Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients.

BACKGROUND: The complement system, an upstream recognition system of innate immunity, is activated upon SARS-CoV-2 infection. To gain a deeper understanding of the extent and duration of this activation, we investigated complement activation profiles during the acute phase of COVID-19, its persistence post-recovery and dynamic changes in relation to disease severity. METHODS: Serial blood samples were obtained from two cohorts of hospitalized COVID-19 patients (n = 457). Systemic complement activation products reflecting classical/lectin (C4d), alternative (C3bBbP), common (C3bc) and terminal pathway (TCC and C5a) were measured during hospitalization (admission, days 3-5 and days 7-10), at 3 months and after 1 year. Levels of activation and temporal profiles during hospitalization were related to disease severity defined as respiratory failure (PO2/FiO2 ratio <26.6 kPa) and/or admission to intensive care unit, 60-day total mortality and pulmonary pathology after 3 months. FINDINGS: During hospitalization, TCC, C4d, C3bc, C3bBbP and C5a were significantly elevated compared to healthy controls. Severely ill patients had significantly higher levels of TCC and C4d (p < 0.001), compared to patients with moderate COVID-19. Escalated levels of TCC and C4d during hospitalization were associated with a higher risk of 60-day mortality (p < 0.001), and C4d levels were additionally associated with chest CT changes at 3 months (p < 0.001). At 3 months and 1 year, we observed consistently elevated levels of most complement activation products compared to controls. CONCLUSION: Hospitalized COVID-19 patients display prominent and long-lasting systemic complement activation. Optimal targeting of the system may be achieved through enhanced risk stratification and closer monitoring of in-hospital changes of complement activation products.

Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.

BACKGROUND: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. OBJECTIVES: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. METHODS: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. RESULTS: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. CONCLUSION: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.

Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis.

Infection with coronavirus disease-2019 (COVID-19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID-19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID-19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non-hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID-19 was 3·9% [95% confidence interval (CI): 2·1-7·2] during hospitalisation, 0·9% (95% CI: 0·2-3·1) in the three months after discharge and 0·2% (95% CI: 0·00-1·25) in non-hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.

Caspase-1 induces smooth muscle cell growth in hypoxia-induced pulmonary hypertension.

Lung diseases with hypoxia are complicated by pulmonary hypertension, leading to heart failure and death. No pharmacological treatment exists. Increased proinflammatory cytokines are found in hypoxic patients, suggesting an inflammatory pathogenesis. Caspase-1, the effector of the inflammasome, mediates inflammation through activation of the proinflammatory cytokines interleukin (IL)-18 and IL-1ß. Here, we investigate inflammasome-related mechanisms that can trigger hypoxia-induced pulmonary hypertension. Our aim was to examine whether caspase-1 induces development of hypoxia-related pulmonary hypertension and is a suitable target for therapy. Wild-type (WT) and caspase-1-/- mice were exposed to 10% oxygen for 14 days. Hypoxic caspase-1-/- mice showed lower pressure and reduced muscularization in pulmonary arteries, as well as reduced right ventricular remodeling compared with WT. Smooth muscle cell (SMC) proliferation was reduced in caspase-1-deficient pulmonary arteries and in WT arteries treated with a caspase-1 inhibitor. Impaired inflammation was shown in hypoxic caspase-1-/- mice by abolished pulmonary influx of immune cells and lower levels of IL-18, IL-1ß, and IL-6, which were also reduced in the medium surrounding caspase-1 abrogated pulmonary arteries. By adding IL-18 or IL-1ß to caspase-1-deficient pulmonary arteries, SMC proliferation was retained. Furthermore, inhibition of both IL-6 and phosphorylated STAT3 reduced proliferation of SMC in vitro, indicating IL-18, IL-6, and STAT3 as downstream mediators of caspase-1-induced SMC proliferation in pulmonary arteries. Caspase-1 induces SMC proliferation in pulmonary arteries through the caspase-1/IL-18/IL-6/STAT3 pathway, leading to pulmonary hypertension in mice exposed to hypoxia. We propose that caspase-1 inhibition is a potential target for treatment of pulmonary hypertension.

