Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose-response, crossover study.

Chronic multisymptom illnesses (CMI) such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Long-COVID, and Gulf War Illness (GWI) are associated with an elevated risk of post-exertional malaise (PEM), an acute exacerbation of symptoms and other related outcomes following exercise. These individuals may benefit from personalized exercise prescriptions which prioritize risk minimization, necessitating a better understanding of dose-response effects of exercise intensity on PEM. METHODS: Veterans with GWI (n = 40) completed a randomized controlled crossover experiment comparing 20 min of seated rest to light-, moderate-, and vigorous-intensity cycling conditions over four separate study visits. Symptoms, pain sensitivity, cognitive performance, inflammatory markers (C-reactive protein and plasma cytokines) were measured before and within 1 h after exercise and seated rest. Physical activity behavior was measured ≥ 7 days following each study visit via actigraphy. Linear mixed effects regression models tested the central hypothesis that higher intensity exercise would elicit greater exacerbation of negative outcomes, as indicated by a significant condition-by-time interaction for symptom, pain sensitivity, cognitive performance, and inflammatory marker models and a significant main effect of condition for physical activity models. RESULTS: Significant condition-by-time interactions were not observed for primary or secondary measures of symptoms, pain sensitivity, cognitive performance, and a majority of inflammatory markers. Similarly, a significant effect of condition was not observed for primary or secondary measures of physical activity. CONCLUSIONS: Undesirable effects such as symptom exacerbation were observed for some participants, but the group-level risk of PEM following light-, moderate-, or vigorous-intensity exercise was no greater than seated rest. These findings challenge several prior views about PEM and lend support to a broader body of literature showing that the benefits of exercise outweigh the risks.

Correction: Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness.

[This corrects the article DOI: 10.1371/journal.pone.0287412.].

Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness.

Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.

Deployed Veterans exhibit distinct respiratory patterns and greater dyspnea during maximal cardiopulmonary exercise: A case-control study.

BACKGROUND: Exertional dyspnea and exercise intolerance are frequently endorsed in Veterans of post 9/11 conflicts in Southwest Asia (SWA). Studying the dynamic behavior of ventilation during exercise may provide mechanistic insight into these symptoms. Using maximal cardiopulmonary exercise testing (CPET) to experimentally induce exertional symptoms, we aimed to identify potential physiological differences between deployed Veterans and non-deployed controls. MATERIALS AND METHODS: Deployed (n = 31) and non-deployed (n = 17) participants performed a maximal effort CPET via the Bruce treadmill protocol. Indirect calorimetry and perceptual rating scales were used to measure rate of oxygen consumption ([Formula: see text]), rate of carbon dioxide production ([Formula: see text]), respiratory frequency (f R), tidal volume (VT), minute ventilation ([Formula: see text]), heart rate (HR), perceived exertion (RPE; 6-20 scale), and dyspnea (Borg Breathlessness Scale; 0-10 scale). A repeated measures analysis of variance (RM-ANOVA) model (2 groups: deployed vs non-deployed X 6 timepoints: 0%, 20%, 40%, 60%, 80%, and 100% [Formula: see text]) was conducted for participants meeting valid effort criteria (deployed = 25; non-deployed = 11). RESULTS: Significant group (η2partial = 0.26) and interaction (η2partial = 0.10) effects were observed such that deployed Veterans exhibited reduced f R and a greater change over time relative to non-deployed controls. There was also a significant group effect for dyspnea ratings (η2partial = 0.18) showing higher values in deployed participants. Exploratory correlational analyses revealed significant associations between dyspnea ratings and fR at 80% (R2 = 0.34) and 100% (R2 = 0.17) of [Formula: see text], but only in deployed Veterans. CONCLUSION: Relative to non-deployed controls, Veterans deployed to SWA exhibited reduced fR and greater dyspnea during maximal exercise. Further, associations between these parameters occurred only in deployed Veterans. These findings support an association between SWA deployment and affected respiratory health, and also highlight the utility of CPET in the clinical evaluation of deployment-related dyspnea in Veterans.

Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.

Background: Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. Objectives: To investigate whether PEM is meditated by gene expression in Veterans with GWI. Methods: Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Results: Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p < 0.05). Expression of ß -actin (ACTB), catechol-O-methyltransferase (COMT), and toll-like receptor 4 (TLR4) decreased in Veterans with GWI at 30 min (p < 0.05) and 24 h post-exercise (p < 0.05). Changes in gene expression did not mediate post-exercise symptom exacerbation in GWI (Indirect Effect Slope Coefficient: 0.06 - 0.02; 95% CI: 0.19, 0.12). Conclusion: An acute bout of moderate intensity cycling reduced the expression of select structural, adrenergic, and immune genes in Veterans with GWI, but the pathophysiological relevance to PEM is unclear.

Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What are the recommended diagnostic workup and associated terminology of respiratory symptoms in previously deployed individuals? STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: Twenty-five of 28 statements reached consensus, including the definition of CB as a histologic pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms, distinguishing assessments best performed at a local or specialty referral center. Also, deployment-related respiratory disease (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through noninvasive evaluation or when surgical lung biopsy reveals evidence of multicompartmental lung injury that may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of postdeployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and to define other features of its natural history, which could inform physicians better and lead to evolution in this nosology.

Factors associated with a diagnosis of sarcoidosis among US veterans of Iraq and Afghanistan.

This study evaluated risk factors of sarcoidosis among Airborne Hazards and Open Burn Pit Registry (AHOBPR) participants using a retrospective age and sex-matched case-control design of AHOBPR participants deployed to Afghanistan or Southwest Asia with and without sarcoidosis diagnosed in the Veterans Health Administration (VHA). Logistic regression models tested for associations between sarcoidosis and self-reported cumulative deployment-related exposures. 661 Veterans (0.37%) were diagnosed with sarcoidosis in VHA. Logistic regression demonstrated lower odds of sarcoidosis in Hispanic participants (OR 0.08, CI 0.04-0.15) and those who served in the Navy (OR 0.40, CI 0.21-0.72). African American veterans (OR 2.27, CI 1.66-3.11) and former smokers (OR 1.87, CI 1.33-2.62) were at elevated risk. Of the exposure variables, convoy activities had the highest odds of being associated with sarcoidosis and was marginally statistically significant (OR 1.16, CI 1.00-1.35). Sarcoidosis was an uncommon diagnosis among AHOBPR participants and was associated with only one of eight assessed cumulative deployment-related exposures.

Postdeployment Respiratory Health: The Roles of the Airborne Hazards and Open Burn Pit Registry and the Post-Deployment Cardiopulmonary Evaluation Network.

Background: Following deployment to the Southwest Asia theater of operations and Afghanistan, many service members and veterans report respiratory symptoms and concerns about their military and environmental exposures. The US Department of Veterans Affairs (VA) established the national Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 to help better understand long-term health conditions that may be related to these exposures. Observations: The AHOBPR provides an online questionnaire and optional health evaluation performed by a primary care or environmental health clinician. The clinical evaluation provides an opportunity for the service member or veteran to talk with a health care professional about their symptoms, exposures, and potential treatment. Data derived from questionnaire responses and health evaluations facilitate medical surveillance and research. The VA also established a network of specialists, referred to as the Post-Deployment Cardiopulmonary Evaluation Network (PDCEN). The PDCEN identifies veterans within the AHOBPR who self-report certain conditions or have unexplained dyspnea and conducts comprehensive diagnostic evaluations. Primary objectives of PDCEN evaluations are to define respiratory and related conditions that are present, determine whether conditions are related to deployment, and work with the veteran's clinician to identify treatments and/or follow-up care to improve their health. We utilize a case example to illustrate the role of the primary care practitioner in connecting veterans to PDCEN clinical evaluations. Conclusions: AHOBPR clinical evaluations represent an initial step to better understand postdeployment health conditions. The PDCEN clinical evaluation extends the AHOBPR evaluation by providing specialty care for certain veterans requiring more comprehensive evaluation while systematically collecting and analyzing clinical data to advance the field.

Short-term PM exposure and social stress cause pulmonary and cardiac dysfunction.

Ambient particulate matter (PM) exposure increases risk for cardiopulmonary health problems which may be exacerbated in a stressful environment. Co-exposure to PM and stress characterizes the experience of many deployed military personnel and first responders but has not been thoroughly investigated. This is especially relevant to military personnel who have been exposed to high PM levels in conjunction with stressful military conflict situations. To understand the mechanisms and time-course of the health consequences following burn pit exposure, we exposed mice to moderate levels of ambient PM less than 2.5 µM in diameter (PM2.5) alone or in combination with psychological stress. We found male mice exposed to PM2.5 alone or in combination with stress had significantly reduced pulmonary function when subjected to methacholine, indicating increased airway hyperreactivity. These mice experienced increased goblet cell hyperplasia in their lungs, with no change in alveolar density. Mice exposed to PM2.5 and/or stress also exhibited reduced cardiac contractility, right ventricular (RV) output, and changes in RV capillary density and cardiac inflammatory markers. Taken together, these data indicate that short-term exposure to PM2.5 with or without stress causes a clear reduction in pulmonary and cardiac function. We believe that this model is well-suited for the study of military and other occupational exposures, and future work will identify potential mechanisms, including the inflammatory progression of these co-exposures.

