Effects of 5-Week Oral Acetazolamide on Incremental Cycling Exercise in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Randomized Placebo-Controlled, Double-Blinded, Crossover Trial.

INTRODUCTION: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. METHODS: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. RESULTS: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference -4 W (95% CI: -9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5-1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3-19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. CONCLUSION: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.

Cognitive and Emotional Responses to Chronic Obstructive Pulmonary Disease Exacerbations and Patterns of Care Seeking.

Rationale: Cognitive and emotional responses associated with care seeking for chronic obstructive pulmonary disease (COPD) exacerbations are not well understood.Objectives: We sought to define care-seeking profiles based on whether and when U.S. veterans seek care for COPD exacerbations and compare cognitive and emotional responses with exacerbation symptoms across the profiles.Methods: This study analyzes data from a 1-year prospective observational cohort study of individuals with COPD. Cognitive and emotional responses to worsening symptoms were measured with the Response to Symptoms Questionnaire, adapted for COPD. Seeking care was defined as contacting or visiting a healthcare provider or going to the emergency department. Participants were categorized into four care-seeking profiles based on the greatest delay in care seeking for exacerbations when care was sought: 0-3 days (early), 4-7 days (short delay), >7 days (long delay), or never sought care for any exacerbation. The proportion of exacerbations for which participants reported cognitive and emotional responses was estimated for each care-seeking profile, stratified by the timing of when care was sought.Results: There were 1,052 exacerbations among 350 participants with Response to Symptoms Questionnaire responses. Participants were predominantly male (96%), and the mean age was 69.3 ± 7.2 years. For the 409 (39%) exacerbations for which care was sought, the median delay was 3 days. Those who sought care had significantly more severe COPD (forced expiratory volume in 1 s, modified Medical Research Council dyspnea scale) than those who never sought care. Regardless of the degree of delay until seeking care at one exacerbation, participants consistently reported experiencing serious symptoms if they sought care compared with events for which participants did not seek care (e.g., among early care seekers when care was sought, 36%; when care was not sought, 25%). Similar findings were seen in participants' assessment of the importance of getting care (e.g., among early care seekers when care was sought, 90%; when care was not sought, 52%) and their assessment of anxiety about the symptoms (e.g., among early care seekers when care was sought, 33%; when care was not sought, 17%).Conclusions: Delaying or not seeking care for COPD exacerbations was common. Regardless of care-seeking profile, cognitive and emotional responses to symptoms when care was sought differed from responses when care was not sought. Emotional and cognitive response to COPD exacerbations should be considered when developing individualized strategies to encourage seeking care for exacerbations.Clinical trial registered with www.clinicaltrials.gov (NCT02725294).

Predictors of Patient-reported and Pharmacy Refill Measures of Maintenance Inhaler Adherence in Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Suboptimal adherence to inhaled medications in patients with chronic obstructive pulmonary disease (COPD) remains a challenge. Objectives: To examine the sociodemographic and clinical characteristics and medication beliefs associated with adherence measured by self-report and pharmacy data. Methods: A cross-sectional analysis of data from a prospective observational cohort study of patients with COPD was completed. Participants underwent spirometry and completed questionnaires regarding sociodemographic data, inhaler use, dyspnea, social support, psychological and medical comorbidities, and medication beliefs (Beliefs about Medicines Questionnaire [BMQ]). Self-reported adherence to inhaled medications was measured with the Adherence to Refills and Medications Scale (ARMS), and pharmacy-based adherence was calculated from administrative data using the ReComp score. Multivariable linear regression was used to examine the sociodemographic, clinical, and medication-belief factors associated with both adherence measures. Results: Among 269 participants with ARMS and ReComp data, adherence was the same for each measure (38.3%), but only 18% of participants were adherent by both measures. In multivariable adjusted analysis, a 10-year increase in age (ß = 0.54; 95% confidence interval, 0.14-0.94) and the number of maintenance inhalers used (ß = 0.53; 0.04-1.02) were associated with increased adherence by self-report. Improved ReComp adherence was associated with chronic prednisone use (ß = 0.18; 0.04-0.31) and the number of maintenance inhalers used (ß = 0.11; 0.05-0.17). In adjusted analyses examining patient beliefs about medications, increases in the COPD-specific BMQ concerns score (ß = -0.10; -0.17 to -0.02) were associated with reduced self-reported adherence. No significant associations between ReComp adherence and BMQ score were found in adjusted analyses. Conclusions: Adherence to inhaled COPD medications was poor as measured by self-report or pharmacy refill data. There were notable differences in factors associated with adherence based on the method of adherence measurement. Older age, chronic prednisone use, the number of prescribed maintenance inhalers used, and patient beliefs about medication safety were associated with adherence. Overall, fewer variables were associated with adherence as measured based on pharmacy refills. Pharmacy refill-based and self-reported adherence may measure distinct aspects of adherence and may be affected by different factors. These results also underscore the importance of addressing patient beliefs when developing interventions to improve medication adherence.

