasion with fluid intake (FI). Volunteers were rehydrated between 08:00 and 11:00 h. T(osm) was assessed using the TearLab osmolarity system. RESULTS P(osm) and USG increased with progressive dehydration on FR (P < 0.001). T(osm) increased significantly on FR from 293 ± 9 to 305 ± 13 mOsm·L(-1) at 3% BML and remained elevated overnight (304 ± 14 mOsm·L(-1); P < 0.001). P(osm) and T(osm) decreased during exercise on FI and returned to preexercise values the following morning. Rehydration restored P(osm), USG, and T(osm) to within preexercise values. The mean correlation between T(osm) and P(osm) was r = 0.93 and that between USG and P(osm) was r = 0.72. CONCLUSIONS T(osm) increased with dehydration and tracked alterations in P(osm) with comparable utility to USG. Measuring T(osm) using the TearLab osmolarity system may offer sports medicine practitioners, clinicians, and research investigators a practical and rapid hydration assessment technique.

Is This Elderly Patient Dehydrated? Diagnostic Accuracy of Hydration Assessment Using Physical Signs, Urine, and Saliva Markers

OBJECTIVES Dehydration in older adults contributes to increased morbidity and mortality during hospitalization. As such, early diagnosis of dehydration may improve patient outcome and reduce the burden on healthcare. This prospective study investigated the diagnostic accuracy of routinely used physical signs, and noninvasive markers of hydration in urine and saliva. DESIGN Prospective diagnostic accuracy study. SETTING Hospital acute medical care unit and emergency department. PARTICIPANTS One hundred thirty older adults [59 males, 71 females, mean (standard deviation) age = 78 (9) years]. MEASUREMENTS Participants with any primary diagnosis underwent a hydration assessment within 30 minutes of admittance to hospital. Hydration assessment comprised 7 physical signs of dehydration [tachycardia (>100 bpm), low systolic blood pressure (<100 mm Hg), dry mucous membrane, dry axilla, poor skin turgor, sunken eyes, and long capillary refill time (>2 seconds)], urine color, urine specific gravity, saliva flow rate, and saliva osmolality. Plasma osmolality and the blood urea nitrogen to creatinine ratio were assessed as reference standards of hydration with 21% of participants classified with water-loss dehydration (plasma osmolality >295 mOsm/kg), 19% classified with water-and-solute-loss dehydration (blood urea nitrogen to creatinine ratio >20), and 60% classified as euhydrated. RESULTS All physical signs showed poor sensitivity (0%-44%) for detecting either form of dehydration, with only low systolic blood pressure demonstrating potential utility for aiding the diagnosis of water-and-solute-loss dehydration [diagnostic odds ratio (OR) = 14.7]. Neither urine color, urine specific gravity, nor saliva flow rate could discriminate hydration status (area under the receiver operating characteristic curve = 0.49-0.57, P > .05). In contrast, saliva osmolality demonstrated moderate diagnostic accuracy (area under the receiver operating characteristic curve = 0.76, P < .001) to distinguish both dehydration types (70% sensitivity, 68% specificity, OR = 5.0 (95% confidence interval 1.7-15.1) for water-loss dehydration, and 78% sensitivity, 72% specificity, OR = 8.9 (95% confidence interval 2.5-30.7) for water-and-solute-loss dehydration). CONCLUSIONS With the exception of low systolic blood pressure, which could aid in the specific diagnosis of water-and-solute-loss dehydration, physical signs and urine markers show little utility to determine if an elderly patient is dehydrated. Saliva osmolality demonstrated superior diagnostic accuracy compared with physical signs and urine markers, and may have utility for the assessment of both water-loss and water-and-solute-loss dehydration in older individuals. It is particularly noteworthy that saliva osmolality was able to detect water-and-solute-loss dehydration, for which a measurement of plasma osmolality would have no diagnostic utility.

Dehydration decreases saliva antimicrobial proteins important for mucosal immunity.