Specific allergen immunotherapy: effect on IgE, IgG4 and chemokines in patients with allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (SIT) is considered as the most effective treatment for Immunoglobulin E (IgE)-mediated allergies. However, how specific immunotherapy attenuates allergic responses is still not clear, but could potentially involve cytokines as well as IgG4-mediated responses. Based on the role of chemokines in IgE-mediated inflammation, we examined the SIT-induced chemokine response in patients with allergic rhinitis. METHODS: We included 35 patients with allergic rhinitis; 20 patients received SIT and 15 patients were not treated with specific immunotherapy. The patients were followed for 3 years. Blood samples were collected before SIT and 3, 5, 7 and 21 weeks and 1, 2 and 3 years after the start of therapy. Total IgE, specific IgE, IgG4 and chemokine levels were assessed. RESULTS: Our main findings were: (i) SIT was associated with an early increase in total and specific IgE during the first 7 weeks, with a subsequent decline, accompanied by a marked increase in specific IgG4 when IgE started to decline; (ii) these SIT-induced responses were accompanied by and in some degree correlated with increased plasma concentrations of the chemokines, monocyte chemoattractant protein (MCP)-1, and eotaxin; and (iii) within the SIT group, these correlations with chemokines were restricted to IgE and IgG4 against birch tree pollen. CONCLUSION: Our findings further support a role for IgG4-mediated mechanisms in the beneficial effects of SIT in patients with allergic rhinitis (AR) and that increased levels of certain chemokines also could be of importance for the effect of such therapy.

Can ventilator settings reduce the negative effects of endotracheal suctioning? Investigations in a mechanical lung model.

BACKGROUND: The insertion of suction devices through endotracheal tubes (ETTs) increases airway resistance and the subsequent suctioning may reduce airway pressures and facilitate atelectasis. The aim of this study was to investigate how airway pressures and tidal volumes change when different combinations of suction equipment and ETT sizes are used, and to what extent unfavorable effects can be ameliorated by choice of ventilator settings. METHODS: A mechanical ventilator was connected to a lung model by ETTs of 9 mm, 8 mm or 7 mm internal diameter (ID) with a pressure transducer inserted distal to the ETT. The effects of suction procedures with bronchoscope and closed catheter systems were investigated during pressure controlled ventilation (PCV) and volume controlled ventilation (VCV). In each mode, the effects of changes in inspiration:expiration (I:E) ratio, trigger sensitivity and suction pressure were examined. RESULTS: The variables that contributed most to negative model airway pressures and loss of tidal volume during suctioning were (in descending order); 1) Small-size ETTs (7-8 mm ID) combined with large diameter suction devices (14-16 Fr); 2) inverse I:E ratio ventilation (in VCV); 3) negative ventilator trigger sensitivity; and 4) strong suction pressure. The pressure changes observed distal to the ETTs were not identical to those detected by the ventilator. CONCLUSIONS: Negative model airway pressure was induced by suctioning through small-size ETTs. The most extreme pressure and volume changes were ameliorated when conventional ventilator settings were used, such as PCV mode with short inspiration time and a trigger function sensitive to flow changes.

COPD and air travel: does hypoxia-altitude simulation testing predict in-flight respiratory symptoms?

The reduced pressure in an aircraft cabin may cause significant hypoxaemia and respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). The current study evaluated whether there is a relationship between hypoxaemia obtained during hypoxia-altitude simulation testing (HAST), simulating an altitude of 2438 m, and the reporting of respiratory symptoms during air travel. 82 patients with moderate to very severe COPD answered an air travel questionnaire. Arterial oxygen tensions during HAST (PaO2HAST) in subjects with and without in-flight respiratory symptoms were compared. The same questionnaire was answered within 1 year after the HAST. Mean ± sd PaO2HAST was 6.3 ± 0.6 kPa and 62 (76%) of the patients had PaO2HAST <6.6 kPa. 38 (46%) patients had experienced respiratory symptoms during air travel. There was no difference in PaO2HAST in those with and those without in-flight respiratory symptoms (6.3 ± 0.7 kPa versus 6.3 ± 0.6 kPa, respectively; p=0.926). 54 (66%) patients travelled by air after the HAST, and patients equipped with supplemental oxygen (n = 23, 43%) reported less respiratory symptoms when flying with than those without such treatment (four (17%) versus 11 (48%) patients; p=0.039). In conclusion, no difference in PaO2HAST was found between COPD patients with and without respiratory symptoms during air travel.

Air travel and chronic obstructive pulmonary disease: a new algorithm for pre-flight evaluation.