An analysis of alternative forced oscillation technique reporting and validation methods for within- and between-sessions in healthy adults.

Forced oscillation technique (FOT) provides unique information on respiratory system mechanical properties complementing pulmonary function testing. However, a lack of evidence guiding acquisition/reporting of parameters has slowed clinical FOT adoption. Current European Respiratory Society (ERS) standards recommend 3-5 trials per session comprising three trials with a coefficient of variation (CoV) ≤ 10% for low-frequency resistance. We present an analysis of different combinations of trial selection methods and session validity thresholding variables (low- and mid-frequency resistance and reactance [R5, R19, X5], low-frequency reactance area [AX] and tidal volume) comparing proportion of subjects achieving valid data across two test sessions (7 ± 3 days apart) and within and between session measurement variabilities. 126 (98%) subjects achieved valid data across both sessions (2666 trials). With R5 or R19 as criteria and selection of any three trials from ≥ 4 attempts, ≥ 75% of subjects achieved validity. Furthermore, with R5 or R19 criteria and selection of any trials from ≥ 5 attempts, CoVs for resistance outcomes were reduced within session while variabilities of FOT outcomes between sessions remained consistent. Within session differences in measurement variabilities were not clinically meaningful. Our analyses support current ERS reporting recommendations for healthy adults. Future work should apply this analytic approach to patient populations.

Pain, but not Physical Activity, is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic Pain.

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.

Relationship between clinician documented blast exposure and pulmonary function: a retrospective chart review from a national specialty clinic.

BACKGROUND: Service member exposure to explosive blast overpressure waves is common with considerable attention to traumatic brain injury (TBI) and neuropsychological sequalae. Less is known about the impacts on the respiratory system, particularly long-term effects, despite vulnerability to overpressure. Using a national registry, we previously observed an independent relationship between self-reported blast exposure and respiratory symptoms; however, the impact on objective measures of pulmonary function is poorly understood. METHODS: 307 Veterans referred to our national specialty center for post-deployment health concerns underwent a comprehensive multi-day evaluation that included complete pulmonary function testing (PFT), occupational and environmental medicine history, neuropsychological or psychological evaluation. We developed an a priori chart abstraction process and template to classify Veterans into blast exposure groups: (1) none, (2) single-mild, or (3) multiple-mild. This template focused primarily on clinician documented notes of blast related TBI that were used as proxy for blast overpressure injury to thorax. PFT variables characterizing flow (FEV1%; %∆FEV1), volume (TLC%), diffusion (DLCO%) and respiratory mechanics (forced oscillometry) were selected for analysis. RESULTS: Veterans (40.5 ± 9.7 years; 16.3% female) were referred 8.6 ± 3.6 years after their last deployment and presented with considerable comorbid conditions and health problems (e.g., 62% post-traumatic stress, 55% dyspnea). After chart abstraction, Veterans were assigned to none (n = 208), single mild (n = 52) and multiple mild (n = 47) blast exposure groups. Among the blast exposed, clinicians documented 73.7% were < 50 m from the blast and 40.4% were physically moved by blast. PFT outcome measures were similar across all groups (p value range: 0.10-0.99). CONCLUSIONS: In this referred sample of deployed Veterans, PFT measures of flow, volume, diffusion, and respiratory mechanics were not associated with clinician documented blast exposure per the retrospective chart abstraction methodology applied. Yet, these clinical findings suggest future research should determine and assess distinction between Veteran recollections of perceived blast experiences versus overpressure wave exposure to the respiratory system.

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study.

BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Employing the Forced Oscillation Technique for the Assessment of Respiratory Mechanics in Adults.

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and diseased individuals. FOT, a complementary method to traditional pulmonary function testing, utilizes a range of oscillatory frequencies superimposed on tidal breathing to measure the functional relationship between airway pressure and flow. This passive assessment provides an estimate of respiratory system resistance (Rrs) and reactance (Xrs) that reflect airway caliber and energy storage and dissipation, respectively. Despite the recent increase in popularity and updated Technical Standards, clinical adoption has been slow which relates, in part, to the lack of standardization regarding the acquisition and reporting of FOT data. The goal of this article is to address the lack of standardization across laboratories by providing a comprehensive written protocol for FOT and an accompanying video. To illustrate that this protocol can be utilized irrespective of a particular device, three separate FOT devices have been employed in the case examples and video demonstration. This effort is intended to standardize the use and interpretation of FOT, provide practical suggestions, as well as highlight future questions that need to be addressed.

