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Total blood carbon monoxide (TBCO) showed promising results in improving accuracy of CO determinations in blood and presenting better stability to different storage conditions. Therefore, it was proposed as an alternative biomarker to carboxyhemoglobin (COHb) for CO poisoning diagnosis. However, given that current interpretation reference values exist for COHb only, it is difficult to implement TBCO analysis in routine. Therefore, we aimed at determining TBCO reference values for postmortem CO poisoning cases. A previously validated method for TBCO analysis via gas chromatography-mass spectrometry was applied to cardiac, peripheral, cranial and spleen blood samples collected from 92 autopsies. Autopsy cases included 21 non-CO-related and 71 CO-related cases with varying postmortem intervals (PMIs). Statistical analyses were performed using statistical software R Studio. When comparing lower to higher PMIs for non-CO-related cases, no significant differences were found, which suggests that CO formation or degradation at low PMIs does not occur. Spleen blood showed potential as an alternative matrix to CO determinations in cases with sample availability issues but needs to be evaluated for CO-positive cases. Results for cardiac blood in CO-related autopsies showed a positive correlation between COHb and TBCO values (R = 0.78). This value is lower than what is found in the literature, suggesting that even though COHb and TBCO are correlated, a potential underestimation of the true CO exposure might occur if only COHb values are taken into consideration. Samples were divided into CO exposure groups based on COHb concentrations, and with the data obtained, classification into the following TBCO concentration groups is proposed: no significant CO exposure case <6 µmol/mL, medium CO exposure case 6-20 µmol/mL and high CO exposure case >20 µmol/mL. Even if a higher number of samples in each group would enable to increase the confidence, these results are very promising and highlight the importance of TBCO measurement., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

There are 2 techniques for detecting red blood cell survival (RBCS) detection techniques: red blood cell labeling test and carbon monoxide (CO) breath test. The former has disadvantages such as long measurement times and complicated procedures, while the latter is simple, convenient, moderately priced, and capable of dynamically monitoring changes in RBCS before and after treatment. Currently, the CO breath test is gradually being implemented in clinical practice. RBCS is not only applied to hematologic diseases such as multiple myeloma, myelodysplastic syndromes, lymphoma, and thalassemia, but also to non-hematologic diseases like type 2 diabetes and chronic kidney disease. It can assist in diagnosis, guide treatment, evaluate drug treatment efficacy, and predict disease progression.

