Cardiopulmonary exercise testing in younger patients with persistent dyspnea following acute, outpatient COVID-19 infection.

Studies using cardiopulmonary exercise testing (CPET) to evaluate persistent dyspnea following infection with COVID-19 have focused on older patients with co-morbid diseases who are post-hospitalization. Less attention has been given to younger patients with post-COVID-19 dyspnea treated as outpatients for their acute infection. We sought to determine causes of persistent dyspnea in younger patients recovering from acute COVID-19 infection that did not require hospitalization. We collected data on all post-COVID-19 patients who underwent CPET in our clinic in the calendar year 2021. Data on cardiac function and respiratory response were abstracted, and diagnoses were assigned using established criteria. CPET data on 45 patients (238.3 ± 124 days post-test positivity) with a median age of 27.0 (22.0-40.0) were available for analysis. All but two (95.6%) were active-duty service members. The group showed substantial loss of aerobic capacity-average VO2 peak (L/min) was 84.2 ± 23% predicted and 25 (55.2%) were below the threshold for normal. Spirometry, diffusion capacity, high-resolution computed tomography, and echocardiogram were largely normal and were not correlated with VO2 peak. The two most common contributors to dyspnea and exercise limitation following comprehensive evaluation were deconditioning and dysfunctional breathing (DB). Younger active-duty military patients with persistent dyspnea following outpatient COVID-19 infection show a substantial reduction in aerobic capacity that is not driven by structural cardiopulmonary disease. Deconditioning and DB breathing are common contributors to their exercise limitation. The chronicity and severity of symptoms accompanied by DB could be consistent with an underlying myopathy in some patients, a disorder that cannot be differentiated from deconditioning using non-invasive CPET.

Correlation of Impulse Oscillometry with Spirometry in Deployed Military Personnel with Airway Obstruction.

INTRODUCTION: Evaluation of chronic respiratory symptoms in deployed military personnel has been conducted at Brooke Army Medical Center as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Although asthma and airway hyperreactivity have been the most common diagnoses, the clinical findings in these patients may be multifactorial. This study aims to evaluate the utility of impulse oscillometry (IOS) in diagnosing airway obstruction in patients undergoing multiple pulmonary function testing (PFT) studies. METHODS: Military personnel referred for deployed-related pulmonary symptoms underwent a standardized evaluation at Brooke Army Medical Center and Walter Reed National Military Medical Center over a 5-year span. Initial studies included laboratory tests, high-resolution computed tomography imaging, cardiac evaluation with electrocardiogram, and echocardiography. PFT consisted of full PFTs, forced inspiratory/expiratory pressures, post-spirometry bronchodilator testing, IOS, exhaled nitric oxide, and methacholine challenge testing. RESULTS: A total of 360 patients have completed an evaluation to date. In this cohort, 108 patients (30.0%) have evidence of obstruction by spirometry, whereas 74 (20.6%) had IOS values of both an R5 > 150% and X5 < -1.5. Only 32 (8.9%) had evidence of obstruction by both spirometry and IOS, whereas 210 (57.3%) had neither. A comparison among R5 (resistance at 5 Hz), R20 (resistance at 20 Hz), and X5 (reactance at 5 Hz) was performed in those individuals with and without spirometric obstruction. R5 (% predicted) was 156.2 ± 57.4% (obstruction) vs. 129.1 ± 39.6% (no obstruction) (P < .001); R20 (% predicted) was 138.1 ± 37.7% (obstruction) vs. 125.3 ± 31.2% (no obstruction) (P = .007); and X5 (cmH2O/L/s) was -1.62 ± 1.28 (obstruction) vs. -1.25 ± 0.55 (no obstruction) (P < .001). DISCUSSION: Impulse oscillometry has been advocated as a supplemental pulmonary function test to aid in the diagnosis of airway obstruction. The use of IOS has been primarily used in pediatrics and elderly populations as a validated tool to establish a diagnosis of airway obstruction but is limited in the adult population because of a well-validated set of reference values. Prior studies in adults have most often demonstrated a correlation with an elevated R5 > 150%, elevated resonant frequency, and a negative X5 < -1.5 or a decrease of 30 to 35% in R5 post-bronchodilator. CONCLUSION: Impulse oscillometry may serve as an adjunct to diagnosis but likely cannot replace a standard spirometric evaluation. Our study highlights the future utility for diagnosing early obstructive disease in the symptomatic individual.