Asymmetric and symmetric dimethylarginine in high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE).

Introduction: High altitude exposure may lead to high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE). The pathophysiologic processes of both entities have been linked to decreased nitric oxide (NO) availability. Methods: We studied the effect of acute high altitude exposure on the plasma concentrations of asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-arginine, L-ornithine, and L-citrulline in two independent studies. We further investigated whether these biomarkers involved in NO metabolism were related to HAPH and HAPE, respectively. Fifty (study A) and thirteen (study B) non-acclimatized lowlanders were exposed to 4,559 m for 44 and 67 h, respectively. In contrast to study A, the participants in study B were characterized by a history of at least one episode of HAPE. Arterial blood gases and biomarker concentrations in venous plasma were assessed at low altitude (baseline) and repeatedly at high altitude. HAPE was diagnosed by chest radiography, and HAPH by measuring right ventricular to atrial pressure gradient (RVPG) with transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and the AMS-C score. Results: In both studies SDMA concentration significantly increased at high altitude. ADMA baseline concentrations were higher in individuals with HAPE susceptibility (study B) compared to those without (study A). However, upon high altitude exposure ADMA only increased in individuals without HAPE susceptibility, while there was no further increase in those with HAPE susceptibility. We observed an acute and transient decrease of L-ornithine and a more delayed but prolonged reduction of L-citrulline during high altitude exposure. In both studies SDMA positively correlated and L-ornithine negatively correlated with RVPG. ADMA was significantly associated with the occurrence of HAPE (study B). ADMA and SDMA were inversely correlated with alveolar PO2, while L-ornithine was inversely correlated with blood oxygenation and haemoglobin levels, respectively. Discussion: In non-acclimatized individuals ADMA and SDMA, two biomarkers decreasing endothelial NO production, increased after acute exposure to 4,559 m. The observed biomarker changes suggest that both NO synthesis and arginase pathways are involved in the pathophysiology of HAPH and HAPE.

Association between self-reported falling risk and risk of hospitalization for patients with chronic obstructive pulmonary disease.

RATIONALE: The association between self-report falling risk in persons with COPD and hospitalization has not been previously explored. OBJECTIVE: To examine whether self-reported risk is associated with hospitalizations in patients with COPD. METHODS: A secondary analysis from a prospective observational cohort study of veterans with COPD. Participants completed questions from the Stopping Elderly Accidents, Deaths and Injuries (STEADI) tool kit at either baseline or at the end of the 12-month study. A prospective or cross-sectional analysis examined the association between responses to the STEADI questions and risk of all-cause or COPD hospitalizations. RESULTS: Participants (N = 388) had a mean age of 69.6 ± 7.5 years, predominately male (96 %), and 144 (37.1 %) reported having fallen in the last year. More than half reported feeling unsteady with walking (52.6 %) or needing to use their arms to stand up from a chair (61.1 %). A third were concerned about falling (33.3 %). Three questions were associated with all-cause (not COPD) hospitalization in both unadjusted and adjusted cross-sectional analysis (N = 213): "fallen in the past year" (IRR 1.77, 95 % CI 1.10 to 2.86); "unsteady when walking" (IRR 1.88, 95 % CI 1.14 to 3.10); "advised to use a cane or walker" (IRR 1.89, 95 % CI 1.16 to 3.08). CONCLUSIONS: The prevalence of self-reported falling risk was high in this sample of veterans with COPD. The association between falling risk and all-cause hospitalization suggests that non-COPD hospitalizations can negatively impact intrinsic risk factors for falling. Further research is needed to clarify the effects of all-cause hospitalization on falling risk in persons with COPD.

Exercise in hypoxia: a model from laboratory to on-field studies.