Carboxyhemoglobin (COHb) is an index of endogenous carbon monoxide formation during the hem degradation process and could be used to confirm hemolysis in neonates. The influence of other clinical factors on COHb values in neonates has not been fully investigated. We aimed to evaluate the influence of hemolysis, sepsis, respiratory distress, and postnatal age on COHb values. We retrospectively analyzed COHb measurements determined with a carbon monoxide-oximeter in 4 groups of term neonates: A-sepsis, B-respiratory distress, C-hemolysis, and D-healthy neonates. The mean COHb values were 1.41% (SD: 0.26), 1.32% (SD: 0.27), 2.5% (SD: 0.69), and 1.27% (SD: 0.19) (P<0.001) in groups A (n=8), B (n=37), C (n=16), and D (n=76), respectively. COHb in group C was significantly higher than in the other groups. There was a negative correlation between postnatal age and COHb in healthy neonates. A cut-off level of 1.7% had 93% (95% confidence interval [CI]: 89%-97%) sensitivity and 94% (95% CI: 90%-98%) specificity for diagnosis of hemolysis. COHb values were higher during the first days of life. We found that COHb levels in neonates with hemolysis were significantly higher and that the influence of sepsis and respiratory distress on COHb values was insignificant., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Patients recovering from coronavirus disease 2019 (COVID-19) may not return to a pre-COVID functional status and baseline levels of healthcare needs after discharge from acute care hospitals. Since the long-term outcomes of COVID-19 can be more severe in patients with underlying cardiorespiratory diseases, we aimed at verifying the impact of a preexisting cardiorespiratory comorbidity on multidisciplinary rehabilitation in post-COVID-19 patients. We enrolled 95 consecutive patients referring to the Pulmonary Rehabilitation Unit of Istituti Clinici Scientifici Maugeri Spa SB, IRCCS of Telese Terme, Benevento, Italy after being discharged from the COVID-19 acute care ward and after recovering from acute COVID-19 pneumonia. Forty-nine of them were not suffering from underlying comorbidities, while 46 had a preexisting cardiorespiratory disease. Rehabilitation induced statistically significant improvements in respiratory function, blood gases and the ability to exercise both in patients without any preexisting comorbidities and in those with an underlying cardiorespiratory disease. Response to the rehabilitation cycle tended to be greater in those without preexisting comorbidities, but DLco%-predicted was the only parameter that showed a significant greater improvement when compared to the response in the group of patients with underlying cardiorespiratory comorbidity. This study suggests that multidisciplinary rehabilitation may be useful in post-COVID-19 patients regardless of the presence of preexisting cardiorespiratory comorbidities., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the contributing risk factors for polycythemia in COPD have not been extensively studied., Methods: We analyzed the presence of secondary polycythemia in current and former smokers with moderate to very severe COPD at the five-year follow-up visit in the observational COPDGene study. We used logistic regression to evaluate the association of polycythemia with age, sex, race, altitude, current smoking status, spirometry, diffusing capacity for carbon monoxide (DLCO), quantitative chest CT measurements (including emphysema, airway wall thickness, and pulmonary artery to aorta diameter ratio), resting hypoxemia, exercise-induced hypoxemia, and long-term oxygen therapy., Results: In a total of 1928 COPDGene participants with moderate to very severe COPD, secondary polycythemia was found in 97 (9.2%) male and 31 (3.5%) female participants. In a multivariable logistic model, severe resting hypoxemia (OR 3.50, 95% CI 1.41-8.66), impaired DLCO (OR 1.28 for each 10-percent decrease in DLCO % predicted, CI 1.09-1.49), male sex (OR 3.60, CI 2.20-5.90), non-Hispanic white race (OR 3.33, CI 1.71-6.50), current smoking (OR 2.55, CI 1.49-4.38), and enrollment in the Denver clinical center (OR 4.42, CI 2.38-8.21) were associated with higher risk for polycythemia. In addition, continuous (OR 0.13, CI 0.05-0.35) and nocturnal (OR 0.46, CI 0.21-0.97) supplemental oxygen were associated with lower risk for polycythemia. Results were similar after excluding participants with anemia and participants enrolled at the Denver clinical center., Conclusions: In a large cohort of individuals with moderate to very severe COPD, male sex, current smoking, enrollment at the Denver clinical center, impaired DLCO, and severe hypoxemia were associated with increased risk for secondary polycythemia. Continuous or nocturnal supplemental oxygen use were associated with decreased risk for polycythemia., (© 2021. The Author(s).)

Background: Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear., Methods: We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies., Results: We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were - 34.4 and - 112.2 mL (p = 0.168) in forced vital capacity (FVC), and - 0.53 and - 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DL CO ) in the autoantibody-negative and autoantibody-positive groups, respectively., Conclusions: Reductions in FVC and DL CO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

Gasotrasmitters are endogenously synthesized gaseous molecules that are engaged in cellular physiological and pathological processes. Stress influences various physiological aspects of an organism and amends a normal system's functions, including those of the reproductive system. This study aims to investigate the effect of long-term exposure to restraint stress on the male reproductive system as well as the possible impact of stress on the levels of nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H 2 S), and the expression of their producing-enzymes. In this study, rats were subjected to the restraint condition for 2 h per day and 7 days per week for 8 consecutive weeks. The results revealed decreases in the serum levels of kisspeptin-1(Kiss-1), gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and dehydroepiandrosterone sulfate (DHEA-s); however, corticosterone, gonadotropin-inhibitory hormone (GnIH), estradiol (E2) and prolactin levels increased following restraint stress. The mRNA expression levels of NO synthases (NOSs); neuronal NOS (nNOS), inducible NOS (iNOS) and H 2 S synthases; cystathionine-γ-lyase- (CSE), 3-mercaptopyruvate-sulfurtransferase- (3MST) and CO-producing enzyme; heme oxygenase-2 (HO-2) were upregulated in the hypothalamus of restraint rats. Testicular mRNA expression levels of endothelial NOS (eNOS), nNOS, HO-1 and HO-2 were upregulated whereas cystathionine β-synthase (CBS), CSE and 3MST expression levels were downregulated following restraint stress. Concentrations of NO increased in the testes but decreased in the semen of restraint rats. On the contrary, CO levels were reduced in the testes while they were elevated in the semen, whereas H 2 S concentrations decreased in both testes and semen of restraint rats. Concentrations of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), as well as total antioxidant capacity (TAC) rose in the testes, while they declined in the semen of the restraint group. Restraint stress decreases the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the testes while increasing them in the semen. Collectively, restraint stress negatively impacts male reproductive functions and modulates gasotransmitters producing-enzymes expression in the hypothalamus and testes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits., Study Design: Prospective experimental study., Animals: A total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation)., Methods: Rabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg -1 ) and midazolam (0.5 mg kg -1 ). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 μg kg -1 minute -1 ; medium, 0.5 μg kg -1 minute -1 ; and high doses, 1 μg kg -1 minute -1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey's post hoc comparison was performed (p < 0.05)., Results: Significant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments., Conclusions and Clinical Relevance: The infusion of NE at 0.5-1.0 μg kg -1 minute -1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