BACKGROUND: The reduced pressure in the aircraft cabin may cause significant hypoxaemia and respiratory distress in patients with chronic obstructive pulmonary disease (COPD). Simple and reliable methods for predicting the need for supplemental oxygen during air travel have been requested. OBJECTIVE: To construct a pre-flight evaluation algorithm for patients with COPD. METHODS: In this prospective, cross-sectional study of 100 patients with COPD referred to hypoxia-altitude simulation test (HAST), sea level pulse oximetry at rest (SpO(2 SL)) and exercise desaturation (SpO(2 6MWT)) were used to evaluate whether the patient is fit to fly without further assessment, needs further evaluation with HAST or should receive in-flight supplemental oxygen without further evaluation. HAST was used as the reference method. RESULTS: An algorithm was constructed using a combination of SpO(2 SL) and SpO(2 6MWT). Categories for SpO(2 SL) were >95%, 92-95% and <92%, the cut-off value for SpO(2 6MWT) was calculated as 84%. Arterial oxygen pressure (PaO(2 HAST)) <6.6 kPa was the criterion for recommending supplemental oxygen. This algorithm had a sensitivity of 100% and a specificity of 80% when tested prospectively on an independent sample of patients with COPD (n=50). Patients with SpO(2 SL) >95% combined with SpO(2 6MWT) ≥84% may travel by air without further assessment. In-flight supplemental oxygen is recommended if SpO(2 SL)=92-95% combined with SpO(2 6MWT) <84% or if SpO(2 SL) <92%. Otherwise, HAST should be performed. CONCLUSIONS: The presented algorithm is simple and appears to be a reliable tool for pre-flight evaluation of patients with COPD.

Extreme altitude induces divergent mass reduction of right and left ventricle in mountain climbers.

Mountain climbing at high altitude implies exposure to low levels of oxygen, low temperature, wind, physical and psychological stress, and nutritional insufficiencies. We examined whether right ventricular (RV) and left ventricular (LV) myocardial masses were reversibly altered by exposure to extreme altitude. Magnetic resonance imaging and echocardiography of the heart, dual x-ray absorptiometry scan of body composition, and blood samples were obtained from ten mountain climbers before departure to Mount Everest or Dhaulagiri (baseline), 13.5 ± 1.5 days after peaking the mountain (post-hypoxia), and six weeks and six months after expeditions exceeding 8000 meters above sea level. RV mass was unaltered after extreme altitude, in contrast to a reduction in LV mass by 11.8 ± 3.4 g post-hypoxia (p = 0.001). The reduction in LV mass correlated with a reduction in skeletal muscle mass. After six weeks, LV myocardial mass was restored to baseline values. Extreme altitude induced a reduction in LV end-diastolic volume (20.8 ± 7.7 ml, p = 0.011) and reduced E', indicating diastolic dysfunction, which were restored after six weeks follow-up. Elevated circulating interleukin-18 after extreme altitude compared to follow-up levels, might have contributed to reduced muscle mass and diastolic dysfunction. In conclusion, the mass of the RV, possibly exposed to elevated afterload, was not changed after extreme altitude, whereas LV mass was reduced. The reduction in LV mass correlated with reduced skeletal muscle mass, indicating a common denominator, and elevated circulating interleukin-18 might be a mechanism for reduced muscle mass after extreme altitude.

Pulse oximetry in the preflight evaluation of patients with chronic obstructive pulmonary disease.

INTRODUCTION: In a British Thoracic Society (BTS) statement on preflight evaluation of patients with respiratory disease, sea level pulse oximetry (Spo2sl) is recommended as an initial assessment. The present study aimed to evaluate if the BTS algorithm can be used to identify chronic obstructive pulmonary disease (COPD) patients in need of supplemental oxygen during air travel, i.e. patients with an in-flight PaO2 < 6.6 kPa (50 mmHg). METHODS: There were 100 COPD patients allocated to groups according to the BTS algorithm: Spo2sl > 95%, Spo2sl 92-95% without additional risk factors; Spo2sl 92-95% with additional risk factors; Spo2sl < 92%; and patients using domiciliary oxygen. Pulse oximetry, arterial blood gases, and an hypoxia-altitude simulation test (HAST) to simulate a cabin altitude of 2438 m (8000 ft), were performed. RESULTS: The percentage of patients in the various groups dropping below 6.6 kPa during HAST were: Spo2sl > 95%: 30%; Spo2sl 92-95% without additional risk factors: 67%; Spo2sl 92-95% with additional risk factors: 70%; Spo2sl < 92%: 83%; and patients using domiciliary oxygen: 81%. In patients dropping below P(a)o(2) 6.6 kPa, supplemental oxygen of median 1 L x min(-1) was needed to exceed this limit. DISCUSSION: If in-flight P(a)o(2) > or = 6.6 kPa is regarded as a strict requirement, the use of pulse oximetry as an initial assessment in the preflight evaluation of COPD patients, as suggested by the BTS, might not discriminate adequately between patients who fulfill the indications for supplemental oxygen during air travel, and patients who can travel without such treatment.

Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells.