Clinical outcome and quality of life of patients with chronic heart failure (HF) have greatly improved over the last two decades. These results and the availability of modern lifts allow many cardiac patients to spend leisure time at altitude. Heart failure per se does not impede a safe stay at altitude, but exercise at both simulated and real altitudes is associated with a reduction in performance, which is inversely proportional to HF severity. For example, in normal subjects, the reduction in functional capacity is ∼2% every 1000 m altitude increase, whereas it is 4 and 10% in HF patients with normal or slightly diminished exercise capacity and in HF patients with markedly diminished exercise capacity, respectively. Also, the on-field experience with HF patients at altitude confirms safety and shows overall similar data to that reported at simulated altitude. Even 'optimal' HF treatment in patients spending time at altitude or at hypoxic conditions is likely different from optimal treatment at sea level, particularly with regard to the selectivity of ß-blockers. Furthermore, high altitude, both simulated and on-field, represents a stimulating model of hypoxia in HF patients and healthy subjects. Our data suggest that spending time at altitude (<3500 m) can be safe even for HF patients, provided that subjects are free from comorbidities that may directly interfere with the adaptation to altitude and are stable. However, HF patients experience a reduction of exercise capacity directly proportional to HF severity and altitude. Finally, HF patients should be tested for functional capacity and must undergo a specific 'hypoxic-tailored treatment' to avoid pharmacological interference with altitude adaptation mechanisms, particularly with regard to the selectivity of ß-blockers.

A remote monitoring-enabled home exercise prescription for patients with interstitial lung disease at risk for exercise-induced desaturation.

RATIONALE: Alternatives to center-based pulmonary rehabilitation are needed to improve patient access to this important therapy. A critical challenge to overcome is how to maximize safety of unsupervised exercise for at-risk patients. We investigated if a novel remote monitoring-enabled mobile health (mHealth) program is safe, feasible, and effective for patients who experience exercise-induced hemoglobin desaturation. METHODS: An interstitial lung disease (ILD) commonly associated with pronounced exercise desaturation was investigated - the rare, female-predominant ILD lymphangioleiomyomatosis (LAM). Over a 12-week program, hemoglobin saturation (SpO2) was continuously recorded during all home exercise sessions. Intervention effects were assessed with 6-min walk test (6MWT), maximal cardiopulmonary exercise test (CPET), lower extremity computerized dynamometry, pulmonary function tests, and health-related quality of life (QoL) surveys. Safety was assessed by blood biomarkers of systemic inflammation and cardiac wall stress, and incidence of adverse events. RESULTS: Fifteen LAM patients enrolled and 14 completed the intervention, with high adherence to aerobic (87 ± 15%) and strength (87 ± 12%) training components. An innovative characterization of exercise training SpO2 revealed that while mild-to-moderate desaturation was common during home workouts, participants were able to self-adjust exercise intensity and supplemental oxygen levels to maintain recommended exercise parameters. Significant improvements included 6MWT distance (+36 ± 34 m, p = 0.003), CPET time (p = 0.04), muscular endurance (p = 0.008), QoL (p = 0.009 to 0.03), and fatigue (p = 0.001 to 0.03). Patient acceptability and satisfaction indicators were high, blood biomarkers remained stable (p > 0.05), and no study-related adverse events occurred. CONCLUSION: A remote monitoring-enabled home exercise program is a safe, feasible, and effective approach even for patients who experience exercise desaturation.

European Respiratory Society/American Thoracic Society technical statement: standardisation of the measurement of lung volumes, 2023 update.

This document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted.

Arterial Blood Gases and Acid-Base Regulation.

Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer system plays a pivotal role in maintaining acid-base homeostasis, and measurements of pH, PCO2, and HCO3 - are routinely used in the estimation of metabolic and respiratory disturbance severity. Hypoventilation and hyperventilation cause primary respiratory acidosis and primary respiratory alkalosis, respectively. Metabolic acidosis and metabolic alkalosis have numerous origins, that include alterations in acid or base intake, body fluid losses, abnormalities of intermediary metabolism, and renal, hepatic, and gastrointestinal dysfunction. The concept of the anion gap is used to categorize metabolic acidoses, and urine chloride excretion helps define metabolic alkaloses. Both the lungs and kidneys employ compensatory mechanisms to minimize changes in pH caused by various physiologic and disease disturbances. Treatment of acid-base disorders should focus primarily on correcting the underlying cause and the hemodynamic and electrolyte derangements that ensue. Specific therapies under certain conditions include renal replacement therapy, mechanical ventilation, respiratory stimulants or depressants, and inhibition of specific enzymes in intermediary metabolism disorders.