We measured end-tidal CO levels in 50 jaundiced newborns readmitted for phototherapy at age 54-244 hours. The median end-tidal CO level was 1.55 ppm, suggesting that hemolysis is not the primary contributor to the hyperbilirubinemia in many readmitted newborns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Total hemoglobin mass (Hb mass ) is routinely assessed in studies by the carbon monoxide (CO) rebreathing. Its clinical application is often hindered due to the consequent rise in carboxyhemoglobin (%HbCO) and the concern of CO toxicity. We tested the reproducibility of the CO rebreathing with a CO dose of 0.5 mL/kg body mass (CO 0.5 ) compared to 1.5 mL/kg (CO 1.5 ) and when shortening the CO rebreathing protocol. Therefore, CO rebreathing was performed 1×/day in eight healthy individuals on four consecutive days. On each day, either CO 0.5 (CO 0.5 -1 and CO 0.5 -2) or CO 1.5 (CO 1.5 -1 and CO 1.5 -2) was administered. Venous blood samples to determine %HbCO and quantify Hb mass were obtained prior to, and at 6 (T 6 ), 8 (T 8 ) and 10 min (T 10 ) of CO rebreathing. This protocol was tested at sea level and at 2320 m to investigate the altitude-related measurement error. At sea level, the mean difference (95% limits of agreement) in Hb mass between CO 0.5 -1 and CO 0.5 -2 was 26 g (-26; 79 g) and between CO 1.5 -1 and CO 1.5 -2, it was 17 g (-18; 52 g) . The respective typical error (TE) corresponded to 2.4% (CO 0.5 ) and 1.5% (CO 1.5 ), while it was 6.5% and 3.0% at 2320 m. With CO 0.5 , shortening the CO rebreathing resulted in a TE for Hb mass of 4.4% (T 8 vs. T 10 ) and 14.1% (T 6 vs T 10 ) and with CO 1.5 , TE was 1.6% and 5.8%. In conclusion, the CO dose and rebreathing time for the CO rebreathing procedure can be decreased at the cost of a measurement error ranging from 1.5-14.1%.

Introduction: Carbon-monoxide (CO) is a major component of motor-vehicles related air pollution. Motor-vehicles emissions are a major source of air pollution in urban areas and give significant adverse effects on human life., Aim: This study aimed to assess the change of expiratory carbon-monoxide levels after using four-type of masks in people around Universitas Sumatera Utara., Methods: This was an experimental study with a consecutive sampling technique involved 100 non-smoker subjects. They were divided into four groups based on masks given: fabric, surgical, carbon, and an N95 mask. Expiratory CO was measured by a smokerlyzer device. Data were analyzed using SPSS software with Wilcoxon and Kruskal Wallis Test., Results: There was a significant change of carbon-monoxide mean level after using the mask for 8 hours in a surgical mask, N95 mask, and carbon mask (p-value: 0.002; 0.000; 0.000). After analyzed using Kruskal Wallis Test, there was a significant difference in the change of mean of pre and post wearing mask (ΔCO) among four-type of masks with p-value < 0.001. Post Hoc Analysis showed the significant difference was in the comparison between N95 mask vs Fabric Mask and Carbon Mask vs Fabric Mask (p-value: 0.002; 0.021)., Conclusion: All three type of masks such as surgical mask, N95 mask, and carbon mask was effective to reduce CO levels from air pollution with the most significant was N95 and carbon mask. Fabric mask has the poorest protection from CO levels., Competing Interests: There are no conflicts of interest., (© 2020 Noni Novisari Soeroso, Tengku Kemala Intan, M. Ichwan, M. Hanif Fadlurrahman, Fannie Rizki Ananda.)