A comparison of alternative selection methods for reporting spirometric parameters in healthy adults.

Alternative methods have been proposed to report spirometry indices from test sessions (forced expiratory volume 1 s, FEV1; forced vital capacity, FVC). However, most use the American and European Societies' standard (ATS/ERS) which stops sessions once a repeatability threshold is met which may not accurately represent intra-session variability. Our goal was to repeat trials beyond the repeatability threshold and evaluate alternative reporting methods. 130 adults performed spirometry across two visits. Spirometry indices were reported using the ATS/ERS standard and four alternatives. 78 participants (60%) had valid data for all methods and visits. Intra-session coefficients of variation were low (FEV1: 3.1-3.7%; FVC: 2.3-2.8%). Our four alternative methods yielded FEV1 and FVC values ≤ 0.08 L different from ATS/ERS standard, which is not clinically meaningful. Intraclass correlation coefficients were ≥ 0.97 indicating consistency across repeated measures. The smallest real differences ranged from FEV1: 0.20-0.27 L and FVC: 0.18-0.24 L indicating consistency and low measurement error. Overall, all methods for reporting FEV1 and FVC demonstrated similar measurement error, precision, and stability within- and between-visits. These results suggest that once ATS/ERS repeatability is achieved, which approach is used for reporting spirometric variables may be of low clinical significance in a healthy population.

Predicting post-exertional malaise in Gulf War Illness based on acute exercise responses.

AIMS: Post-exertional malaise (PEM) is poorly understood in Gulf War Illness (GWI). Exercise challenges have emerged as stimuli to study PEM; however, little attention has been paid to unique cardiorespiratory and perceptual responses during exercise. This study tested whether select exercise parameters explained variability in PEM responses. MAIN METHODS: Visual analog scale (0-100) versions of the Kansas questionnaire were used for daily symptom measurements one week before and one week after 30-min of cycling at 70% heart rate reserve in 43 Veterans with GWI and 31 Veteran controls (CON). Cardiopulmonary exercise testing (CPET) methods were used to measure oxygen (VO2), carbon dioxide (VCO2), ventilation (VE), heart rate, work rate, and leg muscle pain. Symptom changes and CPET parameters were compared between groups with independent samples t-tests. Linear regression (GLM) with VE/VCO2, cumulative work, leg muscle pain, and self-reported physical function treated as independent variables and peak symptom response as the dependent variable tested whether exercise responses predicted PEM. KEY FINDINGS: Compared to CON, Veterans with GWI had greater ventilatory equivalent for oxygen (VE/VO2), peak leg muscle pain, fatigue, and lower VCO2, VO2, power, and cumulative work during exercise (p < 0.05), and greater peak symptom responses (GWI = 38.90 ± 29.06, CON = 17.84 ± 28.26, g = 0.70, p < 0.01). The final GLM did not explain significant variance in PEM (Pooled R2 = 0.15, Adjusted R2 = 0.03, p = 0.34). SIGNIFICANCE: The PEM response was not related to the selected combination of cardiorespiratory and perceptual responses to exercise.

Hemorheological responses to an acute bout of maximal exercise in Veterans with Gulf War Illness.

BACKGROUND: Altered red blood cell (RBC) deformability has been reported in Veterans with Gulf War Illness (GWI) who endorse exercise-induced symptom exacerbation and fatigue. However, it is unknown whether altered RBC deformability is worsened secondary to exercise. OBJECTIVE: To evaluate RBC deformability in response to maximal exercise in individuals with and without GWI. METHODS: Seventeen Veterans with GWI and 11 controls performed maximal exercise and provided blood samples (pre-, immediately post- and 60-min post-exercise). We calculated RBC deformation at infinite stress (EIMAX), shear stress for half-deformation (SS1/2) and their ratio (SS1/2/EIMAX) via repeated measures ANOVA with group and time as factors. RESULTS: A moderate interaction effect (p = 0.08, η2p = 0.10), large main effect for group (p = 0.02, η2p = 0.19) and moderate main effect for time (p = 0.20, η2p = 0.06) were observed for EIMAX, but only the main effect for group reached statistical significance. Changes in SS1/2 and SS1/2/EIMAX over time were similar between cases and controls as were main effects. CONCLUSIONS: Veterans with GWI had more deformable RBCs in comparison to controls that was unaffected by maximal exercise. Future studies to confirm our findings and identify associated mechanisms are warranted.