Effects of greater erythroid Cl-/HCO3- transporter (band 3) expression on ventilation and gas exchange during exhaustive exercise.

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.

Performance and reliability of two frequently used point-of-care blood gas analyzers at 423 and 4,559 m.

BACKGROUND AND OBJECTIVES: Blood gas analyzers (BGA) aid medical decision-making. Their specified performance criteria are based on sea level conditions. However, millions of people are living at high altitude (HA) where the performance of BGAs is poorly characterized. We investigated the effect of exposure to 4,559 m on the reliability and robustness of two BGAs widely used at HA. METHODS: In this prospective study arterial blood samples from 13 volunteers (2 female) with susceptibility to the development of high-altitude pulmonary edema were collected once near sea level at 423 m (nSL423) and three times at high altitude (HA4,559). Samples were measured in triplicate with the cartridge BGAs Rapidpoint 500 (SIE; Siemens Healthcare) and the ABL90 (RAD; Radiometer) to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC) within a mixed model. RESULTS: At nSL423 and HA4,559, 3% and 17% of all data were not reported with SIE, mainly due to clotting of the sample caused by delays because of the frequent automated calibration routines. No data were missing with RAD. ICCs were not significantly lower (mean (min-max) 0.87 (0.68-0.98) vs. 0.94 (0.84-1.00); p = 0.217) with SIE at nSL423, but significantly lower at HA4,559 (0.87 (0.49-1.00) vs. 0.99 (0.96-1.00); p = 0.025). All CVs, except that for arterial oxygen saturation at HA4,559,were higher with SIE . CONCLUSION: In this study, the reliability of RAD was superior to SIE at nSL423 and HA4,559. In contrast to RAD, the performance of SIE declined at HA4,559. SIE was more prone to not reporting all variables, especially at HA4559.

Race and Ethnicity in Pulmonary Function Test Interpretation: An Official American Thoracic Society Statement.

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.

The Impact of Acetazolamide and Methazolamide on Exercise Performance in Normoxia and Hypoxia.

Doherty, Connor J., Jou-Chung Chang, Benjamin P. Thompson, Erik R. Swenson, Glen E. Foster, and Paolo B. Dominelli. The impact of acetazolamide and methazolamide on exercise performance in normoxia and hypoxia. High Alt Med Biol. 24:7-18, 2023.-Carbonic anhydrase (CA) inhibitors are commonly prescribed for acute mountain sickness (AMS). In this review, we sought to examine how two CA inhibitors, acetazolamide (AZ) and methazolamide (MZ), affect exercise performance in normoxia and hypoxia. First, we briefly describe the role of CA inhibition in facilitating the increase in ventilation and arterial oxygenation in preventing and treating AMS. Next, we detail how AZ affects exercise performance in normoxia and hypoxia and this is followed by a discussion on MZ. We emphasize that the overarching focus of the review is how the two drugs potentially affect exercise performance, rather than their ability to prevent/treat AMS per se, their interrelationship will be discussed. Overall, we suggest that AZ hinders exercise performance in normoxia, but may be beneficial in hypoxia. Based upon head-to-head studies of AZ and MZ in humans on diaphragmatic and locomotor strength in normoxia, MZ may be a better CA inhibitor when exercise performance is crucial at high altitude.

Flying to high-altitude destinations: Is the risk of acute mountain sickness greater?