The recently published Global Lung Function Initiative (GLI) carbon monoxide transfer factor ( T LCO ) reference equations provide an opportunity to adopt a current, all-age, widely applicable reference set. The aim of this study was to document the effect of changing to GLI from commonly utilised reference equations on the interpretation of T LCO results.33 863 T LCO results (48% female, 88% Caucasian, n=930 aged <18 years) from clinical pulmonary function laboratories within three Australian teaching hospitals were analysed. The lower limit of normal (LLN) and proportion of patients with a T LCO below this value were calculated using GLI and other commonly used reference equations.The average T LCO LLN for GLI was similar or lower than the other equations, with the largest difference seen for Crapo equations (median: -1.25, IQR: -1.64, -0.86 mmol·min -1 ·kPa -1 ). These differences resulted in altered rates of reduced T LCO for GLI particularly for adults (+1.9% versus Miller to -27.6% versus Crapo), more so than for children (-0.8% versus Kim to -14.2% versus Cotes). For adults, the highest raw agreement for GLI was with Miller equations (94.7%), while for children it was with Kim equations (98.1%). Results were reclassified from abnormal to normal more frequently for younger adults, and for adult females, particularly when moving from Roca to GLI equations (30% of females versus 16% of males).The adoption of GLI T LCO reference equations in adults will result in altered interpretation depending on the equations previously used and to a greater extent in adult females. The effect on interpretation in children is less significant., Competing Interests: Conflict of interest: D.J. Brazzale has nothing to disclose. Conflict of interest: L.M. Seccombe has nothing to disclose. Conflict of interest: L. Welsh has nothing to disclose. Conflict of interest: C.J. Lanteri has nothing to disclose. Conflict of interest: C.S. Farah has nothing to disclose. Conflict of interest: W.R. Ruehland has nothing to disclose., (Copyright ©ERS 2020.)

Introduction: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients., Methods: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival., Results: Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide ( D LCO ) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV 1 )/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort., Conclusion: Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV 1 /FVC ratio was identified as an independent risk factor for worsened outcomes., Competing Interests: Conflict of interest: O.A. Shlobin reports personal fees for consultancy from United Therapeutics, Bayer and Johnson & Johnson, outside the submitted work. Conflict of interest: V. Kouranos has nothing to disclose. Conflict of interest: S.D. Barnett has nothing to disclose. Conflict of interest: E.H. Alhamad has nothing to disclose. Conflict of interest: D.A. Culver reports institutional funding for the registry from Gilead, during the conduct of the study; personal fees for advisory board work from Johnson and Johnson, outside the submitted work. Conflict of interest: J. Barney has nothing to disclose. Conflict of interest: F.C. Cordova has nothing to disclose. Conflict of interest: E.M. Carmona reports financial support for the clinical trial from Gilead, during the conduct of the study; personal fees for consultancy and developing education materials from CHEST, personal fees for editorial work from Elsevier, outside the submitted work. Conflict of interest: M.B. Scholand has performed advisory board work and been investigator in clinical trials for Boehringer Ingelheim and Genentech, and been investigator in clinical trials for Fibrogen and Global Blood Therapeutics, outside the submitted work; and has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued. Conflict of interest: M. Wijsenbeek has nothing to disclose. Conflict of interest: S. Ganesh has nothing to disclose. Conflict of interest: E.E. Lower reports grants from Gilead, Bayer and Genentech, during the conduct of the study. Conflict of interest: P.J. Engel has nothing to disclose. Conflict of interest: J. Wort reports grants and personal fees from Actelion Pharmaceuticals and Bayer Pharmaceuticals, personal fees from MSD, outside the submitted work. Conflict of interest: L. Price reports personal fees and education support from Actelion and Johnson & Johnson, during the conduct of the study. Conflict of interest: A.U. Wells reports personal fees from Boehringer Ingelheim, Roche, Intermune and Bayer, outside the submitted work. Conflict of interest: S.D. Nathan reports personal fees for consultancy from United Therapeutics, Bayer Pharmaceuticals, Bellerophon and Actelion, during the conduct of the study. Conflict of interest: R.P. Baughman reports grants from Gilead, Bayer, Genentech, Foundation for Sarcoidosis Research and National Institutes of Health, grants and personal fees for consultancy from Actelion, grants and personal fees for consultancy and lectures from Mallinckrodt, during the conduct of the study., (Copyright ©ERS 2020.)

