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.

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.

Effects of Exercise Training on Pulmonary Function in Adults With Chronic Lung Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To quantify the effect of exercise training on indices of pulmonary function in adults with chronic lung disease using meta-analytic techniques. DATA SOURCES: Eligible trials were identified using a systematic search of MEDLINE, Web of Science, Physiotherapy Evidence Database, and GoogleScholar databases. STUDY SELECTION: Randomized controlled trials that evaluated pulmonary function before and after whole-body exercise training among adult patients (aged ≥19y) with chronic lung disease were included. DATA EXTRACTION: Data were independently extracted from each study by 3 authors. Random-effects models were used to aggregate a mean effect size (Hedges' d; Δ) and 95% confidence interval (CI), and multilevel linear regression with robust maximum likelihood estimation was used to adjust for potential nesting effects. DATA SYNTHESIS: Among 2923 citations, a total of 105 weighted effects from 21 randomized controlled trials were included. After adjusting for nesting effects, exercise training resulted in a small (Δ=.18; 95% CI, .07-.30) and significant (P=.002) improvement in a composite measure of pulmonary function. Tests of heterogeneity of the mean effect size were nonsignificant. CONCLUSIONS: Contrary to prior assumptions, whole-body exercise training is effective for improving pulmonary function in adults with chronic lung disease, particularly spirometric indices. Subsequent studies are necessary to determine the optimal exercise training characteristics to maximize functional improvement.

Salivary Mitochondrial DNA Copy Number Is Associated With Exercise Ventilatory Efficiency.

Chen, Y, Hill, HZ, Lange, G, and Falvo, MJ. Salivary mitochondrial DNA copy number is associated with exercise ventilatory efficiency. J Strength Cond Res 31(7): 2000-2004, 2017-Mitochondrial DNA copy number (mtDNAcn) is an index of mitochondrial content and is responsive to changes in exercise training volume. Therefore, assessment of mtDNAcn may help to optimize exercise prescription and aid in athlete monitoring. Although previous work has assessed mtDNAcn derived from skeletal muscle and blood using invasive approaches, no study has examined salivary mtDNAcn and its relationship with sport performance. Fifteen adults (32.2 ± 7.1 years) volunteered to participate in this study. Each participant provided a saliva sample for the analysis of mtDNAcn via real-time polymerase reaction. In addition, participants completed an exercise challenge test to assess oxygen consumption relative to body weight (V[Combining Dot Above]O2·kg) and ventilatory efficiency (VE/V[Combining Dot Above]CO2). Using multiple linear regression, we examined the association of V[Combining Dot Above]O2·kg and VE/V[Combining Dot Above]CO2 with salivary mtDNAcn, adjusting for self-reported physical activity (min·wk). Greater mtDNAcn was associated with lower VE/V[Combining Dot Above]CO2 (p < 0.01) and higher V[Combining Dot Above]O2·kg (p < 0.05). In our model adjusted for physical activity, greater mtDNAcn remained associated with lower VE/V[Combining Dot Above]CO2 (ß = -0.186; 95% confidence interval [CI], -0.348 to -0.025; p < 0.05), but not with V[Combining Dot Above]O2·kg (ß = -0.022; 95% CI, -0.113 to 0.063). Our findings suggest that salivary mtDNAcn is associated with ventilatory efficiency, which may reflect enhanced exercise efficiency as a consequence of greater total mitochondrial content. As saliva collection is noninvasive, stable at room temperature, and less costly in comparison to skeletal muscle and blood, future studies may consider using saliva for the evaluation of mitochondrial content for the purposes of monitoring exercise training as well as optimizing exercise prescription.

Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans.

More than 2.6 million military personnel have been deployed to recent conflicts in Iraq and Afghanistan and were likely exposed to a variety of airborne hazards during deployment. Despite several epidemiologic reports of increased respiratory symptoms, whether or not these respiratory illnesses lead to reductions in lung function and/or specific pulmonary disease is unclear. We reviewed data published from 2001 to 2014 pertaining to respiratory health in military personnel deployed to Iraq and Afghanistan and found 19 unique studies. Study designs were primarily retrospective and observational in nature with patient symptom reporting and medical encounter data as primary outcome measures. Two case series reported on rare respiratory diseases, and one performed a standardized evaluation of new-onset respiratory symptoms. Respiratory outcomes in relation to proximity to a specific air pollution source (i.e., smoke from burning trash and sulfur mine fire) were described in 2 separate studies. Only 2 longitudinal investigations were identified comparing pre- and postdeployment measurement of exercise capacity. In summary, published data based on case reports and retrospective cohort studies suggest a higher prevalence of respiratory symptoms and respiratory illness consistent with airway obstruction. However, the association between chronic lung disease and airborne hazards exposure requires further longitudinal research studies with objective pulmonary assessments.