The aim of the study was to investigate the effect of exercise-induced dehydration and subsequent overnight fluid restriction on saliva antimicrobial proteins important for host defence (secretory IgA (SIgA), α-amylase, and lysozyme). On two randomized occasions, 13 participants exercised in the heat, either without fluid intake to evoke progressive body mass losses (BML) of 1%, 2%, and 3% with subsequent overnight fluid restriction until 0800 h in the following morning (DEH) or with fluids to offset losses (CON). Participants in the DEH trial rehydrated from 0800 h until 1100 h on day 2. BML, plasma osmolality (Posm), and urine specific gravity (USG) were assessed as hydration indices. Unstimulated saliva samples were assessed for flow rate (SFR), SIgA, α-amylase, and lysozyme concentrations. Posm and USG increased during dehydration and remained elevated after overnight fluid restriction (BML = 3.5% ± 0.3%, Posm = 297 ± 6 mosmol·kg⁻¹, and USG = 1.026 ± 0.002; P < 0.001). Dehydration decreased SFR (67% at 3% BML, 70% at 0800 h; P < 0.01) and increased SIgA concentration, with no effect on SIgA secretion rate. SFR and SIgA responses remained unchanged in the CON trial. Dehydration did not affect α-amylase or lysozyme concentration but decreased secretion rates of α-amylase (44% at 3% BML, 78% at 0800 h; P < 0.01) and lysozyme (46% at 3% BML, 61% at 0800 h; P < 0.01), which were lower than in CON at these time points (P < 0.05). Rehydration returned all saliva variables to baseline. In conclusion, modest dehydration (~3% BML) decreased SFR, α-amylase, and lysozyme secretion rates. Whether the observed magnitude of decrease in saliva AMPs during dehydration compromises host defence remains to be shown.

Exercising in a hot environment with muscle damage: Effects on acute kidney injury biomarkers and kidney function

Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin-6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r = 0.9, P = 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments.

Muscle-Damaging Exercise Increases Heat Strain during Subsequent Exercise Heat Stress

PURPOSE It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of exertional heat illness. We examined heat strain during exercise heat stress 30 min after EIMD to coincide with increases in circulating pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure (M˙) and thus decreased economy might also increase heat strain. METHODS Thirteen non-heat-acclimated males (mean ± SD, age = 20 ± 2 yr) performed exercise heat stress tests (running for 40 min at 65% V˙O2max in 33°C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving running for 60 min at 65% V˙O2max on either -10% gradient (EIMD) or +1% gradient (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate, and M˙ were measured throughout HS tests. RESULTS Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P < 0.01). The ΔTre was greater after EIMD than CON during HS1 (0.35°C, 95% confidence interval = 0.11°C-0.58°C, P < 0.01) and HS2 (0.17°C, 95% confidence interval = 0.07°C-0.28°C, P < 0.01). M˙ was higher on EIMD throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r = 0.67). CONCLUSIONS Heat strain was increased during endurance exercise in the heat conducted 30 min after and, to a much lesser extent, 24 h after muscle-damaging exercise. These data indicate that EIMD is a likely risk factor for exertional heat illness particularly during exercise heat stress when behavioral thermoregulation cues are ignored.

Post‐exercise hot water immersion induces heat acclimation and improves endurance exercise performance in the heat

We examined whether daily hot water immersion (HWI) after exercise in temperate conditions induces heat acclimation and improves endurance performance in temperate and hot conditions. Seventeen non‐heat‐acclimatized males performed a 6‐day intervention involving a daily treadmill run for 40 min at 65% V̇O2max in temperate conditions (18 °C) followed immediately by either HWI (N = 10; 40 °C) or thermoneutral (CON, N = 7; 34 °C) immersion for 40 min. Before and after the 6‐day intervention, participants performed a treadmill run for 40 min at 65% V̇O2max followed by a 5‐km treadmill time trial (TT) in temperate (18 °C, 40% humidity) and hot (33 °C, 40% humidity) conditions. HWI induced heat acclimation demonstrated by lower resting rectal temperature (Tre, mean, −0.27 °C, P < 0.01), and final Tre during submaximal exercise in 18 °C (−0.28 °C, P < 0.01) and 33 °C (−0.36 °C, P < 0.01). Skin temperature, Tre at sweating onset and RPE were lower during submaximal exercise in 18 °C and 33 °C after 6 days in HWI (P < 0.05). Physiological strain and thermal sensation were also lower during submaximal exercise in 33 °C after 6 days in HWI (P < 0.05). HWI improved TT performance in 33 °C (4.9%, P < 0.01) but not in 18 °C. Thermoregulatory measures and performance did not change in CON. Hot water immersion after exercise on 6 days presents a simple, practical, and effective heat acclimation strategy to improve endurance performance in the heat.