Background: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone., Methods: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects., Results: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups., Conclusion: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

Concentrations of 64% to 70% nitrous oxide (N 2 O) provide intra-operative analgesia. Clinically, pulse oximeter estimation (SpO 2 ) of oxygen (O 2 ) hemoglobin saturation (SaO 2 ) was observed to decrease with N 2 O. Absorption atelectasis from breathing O 2 was thought to decrease arterial partial pressure of O 2 (PaO 2 ) below 70 mmHg and reduce SaO 2 and SpO 2 when N 2 O was used. Administering N 2 O from the beginning of the anesthesia might prevent atelectasis development and low PaO 2 . The study was done in 2 parts ( P < 0.05). In Part 1, isoflurane-anesthetized dogs undergoing ovariohysterectomy ( n = 15 each group) breathed N 2 O from anesthesia start (N 2 O early ) or 1 hour later (N 2 O late ). SpO 2 , CO-oximetry values, and PaO 2 were compared to dogs breathing O 2 throughout anesthesia (control). Timing of N 2 O introduction did not affect PaO 2 (lowest = 94 mmHg), SaO 2 , or SpO 2 . With N 2 O, the lowest SpO 2 value was 91% and corresponded to a PaO 2 of 151 mmHg. Carboxyhemoglobin increased (highest = 2.7%) and SaO 2 decreased with N 2 O (lowest = 96.7%). In Part 2, to replicate findings, 10 isoflurane-anesthetized dogs breathed N 2 O, then O 2 . With N 2 O, SaO 2 did not decrease, but carboxyhemoglobin increased and returned to baseline once N 2 O was discontinued. The dog with the highest carboxyhemoglobin (2%) had an SaO 2 of 96.8% (PaO 2 = 93 mmHg). Carboxyhemoglobin and SaO 2 changes were not clinically significant. Pulse oximetry did not reliably estimate SaO 2 but N 2 O was not always a factor., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Objective: The aim of our study is to determine whether there is a change in the plasma levels of copeptin and there is a relationship among the plasma levels of carboxyhemoglobin (COHb), lactate, and copeptin levels in patients presenting to the emergency department with carbon monoxide (CO) poisoning., Methods: Fifty-seven patients admitted to the emergency department with CO poisoning were included in the study. The blood samples of the patients were collected on arrival 0th, 6th, and 12th hours for copeptin, lactate, and COHb levels. Data were analyzed using SPSS-17 statistical software., Results: Arrival serum copeptin levels of the patients were compared to copeptin levels of healthy individuals and a statistically significant difference was found between them ( p = 0.008). There was a statistically significant difference between the arrival levels of copeptin and 6th-hour ( p = 0.006) and 12th-hour ( p = 0.001) levels of copeptin. There was no significant difference between 6th-hour and 12th-hour copeptin levels ( p = 0.51). In terms of serum lactate levels, there was a significant difference between arrival and 6th h ( p < 0.001), arrival and 12th h ( p < 0.001), and 6th and 12th h ( p < 0.001). Likewise, in terms of serum COHb levels, there was a significant difference between arrival and 6th h ( p < 0.001), arrival and 12th h ( p < 0.001), and 6th and 12th h ( p < 0.001). There was a positive correlation between COHb and lactate levels on arrival ( r = 0.52; p = 0.001)., Conclusion: Copeptin as a stress hormone can be used in the diagnosis and monitoring of patients with CO poisoning. However, the copeptin level was not superior to COHb and lactate levels.

The determination of carbon monoxide (CO) and carboxyhemoglobin (COHb) is of utmost importance in forensic toxicology to determine the cause of death in cases of CO poisoning, fire, and explosions. To this end, reliable and updated analytical methods are required. In this paper, four different methods for the determination of carbon monoxide in postmortem blood samples were compared: (i) the spectrophotometric determination of COHb applying the method proposed by Rodkey and modified by Beutler-West, (ii) the spectrophotometric determination of CO using a micro-diffusion-based method, (iii) the determination of CO by gas chromatography coupled to a TCD detector, and (iv) the determination of COHb by blood gas analysis. Three postmortem blood samples were analyzed with all methods, and the results were comparable. The applied methodologies showed different features depending on the sensitivity, sample preparation, and volume. The HS-GC/TCD method in our hand was the most appropriate, on postmortem samples, and versatile to apply. Unfortunately, only a limited number of postmortem blood samples were available for this study due to the rarity of that kind of intoxication in our jurisdiction., (© 2019 American Academy of Forensic Sciences.)