Obesity-related Changes in Diffusing Capacity and Transfer Coefficient of the Lung for Carbon Monoxide and Resulting Patterns of Abnormality across Reference Equations.

Rationale: In 2017, an American Thoracic Society/European Respiratory Society Task Force report recommended further research on the effects that body mass index (BMI) has on diffusing capacity of the lung for carbon monoxide (DlCO), the transfer coefficient (Kco), and the alveolar volume (VA). Objectives: Our goals were to 1) quantify the magnitude and direction of change to measured and predicted DlCO values as BMI increases in patients free of cardiopulmonary disease and 2) identify how BMI and obesity-related changes differ by reference set. Methods: Using data from a prospective cohort study of service members free of cardiopulmonary disease, we modeled the effect that BMI has on measured values of DlCO, Kco, and VA, after adjusting for age, sex, hemoglobin (Hgb), and height. We then referenced DlCO, Kco, and VA to normal values using four different reference equations. Results: There were 380 patients with data available for analysis, and 130 had a BMI ⩾ 30 kg/m2 (87.7% class I obesity). After controlling for age, sex, Hgb, and height, increased BMI was significantly associated with Kco (ß = 0.09, P < 0.01) and VA (ß = -0.15, P < 0.01) but not DlCO. After adjustment for Hgb, for every 5-kg/m2 increase in BMI, the mean increase in percent predicted (PPD) values ranged from 4.2% to 6.5% and from 5.0% to 7.5% for DlCO and Kco, respectively; and the mean decrease in VA PPD was 3.2-4.0%. In the presence of obesity (BMI ⩾ 30 kg/m2), the prevalence of DlCO and Kco abnormalities dropped by 4.1-12.1% and 0.4-16.3%, respectively, across equations, whereas VA abnormalities increased from 7.7% to 9.9%. Eliminating 163 patients with abnormal trans-thoracic echocardiogram (TEE), high-resolution computed tomographic (HRCT) scan, or Hgb altered the magnitude of relationships, but significance was preserved. Conclusions: In an otherwise healthy population with predominantly class I obesity and normal TTE, HRCT scan, and Hgb, we found that Kco and VA were more affected by BMI than DlCO. Increases in PPD values varied across equations and were modest but significant and could change clinical decision making by reducing sensitivity for detecting gas-exchange abnormalities. BMI and obesity had the smallest effect on Global Lung Function Initiative PPD values.

Thromboprophylaxis in Patients With COVID-19: A Brief Update to the CHEST Guideline and Expert Panel Report.

BACKGROUND: Patients hospitalized with COVID-19 often exhibit markers of a hypercoagulable state and have an increased incidence of VTE. In response, CHEST issued rapid clinical guidance regarding prevention of VTE. Over the past 18 months the quality of the evidence has improved. We thus sought to incorporate this evidence and update our recommendations as necessary. STUDY DESIGN AND METHODS: This update focuses on the optimal approach to thromboprophylaxis in hospitalized patients. The original questions were used to guide the search, using MEDLINE via PubMed. Eight randomized controlled trials and one observational study were included. Meta-analysis, using a random effects model, was performed. The panel created summaries using the GRADE Evidence-to-Decision framework. Updated guidance statements were drafted, and a modified Delphi approach was used to obtain consensus. RESULTS: We provide separate guidance statements for VTE prevention for hospitalized patients with acute (moderate) illness and critically ill patients in the ICU. However, we divided each original question and resulting recommendation into two questions: standard prophylaxis vs therapeutic (or escalated dose) prophylaxis and standard prophylaxis vs intermediate dose prophylaxis. This led to a change in one recommendation, and an upgrading of three additional recommendations based upon higher quality evidence. CONCLUSIONS: Advances in care for patients with COVID-19 have improved overall outcomes. Despite this, rates of VTE in these patients remain elevated. Critically ill patients should receive standard thromboprophylaxis for VTE, and moderately ill patients with a low bleeding risk might benefit from therapeutic heparin. We see no role for intermediate dose thromboprophylaxis in either setting.

Obstructive sleep apnea among survivors of combat-related traumatic injury: a retrospective cohort study.