Effects of a daily mixed nutritional supplement on physical performance, body composition, and circulating anabolic hormones during 8 weeks of arduous military training.

The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d⁻¹ during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program.

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 skins 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.

Influence of modest changes in whole-body hydration on tear fluid osmolarity: important considerations for dry eye disease detection.

To the Editors: We read with great interest a recent article published in Cornea, and recent articles published elsewhere, describing the measurement of tear fluid osmolarity (Tosm) as a suitable biomarker for dry eye disease (DED). Indeed, the authors of the article published in Cornea indicate that Tosm measurement using the TearLab system could become the ‘‘gold standard’’ in DED detection. We believe that it is important to bring to the attention of your readers the findings of our very recent study using the TearLab system, and 2 important issues regarding DED detection using Tosm. We have shown (in young, healthy, non-DEDmales and females with basal Tosm 293 SD 9 mOsmol L ) that Tosm increases and correlates extremely well (r = 0.93) with a widely accepted marker of hydration, plasma osmolality, during modest dehydration evoked by exercise and overnight fluid restriction. By including a control trial in which participants exercised in the same conditions (33(C and 50% relative humidity) with fluid intake to offset fluid losses, we showed a decrease in Tosm that tracked the decrease in plasma osmolality indicating that our dehydration results were not an exercise artifact. The results of the controlled trial also discounted an effect of the environmental conditions (eg, evaporation) on Tosm. Our results indicate to those working in the field of hydration assessment that the TearLab device has potential utility as a noninvasive hydration assessment tool. We would like to draw to the attention of those working in the vision and ophthalmology field 2 important issues regarding DED detection using Tosm. First, although we evoked only modest dehydration (2%–3% body mass loss), Tosm was equal to or greater than the recently proposed DED threshold of 316 mOsm L 1 in 5 of our 14 participants. Clearly, these results indicate that an individual’s presenting hydration status should be considered when using Tosm to indicate DED (ie, dehydration could lead to an incorrect DED diagnosis). Second, and perhaps more importantly, given that increased Tosm is thought to be involved in ocular inflammation and compensatory events in DED, we speculate that chronic dehydration may play a role in the etiology of DED. We recognize that the etiology of DED seems to be multifactorial, but it is worth noting that DED is more prevalent in the elderly than in the young, and so too is chronic dehydration. As such, a potential confounding effect of acute changes in hydration on DED detection using Tosm and a potential involvement of chronic dehydration in the etiology of DED warrant further inquiry. Financial disclosures/conflicts of interest: None reported.

O3.20: Non-invasive clinical and physical signs, symptoms and indications for identification of impending and current water-loss dehydration in older people: a diagnostic accuracy systematic review

Introduction Water-loss dehydration is common in older people and associated with excess morbidity and mortality, but it is unclear which signs/symptoms identify dehydration in this group. Diagnostic accuracy of possible clinical and physical signs, symptoms and indications of water-loss dehydration in older people were assessed against serum osmolality or weight change (reference standards)1. Methods Structured searches were run in seven databases. Assessment of inclusion, data extraction and assessment of validity were duplicated. Where data sets included index tests and a reference standard, but were not analysed for diagnostic accuracy, reviewers analysed the data. Diagnostic accuracy of each sign, symptom or indicator was assessed against the best reference standard, and data presented in sensitivity and specificity forest plots. Pre-set minimum sensitivity was 60%, specificity 75%. Secondary analyses created receiver operating characteristic (ROC) curves for continuous tests. Results We included 24 studies (3 using published data, 21 analysing raw data sets) reporting 67 tests. No index tests were reproducibly usefully diagnostic of water-loss dehydration in older people, but promising signs/symptoms, which need further assessment, are shown in the table. There was sufficient evidence to suggest that some signs/symptoms should not be used to indicate dehydration (table). Conclusions No single sign/symptom was diagnostic of water-loss dehydration in older people. Individual signs should not be used in this population to indicate dehydration as they will miss many with dehydration, and wrongly label those adequately hydrated. Promising signs identified by this review need to be further assessed. 1. Hooper L et al, Cochrane Library (protocol) 2011: CD009647-DOI:1002/14651858.