Background: Carbon monoxide (CO) poisoning is an important public health issue around the world. Research indicates that many factors may be related to the rate of CO uptake and elimination in the human body. However, some factors related to CO uptake and elimination are considered controversial. Relatively little attention has been devoted to review and synthesis of factors affecting CO uptake and elimination., Purpose: This paper provides a critical scoping review of the factors and divides them into four aspects, including environmental, demographic, physiological and treatment factors., Methods: We searched the scientific databases for research that has proposed a mathematical equation as a synthesis of quantities related to CO poisoning, CO elimination, CO uptake, CO half-life, CO uptake and elimination and their relationships. After excluding the studies that did not meet the study criteria, there were 39 studies included in the review and the search was completed before 16 December 2019., Results and Conclusion: This review discusses most of the factors that impact the rate of CO uptake and elimination. Several factors may be related to CO uptake and elimination, such as CO concentration, the duration of exposure to CO, age, sex, exercise, minute ventilation, alveolar ventilation, total haemoglobin mass and different treatments for CO poisoning. Although some potential factors were not included in the review, the findings are useful by presenting an overview for discussing factors affecting CO uptake and elimination and provide a starting point for further study regarding strategies for CO poisoning and the environmental standard of CO., Competing Interests: Funding: This research was conducted as part of K-TP’s PhD studies at UCL supported by a grant from the Taiwanese government.

Diagnosis of carbon monoxide (CO) poisonings has always been a challenging task due to the susceptibility to alterations of the optical state and degradation of blood samples during sampling, transport and storage, which highly affects the analysis with spectrophotometric methods. Methodological improvements are then required urgently because of increased reports of cases with discrepancies between results of the measured biomarker carboxyhemoglobin (COHb) and reported symptoms. Total blood CO (TBCO) measured chromatographically was thus proposed in a previous study as alternative biomarker to COHb. This approach was investigated in this study by comparing the two biomarkers and assessing the effects of various storage parameters (temperature, preservative, time, tube headspace (HS) volume, initial saturation level, freeze- and thaw- and reopening-cycles) over a period of one month. Results show that while for TBCO, concentrations are relatively stable over the observation period regardless of parameters such as temperature, time and HS volume, for COHb, concentrations are altered significantly during storage. Therefore, the use of TBCO as alternative biomarker for CO poisonings has been proposed, since it provides more valid results and is more stable even under non-optimal storage conditions. Additionally, it can be used to predict COHb in cases where sample degradation hinders optical measurement. Furthermore, a correction formula for COHb and TBCO is provided to be used in laboratories or circumstances where optimal storage or analysis is not possible, to obtain more accurate results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