Fibrinogen in plasma includes three main fractions; high-molecular-weight (HMW)-fibrinogen, low-molecular-weight (LMW)-fibrinogen, and very-low-molecular-weight (LMW')-fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear. We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6, TNF-alpha and IL-1 beta, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep. HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF-alpha in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF-alpha concentrations were 12 (5, 40) pg/ml and 16 (0,61) pg/ml, respectively. Median mRNA quantity was increased 12.3- (6.6, 48.6) and 1.7- (1.5, 6.5) fold for IL-6 and TNF-alpha compared to controls. The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC. The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.

A daily glass of red wine induces a prolonged reduction in plasma viscosity: a randomized controlled trial.

Moderate red wine consumption has been associated with decreased risk of coronary heart disease. Reduced plasma viscosity and fibrinogen levels have been launched as possible contributors to this risk reduction. The effect of moderate red wine consumption on plasma viscosity, however, has not been investigated in a prospective, randomized trial. We wanted to evaluate the effect of moderate red wine consumption on plasma viscosity, fibrinogen concentration and fibrinogen subfractions. Healthy, nonsmoking volunteers were assigned to consume one glass of red wine daily for 3 weeks in a prospective, randomized cross-over study. In the second 3-week period the volunteers abstained from alcohol use. The plasma viscosity, fibrinogen concentration and the distribution of the main fibrinogen subfractions were determined at inclusion, after wine drinking and after abstention. Plasma viscosity was reduced by 0.026 and 0.024 mPa.s in the two groups following wine intake (95% confidence interval, 0.009-0.043, P = 0.004; 95% confidence interval, 0.0083-0.039, P = 0.003). The decrease in plasma viscosity was maintained following 3 weeks of abstention. The fibrinogen concentration was reduced by 0.17 g/l following wine drinking in the group starting with abstention (95% confidence interval, 0.04-0.29, P = 0.01). The distribution of the fibrinogen subfractions remained unaltered. We conclude that a daily glass of red wine for 3 weeks significantly reduces plasma viscosity. Fibrinogen concentrations are also significantly reduced, when preceded by an abstention period. The decreased viscosity levels are maintained after 3 weeks of abstention, suggesting a sustained viscosity lowering effect of red wine.

Influence of freeze-drying on the clotting properties of fibrinogen in plasma.

Freeze-dried plasma standards are often used to calibrate fibrinogen assays. Little is known, however, about the effect of freeze-drying on the clotting properties of fibrinogen. If these properties are altered, the use of freeze-dried calibration standards might influence the results obtained when applying clotting assays to determine fibrinogen concentrations. In order to disclose any discrepancies in fibrinogen concentrations before and after freeze-drying, we determined the fibrinogen concentrations in citrated plasma samples using a total clottable protein method and a clotting-rate assay before and after freeze-drying. When using the clotting-rate assay, significantly higher fibrinogen concentrations were found in fresh-frozen plasma samples compared to freeze-dried samples (P<.001). In freeze-dried plasma samples, the fibrinogen concentrations were significantly higher using the total clottable protein assay than the clotting-rate assay (P<.001). When measuring the fibrinogen concentrations in plasma samples with a wide range of fibrinogen concentrations using the routinely employed clotting-rate assay, significantly higher fibrinogen concentrations were found using the freeze-dried calibration plasma, than the fresh-frozen calibration plasma (P=.02). We conclude that the clotting rate of fibrinogen in citrated plasma is reduced following freeze-drying. When using freeze-dried calibration plasma in a clotting-rate assay, higher fibrinogen concentrations are obtained than by using fresh-frozen plasma. Denaturation of fibrinogen during the freeze-drying process, affecting its polymerization properties, may constitute the main contributor to the reduced clotting rate of freeze-dried plasma.

The viscosity of fibrinogen subfractions and of EDTA denatured fibrinogen do not differ from that of native fibrinogen.