BACKGROUND: Altitude sojourns increasingly attract individuals of all ages and different health statuses due to the appeal of high-altitude destinations worldwide and easy access to air travel. The risk of acute mountain sickness (AMS) when flying to high-altitude destinations remains underemphasized. Thus, this review aims to evaluate the altitude-dependent AMS incidence depending on the mode of ascending, e.g. by air vs terrestrial travel. METHODS: A literature search was performed to identify the observational studies assessing AMS incidence after acute ascent of primarily healthy adults to real high altitude. In addition, placebo arms of interventional trials evaluating the prophylactic efficacy of various drugs have been separately analysed to confirm or refute the findings from the observational studies. Linear regression analyses were used to evaluate the altitude-dependent AMS incidence. RESULTS: Findings of 12 observational studies, in which the AMS incidence in 11 021 individuals ascending to 19 different altitudes (2200-4559 m) was evaluated, revealed an impressive 4.5-fold steeper increase in the AMS incidence for air travel as compared with slower ascent modes, i.e. hiking or combined car and/or air travel and hiking. The higher AMS incidence following transportation by flight vs slower means was also confirmed in placebo-treated participants in 10 studies of drug prophylaxis against AMS. CONCLUSIONS: Due to the short time span in going from low to high altitude, reduced acclimatization likely is the main reason for a higher AMS risk when travelling to high-altitude destinations by flight. To avoid frustrating travel experiences and health risks, appropriate and timely medical advice on how to prepare for air travel to high altitude is of vital importance. Effective preparation options include the use of modern pre-acclimatization strategies and pharmacological prophylaxis by acetazolamide or dexamethasone, or even considering alternate itineraries with more gradual ascent.

Oxygen Therapy Part 1 - History, Physiology, and Evaluation.

History, Physiology, and Evaluation of Oxygen TherapyOxygen is standard therapy for acute cardiopulmonary diseases, and long-term oxygen therapy is common in the outpatient setting. In part I of a two-part review, Wemple and colleagues discuss the physiology of tissue hypoxia, mechanisms of hypoxemia, and its clinical assessment.

Oxygen Therapy Part 2 - Indications and Toxicity.

Oxygen Therapy Part 2: Indications and ToxicityWemple et al. continue their review of oxygen therapy, discussing the acute and chronic indications for oxygen and the delivery of supplemental oxygen (and its potential adverse effects and toxicity).

An update on environment-induced pulmonary edema - "When the lungs leak under water and in thin air".

Acute pulmonary edema is a serious condition that may occur as a result of increased hydrostatic forces within the lung microvasculature or increased microvascular permeability. Heart failure or other cardiac or renal disease are common causes of cardiogenic pulmonary edema. However, pulmonary edema may even occur in young and healthy individuals when exposed to extreme environments, such as immersion in water or at high altitude. Immersion pulmonary edema (IPE) and high-altitude pulmonary edema (HAPE) share some morphological and clinical characteristics; however, their underlying mechanisms may be different. An emerging understanding of IPE indicates that an increase in pulmonary artery and capillary pressures caused by substantial redistribution of venous blood from the extremities to the chest, in combination with stimuli aggravating the effects of water immersion, such as exercise and cold temperature, play an important role, distinct from hypoxia-induced vasoconstriction in high altitude pulmonary edema. This review aims at a current perspective on both IPE and HAPE, providing a comparative view of clinical presentation and pathophysiology. A particular emphasis will be on recent advances in understanding of the pathophysiology and occurrence of IPE with a future perspective on remaining research needs.

The association between arterial-end-tidal carbon dioxide difference and outcomes after out-of-hospital cardiac arrest.

AIM: We sought to determine if the difference between PaCO2 and ETCO2 is associated with hospital mortality and neurologic outcome following out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study of adult patients who achieved return of spontaneous circulation (ROSC) after OHCA over 3 years. The primary exposure was the PaCO2-ETCO2 difference on hospital arrival. The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurologic status at discharge. We used receiver operating characteristic (ROC) curves to determine discrimination threshold and multivariate logistic regression to examine the association between the PaCO2-ETCO2 difference and outcome. RESULTS: Of 698 OHCA patients transported to the hospitals, 381 had sustained ROSC and qualifying ETCO2 and PaCO2 values. Of these, 160 (42%) survived to hospital discharge. Mean ETCO2 was 39 mmHg among survivors and 43 mmHg among non-survivors. Mean PaCO2-ETCO2 was 6.8 mmHg and 9.0 mmHg (p < 0.05) for survivors and non-survivors. After adjustment for Utstein characteristics, a higher PaCO2-ETCO2 difference on hospital arrival was not associated with hospital mortality (OR 0.99, 95% CI: 0.97-1.0) or neurological outcome. Area under the ROC curve or PaCO2-ETCO2 difference was 0.56 (95% CI 0.51-0.62) compared with 0.58 (95% CI 0.52-0.64) for ETCO2. CONCLUSION: Neither PaCO2-ETCO2 nor ETCO2 were strong predictors of survival or neurologic status at hospital discharge. While they may be useful to guide ventilation and resuscitation, these measures should not be used for prognostication after OHCA.