Effect of Ultra-Marathon Trail Running at Sea Level and Altitude on Alveolar-Capillary Function and Lung Diffusion.

INTRODUCTION: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress-tolerability of the alveolar-capillary unit. This study examined the effect of ultra-marathon trail racing at different altitudes (ranging from <1000 m to between 1500 - 2700 m) on alveolar-capillary recruitment and lung diffusion. METHODS: Cardiac and lung function were examined before and after an ultra-marathon in 67 runners (age:41 ± 9y, BMI:23 ± 2 kg/m2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI & BNP) were assessed from whole blood, while lung fluid accumulation (comet tails), stroke volume (SV) and cardiac output (Q) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semi-recumbent cycling (20, 30, & 40 W). RESULTS: Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± .02 vs 0.13 ± .03 ng/ml; BNP: 20 ± 2 vs 112 ± 21 pg/ml, p < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, p < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 ml; 40 W: 93 ± 2 vs 88 ± 2 ml, p < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 l/min, p < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 l/min, p = 0.899). Resting DLco and Vc decreased after the race (p < 0.01), while Dm was unchanged (p = 0.465); however, during the three stages of exercise DLco, Vc and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL/min/mmHg; 83 ± 3 vs 73 ± 2 mL; 186 ± 6 vs 170 ± 7 mL/min/mmHg, respectively, p < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race (p < 0.01), and changes in DLco were similar for all ultra-marathon events (p > 0.05). CONCLUSIONS: Competing in an ultra-marathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultra-marathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

Metabolic insights at the finish line: deciphering physiological changes in ultramarathon runners through breath VOC analysis.

Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Sex-Specific Physiological Responses to Ultramarathon.

PURPOSE: Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males. METHODS: Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase-MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min). RESULTS: Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL -1 ; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L -1 ; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL -1 ; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L -1 ; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL -1 ; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DL CO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min -1 ⋅mm Hg -1 , P = 0.004; DL NO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min -1 ⋅mm Hg -1 , P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females ( d = 0.86 vs 0.63). CONCLUSIONS: Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.

Alveolar to arterial gas exchange during constant-load exercise in healthy active men and women.

Inadequate hyperventilation and inefficient alveolar to arterial gas exchange are gas exchange challenges that can limit capacity and cause exercise-induced arterial hypoxaemia (EIAH). This work evaluated if the prevalence of gas exchange inefficiencies, defined as AaDO2>25 mmHg, PaCO2>38 mmHg, and/or ΔPaO2>-10 mmHg at any point during constant-load exercise in healthy, active, but not highly trained, individuals suggested an innate sex difference that would make females more susceptible to EIAH. Sixty-four healthy, active males and females completed 18-min of cycling exercise (moderate and vigorous intensity, 9 min/stage). Arterial blood gases were measured at rest and every 3-min during exercise, while constantly assessing gas exchange. Both sexes demonstrated similar levels of AaDO2 widening until the final 3 min of vigorous exercise, where females demonstrated a trend for greater widening than males (16.3±6.2 mmHg vs. 19.1±6.0 mmHg, p=0.07). Males demonstrated a blunted ventilatory response to moderate exercise with higher PaCO2 (38.5±2.6 vs. 36.5±2.4, p=0.002) and a lower ventilation when corrected for workload (0.42±0.1 vs. 0.48±0.1, p=0.002). No significant arterial hypoxaemia occurred, but in 6 M and 5 F SaO2 dropped by ≥2%. There was no difference in prevalence of pulmonary gas exchange inefficiencies between sexes, but the type of inefficiency was influenced by sex.Abbreviations: AaDO2: alveolar-arterial oxygen difference; BP: blood pressure; EIAH: exercise-induced arterial hypoxaemia; F: females; HR: heart rate; M: males; Q: cardiac output; PaCO2: arterial partial pressure of carbon dioxide; PaO2: arterial partial pressure of oxygen; ΔPaO2: change in arterial partial pressure of oxygen; PAO2: alveolar partial pressure of oxygen; RPE: rating of perceived exertion; SaO2: arterial oxygen saturation; VE: ventilation; VE/VCO2: ventilatory equivalent for carbon dioxide; VO2PEAK: peak oxygen consumption; WMAX: workload maximum.

Hypersensitivity reactions to high osmolality Total Parenteral Nutrition: a case report.

BACKGROUND: The full range of allergic reactions to Total Parenteral Nutrition (TPN) remains unknown. Additionally, beyond individual allergens, there may be other factors contributing to TPN hypersensitivity reactions. CASE PRESENTATION: We present a case of a patient with negative skin testing to common TPN allergens who had recurrent urticarial reactions to TPN. Her skin reactions resolved once TPN was stopped. Following a literature review, we postulated that the reactions could be due to the high osmolality of her TPN. Consequently, lowering her TPN from 2785 to 1928 mOsm/kg and premedicating with cetirizine resulted in resolution of her urticaria. CONCLUSIONS: When looking at patients who have hypersensitivity reactions to TPN, one must consider that their reactions may be due to factors other than allergens. More studies are needed to clarify the relationship between high osmolality TPN infusions and non-IgE mediated hypersensitivity reactions.

Outcomes from an inpatient beta-lactam allergy guideline across a large US health system.

OBJECTIVE: To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported ß-lactam allergies. DESIGN: Retrospective cohort study. SETTING: Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017. METHODS: We evaluated ß-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified. RESULTS: We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%-9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%-5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34-6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%). CONCLUSION: This antimicrobial stewardship intervention using ß-lactam test-dose procedures was safe. Overall, 3.8% of patients with ß-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.

A 'crying wolf' game of interspecific kleptoparasitic mutualism.

We model a potentially mutualistic interaction between a species making antipredator alarm calls and a species which eavesdrops on those calls. Callers may or may not make deceptive alarm calls in order to kleptoparasitize food from eavesdroppers, which in turn may either heed or ignore all alarm calls. The two most likely outcomes in our model are either maximally deceptive callers and maximally trusting eavesdroppers, or persistently cycling strategy frequencies. The latter is favoured by low predator density, low density of any alternative honest alarm-calling species, ability of eavesdroppers to preferentially heed calls when costs of doing so are low and, in some cases, low food availability.

Substernal epicardial echocardiography: review of a new technique.

BACKGROUND: Patients after cardiac operation pose a challenge to the treating physician-these patients may become critically ill and are among the most difficult to image using transthoracic echocardiography. Several factors contribute to this, including difficulties in positioning the patient, inability of the patient to cooperate with instructions, surgical dressings, and hyperinflated lungs. Transesophageal echocardiography may be performed when transthoracic echocardiography is not diagnostic; however, transesophageal echocardiography is semi-invasive and does not lend itself to prolonged or repeated monitoring. METHODS: Recently, a new approach to echocardiography for use in the patient after operation has been introduced with the modification of the standard mediastinal drainage tube to allow for substernal epicardial echocardiography (SEE). The SEE tube has 2 lumens. The first allows for routine mediastinal drainage and the second has a blind end that permits the insertion of a standard transesophageal echocardiographic probe for high-resolution imaging as often as is desired over the period during which the mediastinal tube is in place. CONCLUSION: This article reviews the technique of SEE including a description of the method of performance of SEE (with representative images), a review of the published literature on this new modality, examples of clinical use, and a discussion of the advantages, indications, and limitations of SEE with an eye toward future directions for research.