INTRODUCTION: Fibrinogen is a major determinant of plasma viscosity. The increased risk of atherothrombotic disease associated with a high fibrinogen concentration may partly be attributed to its effect on viscosity. Since the ratio between the three main fibrinogen subfractions high molecular weight (HMW)-, low molecular weight (LMW)-, and very low molecular weight (LMW')-fibrinogen is altered during acute phase conditions, and an increased HMW/LMW-fibrinogen ratio is associated with increased thromboembolic risk, we have examined how these subfractions affect viscosity. The viscosity of plasma is usually determined in ethylenediaminetetra-acetic acid (EDTA) plasma at 37 degrees C. Under such conditions the clotting properties of fibrinogen is affected due to denaturation. Denaturation of plasma proteins may affect their viscosity. Therefore, we have also investigated the effects of EDTA on the viscosity of fibrinogen. MATERIALS AND METHODS: Purified fibrinogen was obtained by beta-alanine precipitation of plasma from healthy donors. Separation of the fibrinogen fractions was performed by gradual precipitation of purified fibrinogen by ammonium sulphate. The viscosity was determined using a Haake Microvisco 2 viscometer. RESULTS: There was no statistically significant difference between the viscosity of native fibrinogen and the three fibrinogen subfractions. A substantial prolongation of the thrombin clotting time was observed in the fibrinogen solution containing EDTA at 37 degrees C compared to 20 degrees C. However, the viscosity of EDTA anticoagulated purified fibrinogen and plasma samples did not differ from that of heparin anticoagulated samples. CONCLUSION: The viscosity of the main fibrinogen subfractions HMW-, LMW- and LMW-fibrinogen did not differ from that of native fibrinogen, and the use of EDTA as anticoagulant did not significantly affect the viscosity of fibrinogen at 37 degrees C.

The obstructive siblings: Relapsing polychondritis without chondritis?

Progressive narrowing of the central airways due to diffuse inflammation is a potential life-threatening condition. A number of diseases have been described as possible causes. We present two siblings with severe central airway obstruction. Despite considerable efforts we have not been able to match the clinical appearance of our patients with the diagnostic criteria of any of the disease entities known to cause this condition.

High prevalence of respiratory symptoms during air travel in patients with COPD.

OBJECTIVE: The reduced pressure in aircraft cabins may cause severe hypoxemia and respiratory distress in patients with chronic obstructive pulmonary disease (COPD). The primary objective of this study was to determine the prevalence of in-flight symptoms in COPD patients and non-COPD subjects, and evaluate associations between these symptoms and pre-flight variables. METHODS: In a cross-sectional study of 391 COPD patients and 184 non-COPD subjects, we recorded lung function, blood gas values, exercise capacity, air travel habits and in-flight symptoms. RESULTS: Fifty-four percent of the COPD patients had travelled by air the last two years. Hypoxia-related symptoms during air travel were experienced in 25% of the COPD patients and 9% of the non-COPD subjects (p < 0.001). After adjusting for smoking status, age and gender, the odds ratio for COPD patients to experience dyspnea or air hunger was 6.6 (95% CI 2.5-17.3, p < 0.001) compared to non-COPD subjects. In the COPD patients, in-flight dyspnea or air hunger was strongly associated with pre-flight score on the Medical Research Council (MRC) Dyspnea scale (p < 0.001). CONCLUSION: COPD patients had significantly increased risk of in-flight dyspnea or air hunger compared to non-COPD subjects. In COPD patients these symptoms were strongly associated with pre-flight MRC Dyspnea score.

COPD and air travel: oxygen equipment and preflight titration of supplemental oxygen.

BACKGROUND: Patients with COPD may need supplemental oxygen during air travel to avoid development of severe hypoxemia. The current study evaluated whether the hypoxia-altitude simulation test (HAST), in which patients breathe 15.1% oxygen simulating aircraft conditions, can be used to establish the optimal dose of supplemental oxygen. Also, the various types of oxygen-delivery equipment allowed for air travel were compared. METHODS: In a randomized crossover trial, 16 patients with COPD were exposed to alveolar hypoxia: in a hypobaric chamber (HC) at 2,438 m (8,000 ft) and with a HAST. During both tests, supplemental oxygen was given by nasal cannula (NC) with (1) continuous flow, (2) an oxygen-conserving device, and (3) a portable oxygen concentrator (POC). RESULTS: PaO(2) kPa (mm Hg) while in the HC and during the HAST with supplemental oxygen at 2 L/min (pulse setting 2) on devices 1 to 3 was (1) 8.6 ± 1.0 (65 ± 8) vs 12.5 ± 2.4 (94 ± 18) (P < .001), (2) 8.6 ± 1.6 (64 ± 12) vs 9.7 ± 1.5 (73 ± 11) (P < .001), and (3) 7.7 ± 0.9 (58 ± 7) vs 8.2 ± 1.1 (62 ± 8) (P= .003), respectively. CONCLUSIONS: The HAST may be used to identify patients needing supplemental oxygen during air travel. However, oxygen titration using an NC during a HAST causes accumulation of oxygen within the facemask and underestimates the oxygen dose required. When comparing the various types of oxygen-delivery equipment in an HC at 2,438 m (8,000 ft), compressed gaseous oxygen with continuous flow or with an oxygen-conserving device resulted in the same PaO(2), whereas a POC showed significantly lower PaO(2) values. TRIAL REGISTRY: ClinicalTrials.gov; No.: Identifier: NCT01019538; URL: clinicaltrials.gov.