STUDY OBJECTIVES: Obstructive sleep apnea is prevalent among military members despite fewer traditional risk factors. We sought to determine the incidence and longitudinal predictors of obstructive sleep apnea in a large population of survivors of combat-related traumatic injury and a matched control group. METHODS: Retrospective cohort study of military service members deployed to conflict zones from 2002-2016 with longitudinal follow-up in the Veterans Affairs and Military Health Systems. Two cohorts of service members were developed: (1) those who sustained combat injuries and (2) matched, uninjured participants. RESULTS: 17,570 service members were retrospectively analyzed for a median of 8.4 years. After adjustment, traumatic brain injury (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.20-1.60), posttraumatic stress disorder (HR 1.24, 95% CI 1.05-1.46), depression (HR 1.52, 95% CI 1.30-1.79), anxiety (HR 1.40, 95% CI 1.21-1.62), insomnia (HR 1.71, 95% CI 1.44-2.02), and obesity (HR 2.40, 95% CI 2.09-2.74) were associated with development of obstructive sleep apnea. While combat injury was associated with obstructive sleep apnea in the univariate analysis (HR 1.25, 95% CI 1.17-1.33), the direction of this association was reversed in the multivariable model (HR 0.74, 95% CI 0.65-0.84). In a nested analysis, this was determined to be due to the effect of mental health diagnoses. CONCLUSIONS: The incidence of obstructive sleep apnea is higher among injured service members (29.1 per 1,000 person-years) compared to uninjured service members (23.9 per 1,000 person-years). This association appears to be driven by traumatic brain injury and the long-term mental health sequelae of injury. CITATION: Haynes ZA, Stewart IJ, Poltavskiy EA, et al. Obstructive sleep apnea among survivors of combat-related traumatic injury: a retrospective cohort study. J Clin Sleep Med. 2022;18(1):171-179.

Postpulmonary embolism syndrome.

PURPOSE OF REVIEW: It is now recognized that more than half of patients with acute pulmonary embolism (APE) will have persistent symptoms beyond 3 months after their initial event. Persistent symptoms are referred to as post-PE syndrome, an umbrella term that covers a spectrum of patient complaints and underlying pathologies. Data published over the last 5 years have added significantly to our understanding of this syndrome and its management. RECENT FINDINGS: Underlying pathologies linked to post-PE syndrome include chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic disease (CTED), cardiac dysfunction, and deconditioning. Treatment for post-PE syndrome will depend on the underlying causative pathologies found. Evaluation and treatment for CTEPH is well defined, but less than 10% of patients with post-PE syndrome will qualify as having this diagnosis. SUMMARY: A large percentage of patients will experience post-PE syndrome following APE. Strategies for identification and treatment for some pathologies are well studied, but the majority of patients will have subtle abnormalities on imaging and functional testing for which diagnostic criteria and management are not well defined. A number of active studies are designed to help optimize the management of post-PE syndrome and should help us improve intermediate and long-term outcomes for patients following APE.

Risk factors of persistent insomnia among survivors of traumatic injury: a retrospective cohort study.

STUDY OBJECTIVES: Insomnia is a diagnosis with broad health and economic implications that has been increasingly recognized in military service members. This trend was concurrent with an increase in traumatic wartime injuries. Accordingly, we sought to determine longitudinal predictors of persistent insomnia in combat veterans who sustained traumatic injuries. METHODS: Retrospective cohort study of service members deployed to conflict zones from 2002 to 2016, with longitudinal follow-up in the Veterans Affairs and Military Health Systems. Two cohorts were derived: (1) service members who sustained traumatic injuries and (2) an age-, sex-, and service component-matched cohort of uninjured service members who deployed to a combat zone. Insomnia was defined using International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision-Clinical Modification codes. RESULTS: The final population of 17,374 service members was followed from date of injury (or date of matched participant's injury) for a median of 8.4 (interquartile range, 5.3-10.7) years. Service members with traumatic injury were at significantly greater risk of developing insomnia than uninjured service members (hazard ratio = 1.43; 95% confidence interval, 1.30-1.58) after adjustment. Traumatic brain injury was associated with insomnia compared with patients without traumatic brain injury in the multivariable model: mild/unclassified traumatic brain injury (hazard ratio = 2.07; 95% confidence interval, 1.82-2.35) and moderate/severe/ penetrating traumatic brain injury (hazard ratio = 2.43; 95% confidence interval, 2.06-2.86). Additionally, burn injury (hazard ratio = 1.95; 95% confidence interval, 1.47-2.59) and amputation (hazard ratio = 1.61; 95% confidence interval, 1.26-2.06) significantly increased the risk of a diagnosis. CONCLUSIONS: Traumatic injuries significantly predicted a diagnosis of insomnia after controlling for mental health disorders. Our findings strongly suggest the need for long-term surveillance of sleep disorders in trauma survivors. CITATION: Haynes ZA, Collen JF, Poltavskiy EA, et al. Risk factors of persistent insomnia among survivors of traumatic injury: a retrospective cohort study. J Clin Sleep Med. 2021;17(9):1831-1840.