Ambient and household air pollution: complex triggers of disease.

Concentrations of outdoor air pollution are on the rise, particularly due to rapid urbanization worldwide. Alternatively, poor ventilation, cigarette smoke, and other toxic chemicals contribute to rising concentrations of indoor air pollution. The World Health Organization recently reported that deaths attributable to indoor and outdoor air pollutant exposure are more than double what was originally documented. Epidemiological, clinical, and animal data have demonstrated a clear connection between rising concentrations of air pollution (both indoor and outdoor) and a host of adverse health effects. During the past five years, animal, clinical, and epidemiological studies have explored the adverse health effects associated with exposure to both indoor and outdoor air pollutants throughout the various stages of life. This review provides a summary of the detrimental effects of air pollution through examination of current animal, clinical, and epidemiological studies and exposure during three different periods: maternal (in utero), early life, and adulthood. Additionally, we recommend future lines of research while suggesting conceivable strategies to curb exposure to indoor and outdoor air pollutants.

Kansas squat test: a reliable indicator of short-term anaerobic power.

The purposes of this study were to establish stability reliability of a measure of lower-body anaerobic power, the Kansas squat test (KST), and to compare the KST with the commonly used Wingate anaerobic test (WAnT) for lower-body power. Fourteen resistance-trained men (mean ± SD; age = 24.2 ± 3.6 years) performed both the KST and the WAnT twice on separate occasions. The KST consisted of using an external dynamometer to measure mean repetition power while performing 15 repetitions of speed squats using 70% of 1 repetition maximum system mass (barbell + body mass), initiating each repetition at 6-second intervals. Repetition power, mean power for all 15 repetitions, and % fatigue for the KST were all reliable (intraclass correlation coefficient = 0.754-0.937; p ≤ 0.05). There were no differences between tests for the mean power for all repetitions or relative fatigue (p ≤ 0.05) and no significant differences between tests for any individual repetition (test × repetition interaction, p < 0.05). Although absolute values were different (p > 0.05), significant correlations were found between the KST and WAnT for mean (r = 0.752) and maximum (r = 0.775) test powers but not for relative fatigue (r = 0.174). Lactate (HLa) responses were greater for the WAnT compared with the KST. These data indicate that the KST is reliable for resistance-trained men, and that measures of maximum and mean test powers for the KST are highly correlated to those values for the WAnT, but fatigue rates and HLa responses were not correlated. It appears that the KST is a lifting-specific anaerobic power and power endurance test that emphasizes phosphagen metabolism and may be used to assess training-induced changes in lower-body power.

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.].

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.

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.

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.

A retrospective cohort study of U.S. service members returning from Afghanistan and Iraq: is physical health worsening over time?

BACKGROUND: High rates of mental health disorders have been reported in veterans returning from deployment to Afghanistan (Operation Enduring Freedom: OEF) and Iraq (Operation Iraqi Freedom: OIF); however, less is known about physical health functioning and its temporal course post-deployment. Therefore, our goal is to study physical health functioning in OEF/OIF veterans after deployment. METHODS: We analyzed self-reported physical health functioning as physical component summary (PCS) scores on the Veterans version of the Short Form 36 health survey in 679 OEF/OIF veterans clinically evaluated at a post-deployment health clinic. Veterans were stratified into four groups based on time post-deployment: (1Yr) 0 - 365 days; (2Yr) 366 - 730 days; (3Yr) 731 - 1095 days; and (4Yr+) > 1095 days. To assess the possibility that our effect was specific to a treatment-seeking sample, we also analyzed PCS scores from a separate military community sample of 768 OEF/OIF veterans evaluated pre-deployment and up to one-year post-deployment. RESULTS: In veterans evaluated at our clinic, we observed significantly lower PCS scores as time post-deployment increased (p = 0.018) after adjusting for probable post-traumatic stress disorder (PTSD). We similarly observed in our community sample that PCS scores were lower both immediately after and one year after return from deployment (p < 0.001) relative to pre-deployment PCS. Further, PCS scores obtained 1-year post-deployment were significantly lower than scores obtained immediately post-deployment (p = 0.02). CONCLUSION: In our clinical sample, the longer the duration between return from deployment and their visit to our clinic, the worse the Veteran's physical health even after adjusting for PTSD. Additionally, a decline is also present in a military community sample of OEF/OIF veterans. These data suggest that, as time since deployment length increases, physical health may deteriorate for some veterans.

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.

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.