New Findings: What is the central question of this study? Is it necessary to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in patients with chronic mountain sickness? What is the main finding and its importance? The CO-rebreathing method must be modified because of the prolonged CO-mixing time in patients with chronic mountain sickness. After adaptation of the blood sampling method, reliable and valid results were attained. With this modification, it is possible to quantify the extent of polycythaemia and to distinguish between a haemoconcentration and an exclusive enhancement of erythrocyte volume., Abstract: Patients suffering from chronic mountain sickness (CMS) exhibit extremely high haemoglobin concentrations. Their haemoglobin mass (Hbmass), however, has rarely been investigated. The CO-rebreathing protocol for Hbmass determination in those patients might need to be modified because of restricted peripheral perfusion. The aim of this study was to evaluate the CO uptake and carboxyhaemoglobin-mixing time in the blood of CMS patients and to adapt the CO-rebreathing method for this group. Twenty-five male CMS patients living at elevations between 3600 and 4100 m above sea level were compared with ethnically matched healthy control subjects from identical elevations (n = 11) and near sea level (n = 9) and with a Caucasian group from sea level (n = 6). CO rebreathing was performed for 2 min, and blood samples were taken for the subsequent 30 min. After the method was modified, its reliability was evaluated in test-retest experiments (n = 28), and validity was investigated by measuring the Hbmass before and after the phlebotomy of 500 ml (n = 4). CO uptake was not affected by CMS. The carboxyhaemoglobin mixing was completed after 8 min in the Caucasian group but after 14 min in the groups living at altitude. When blood was sampled 14-20 min after inhalation, the typical error of the method was 1.6% (confidence limits 1.2-2.5%). After phlebotomy, Hbmass decreased from 1779 ± 123 to 1650 ± 129 g, and no difference was found between the measured and calculated Hbmass (1666 ± 122 g). When the time of blood sampling was adapted to accommodate a prolonged carboxyhaemoglobin-mixing time, the CO-rebreathing method became a reliable and valid tool to determine Hbmass in CMS patients., (© 2019 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: Several serum markers were reported to reflect the severity of pulmonary alveolar proteinosis (PAP). The aim of this study is to investigate a reliable and facile marker to access and monitor the clinical course of PAP in a large cohort., Methods: PAP patients from January 2010 to June 2018 were enrolled. Hospital records were used as data sources. The levels of various serum indicators were detected. We evaluated the correlation between pulmonary function test results and clinical variables., Results: Diffusion capacity for carbon monoxide (DLCO) level was positively correlated with the level of high-density lipoprotein cholesterol (HDL-C) ( P < 0.05) in 122 patients of PAP at baseline. The levels of HDL-C and DLCO significantly increased while carcinoembryonic antigen (CEA), CYFRA21-1, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH) levels decreased six months after granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy between 14 patients with PAP. Nevertheless, the increased DLCO was significantly correlated with decreased CEA ( r = -0.579, P = 0.031) and CYFRA 21-1 ( r = -0.632, P = 0.015). In 10 PAP patients without GM-CSF inhalation therapy, HDL-C and DLCO significantly decreased while NSE and LDH levels increased after six months of follow-up. The decreased DLCO was significantly correlated with increased LDH ( r = -0.694, P = 0.026)., Conclusions: Serum CEA, CYFRA21-1, and LDH are valuable serum markers for the evaluation of disease activity of PAP and may predict the response to treatment of PAP., Competing Interests: The authors declare that there is neither conflict of interest nor financial gain regarding the publication of this paper., (Copyright © 2019 Shenyun Shi et al.)

The present work simulates the transport of oxygen, carbon dioxide, and carbon monoxide between a fetus's circulatory system and the mother's. The organ responsible for this exchange is the placenta. Carbon monoxide is a common air pollutant, and it impacts the physiological conditions even in low concentration. The impacts of carbon monoxide are especially dangerous for pregnant women, fetuses, and newborn babies. A model of carbon monoxide transport, from the literature, is modified to simulate a pregnant woman (original model was a male), therefore changing some parameters to express the adjusted respiratory system. It was considered the gas exchange in the placenta, to evaluate the concentration of these different gases in the fetus arterial and venous blood. Three methods of the exergy analysis are implemented for both mother and fetus respiratory systems, aiming at the comparison with the respiratory system of a male adult. The destroyed exergy of the literature did not have the same trend as the models proposed in this article, taking into consideration the hemoglobin reactions. In contrast, the entropy generation associated only with the diffusion transport phenomena was one order of magnitude lower than the other methods. The placenta destroyed exergy rate is significantly higher compared to the irreversibilities of the mother's respiratory system. One possible explanation is the fact that the placenta has other physiological functions than gas transportation.