Posttraumatic Stress Disorder Is Associated With a Decrease in Anaerobic Threshold, Oxygen Pulse, and Maximal Oxygen Uptake.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been linked to respiratory symptoms and functional limitations, but the mechanisms leading to this association are poorly defined. RESEARCH QUESTION: What is the relationship between PTSD, lung function, and the cardiopulmonary response to exercise in combat veterans presenting with chronic respiratory symptoms? STUDY DESIGN AND METHODS: This study prospectively enrolled military service members with respiratory symptoms following deployment to southwest Asia. All participants underwent a comprehensive evaluation that included pulmonary function testing and cardiopulmonary exercise testing. Pulmonary function test variables and cardiopulmonary response to exercise were compared in subjects with and without PTSD by using multivariable linear regression to adjust for confounders. RESULTS: A total of 303 participants were included (PTSD, n = 70; non-PTSD, n = 233). Those with PTSD had a greater frequency of current respiratory symptoms. There were no differences in measures for airway disease or lung volumes, but patients with PTSD had a reduction in diffusing capacity that was eliminated following adjustment for differences in hemoglobin levels. Participants with PTSD had a lower anaerobic threshold (23.9 vs 26.4 cc/kg per minute; P = .004), peak oxygen pulse (19.7 vs 18.5 cc/beat; P = .03), and peak oxygen uptake (34.5 vs 38.8 cc/kg per minute; P < .001). No significant difference was observed in gas exchange, respiratory reserve, or effort at peak exercise between participants with and without PTSD. INTERPRETATION: A diagnosis of PTSD was associated with a reduced anaerobic threshold, oxygen pulse, and peak oxygen uptake. This objective reduction in cardiopulmonary work is independent of baseline lung function, was not associated with abnormalities in gas exchange or respiratory reserve, and may be related to deconditioning.

Optimizing routine screening for cardiac sarcoidosis through use of commonly available studies.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder with unclear etiology. Morbidity and mortality vary based on organ involvement, with cardiac sarcoidosis (CS) associated with higher mortality; despite this, CS remains underdiagnosed. The Heart Rhythm Society (HRS) expert consensus statement recommends screening sarcoidosis patients for CS utilizing a symptom screen, EKG, and echocardiogram (TTE), while the American Thoracic Society (ATS) guideline recommends only EKG and symptom screening. These recommendations, however, are based on limited data with recommendations for further studies. RESEARCH QUESTION: The purpose is to evaluate the prevalence of abnormal screening tests in patients with sarcoidosis and the correlation of these tests with the subsequent diagnosis of CS. A specific emphasis was placed on evaluating the sensitivity of the recommendations versus the sensitivity of a modified criteria. STUDY DESIGN: and Methods: This study retrospectively evaluated a database of prospectively enrolled patients from a tertiary military academic center. All patients who underwent imaging with cardiac MRI and/or FDG-PET were identified. These results were correlated with screening studies (symptom screen, EKG, TTE, and ambulatory rhythm monitoring (ARM)) and used to calculate sensitivity, specificity, and positive and negative predictive values for each test. Using a clinical diagnosis of CS as the reference standard, the sensitivity and specificity of the HRS criteria were calculated and compared to a modified screening rubric developed a priori, consisting of minor changes to the criteria and the addition of ARM. RESULTS: This study evaluated 114 patients with sarcoidosis with 132 advanced imaging events, leading to a diagnosis of CS in 36 patients. Utilizing HRS screening recommendations, the sensitivity for CS was 63.9%, while the modified criteria increased sensitivity to 94.4%. INTERPRETATION: This study suggests that the HRS guidelines lack sensitivity to effectively screen for CS and that a modified screening model which includes ARM may be more effective.

Prevention, diagnosis, and treatment of VTE in patients with Coronavirus Disease 2019: CHEST guideline and expert panel report

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE. This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report.

BACKGROUND: Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE. This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. METHODS: A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. RESULTS: The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. CONCLUSIONS: The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Isolated Small Airway Dysfunction and Ventilatory Response to Cardiopulmonary Exercise Testing.

BACKGROUND: The effect of isolated small airway dysfunction (SAD) on exercise remains incompletely characterized. We sought to quantify the relationship between isolated SAD, identified with lung testing, and the respiratory response to exercise. METHODS: We conducted a prospective evaluation of service members with new-onset dyspnea. All subjects underwent plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), impulse oscillometry, high-resolution computed tomography (HRCT), and cardiopulmonary exercise testing (CPET). In subjects with normal basic spirometry, DLCO, and HRCT, SAD measures were analyzed for associations with ventilatory parameters at submaximal exercise and at maximal exercise during CPET. RESULTS: We enrolled 121 subjects with normal basic spirometry (ie, FEV1, FVC, and FEV1/FVC), DLCO, and HRCT. Mean age and body mass index were 37.4 ± 8.8 y and 28.4 ± 3.8 kg/m2, respectively, and 110 (90.9%) subjects were male. The prevalence of SAD varied from 2.5% to 28.8% depending on whether FEV3/FVC, FEF25-75%, residual volume/total lung capacity, and R5-R20 were used to identify SAD. Agreement on abnormal SAD across tests was poor (kappa = -0.03 to 0.07). R5-R20 abnormalities were related to higher minute ventilation ([Formula: see text]) and higher [Formula: see text]/maximum voluntary ventilation (MVV) during submaximal exercise and to lower [Formula: see text] during maximal exercise. After adjustment for differences at baseline, there remained a trend toward a relationship between R5-R20 and an elevated [Formula: see text]/MVV during submaximal exercise (ß = 0.04, 95% CI -0.01 to 0.09, P = .10), but there was no significant association with [Formula: see text] during submaximal exercise or with [Formula: see text] during maximal exercise. No other SAD measures showed a relationship with ventilatory parameters. CONCLUSIONS: In 121 subjects with normal basic spirometry, DLCO, and HRCT, we found poor agreement across tests used to detect SAD. Among young, healthy service members with postdeployment dyspnea, SAD as identified by lung function testing does not predict changes in the ventilatory response to exercise.

Clinical Evaluation of Deployed Military Personnel With Chronic Respiratory Symptoms: Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE) III.

BACKGROUND: Chronic respiratory symptoms are frequently reported after Southwest Asia deployment in support of combat operations. The full spectrum of clinical lung diseases related to these deployments is not well characterized. METHODS: Military personnel with chronic symptoms, primarily exertional dyspnea, underwent a standardized cardiopulmonary evaluation at two tertiary medical centers. Pulmonary function testing consisted of spirometry, lung volume, diffusing capacity, impulse oscillometry, and bronchodilator testing. Further testing included methacholine challenge, exercise laryngoscopy, high-resolution CT scan, ECG, and transthoracic echocardiography. RESULTS: A total of 380 participants with a mean age of 38.5 ± 8.4 years completed testing. Asthma was the most common diagnosis in 87 patients (22.9%) based on obstructive spirometry/impulse oscillometry and evidence of airway hyperreactivity, whereas another 57 patients (15.0%) had reactivity with normal spirometry. Airway disorders included 25 (6.6%) with laryngeal disorders and 16 (4.2%) with excessive dynamic airway collapse. Interstitial lung disease was identified in six patients (1.6%), whereas 11 patients (2.9%) had fixed obstructive lung disorders. Forty patients (10.5%) had isolated pulmonary function abnormalities and 16 (4.2%) had miscellaneous disorders. The remaining 122 patients (32.1%) with normal studies were classified as undiagnosed exertional dyspnea. Significant comorbidities identified included elevated BMI > 30 kg/m2 (34.2%), smoking (36.4%), positive allergy testing (43.7%), sleep apnea (38.5%), and esophageal reflux (13.6%). Mental health disorders and posttraumatic stress disorder were likewise common. CONCLUSIONS: Postdeployment pulmonary evaluation should focus on common diseases, such as asthma and airway hyperreactivity, and include testing for upper airway disorders. Diffuse lung diseases were rarely diagnosed, whereas numerous comorbidities were common.