Background: To investigate the role of fetuin-A as a potential biomarker for prognosis of fatality in patients with carbon monoxide (CO) poisoning., Methods: In a prospective study, 60 poisoned patients with CO who were admitted to the department of emergency medicine between August 2017 and April 2018 were compared to 40 paired control subjects from the same department., Results: Fetuin-A levels were significantly lower in the patients with CO poisoning, especially in those non-survive (68.9 ± 7.6 vs 59.5 ± 4.1, p = 0.019). The area under the curve in the ROC curve analysis for the fetuin-A was 0.914 with a cut off of 61.15 mmol/L., Conclusions: The decrease of Fetuin-A may indicate an early signal for the progression of fatality due to CO poisoning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: Carbon monoxide is one of the most common causes of fatal intoxications in the United States, and multiple previous studies have demonstrated that cigarette smokers have higher levels of carbon monoxide in their blood. However, the potential negative effects due to acute carbon monoxide poisoning from excessive cigarette smoking have not been well established., Methods: This is a single patient case report., Results: In this case report, a 40-year-old male with a past medical history of depression, anxiety, panic attacks, and substance use disorder developed symptomatic, acute carbon monoxide poisoning secondary to heavy cigarette smoking in a confined space. In this patient, the cessation of clonazepam therapy coincided with increasing anxiety and panic disorder with agoraphobia triggering an escalation in his cigarette smoking. The patient smoked three packs of cigarettes in 3 hours and developed worsening of his symptoms. He required inpatient treatment with benzodiazepines and hyperbaric oxygen., Discussion and Conclusions: Therefore, it is important to recognize cigarette smoke as a significant source of carbon monoxide exposure., Scientific Significance: While the negative effects of cigarette smoking are often perceived as being chronic and only coming to fruition after numerous years of exposure, it is important for both physicians and patients to recognize the possibility for potentially life-threatening acute toxicity secondary to carbon monoxide exposure. (Am J Addict 2019;28:413-415)., (© 2019 American Academy of Addiction Psychiatry.)

Background and Objectives: Recent surveys confirm continued increases in the use of electronic-cigarettes (e-cigarettes) in adolescents and adults. Users often state that e-cigarettes reduce tobacco craving and withdrawal symptoms in addition to their smoking. Data from laboratory studies and clinical trials have confirmed these statements, though there are inconsistencies in the outcomes. In this pilot study, we set out to evaluate the effects of e-cigarettes, as compared to the participants' own cigarettes, on baseline craving and smoking severity., Methods: Using a within-subjects, placebo-controlled study design, 15 tobacco-dependent, e-cigarette naïve participants sustained abstinence overnight. They completed distinct phases of this protocol during four separate study sessions. Participants were randomized to an e-cigarette device containing one of three doses of nicotine (0, 18, or 36 mg/ml) or their own cigarette. Each study visit was ~3 hours long and separated by at least 7 days. Visits included assessments of craving and smoking severity., Results: The data showed that after 10 puffs in both the Own cigarette and e-cigarette conditions, breath carbon monoxide levels increased significantly in the former but not the latter. Questionnaire of Smoking Urges and Choices to Smoke scores were not statistically different across groups after two distinct bouts of 10 puffs each. Additionally, E-cigarette Perceptions Questionnaire responses were not significantly different according to dose., Conclusion and Scientific Significance: This experiment provides data demonstrating that e-cigarettes did not reduce craving or smoking severity in e-cigarette naïve users. However, since this was a pilot study, the conclusions that can be drawn are limited. (Am J Addict 2019;28:361-366)., (© 2019 American Academy of Addiction Psychiatry.)

Background: To assess the validity of central and pulmonary veno-arterial CO 2 gradients to predict fluid responsiveness and to guide fluid management during liver transplantation., Methods: In adult recipients (ASA III to IV) scheduled for liver transplantation, intraoperative fluid management was guided by pulse pressure variations (PPV). PPV of ≥15% (Fluid Responding Status-FRS) indicated fluid resuscitation with 250 ml albumin 5% boluses repeated as required to restore PPV to < 15% (Fluid non-Responding Status-FnRS). Simultaneous blood samples from central venous and pulmonary artery catheters (PAC) were sent to calculate central venous to arterial CO 2 gap [C(v-a) CO2 gap] and pulmonary venous to arterial CO 2 gap [Pulm(p-a) CO2 gap]. CO and lactate were also measured., Results: Sixty seven data points were recorded (20 FRS and 47 FnRS). The discriminative ability of central and pulmonary CO 2 gaps between the two states (FRS and FnRS) was poor with AUC of ROC of 0.698 and 0.570 respectively. Central CO 2 gap was significantly higher in FRS than FnRS (P = 0.016), with no difference in the pulmonary CO 2 gap between both states. The central and Pulmonary CO 2 gaps are weakly correlated to PPV [r = 0.291, (P = 0.017) and r = 0.367, (P = 0.002) respectively]. There was no correlation between both CO 2 gaps and both CO and lactate., Conclusion: Central and the Pulmonary CO 2 gaps cannot be used as valid tools to predict fluid responsiveness or to guide fluid management during liver transplantation. CO 2 gaps also do not correlate well with the changes in PPV or CO., Trial Registration: Clinicaltrials.gov Identifier: NCT03123172 . Registered on 31-march-2017.

The presented manuscript describes the carbon monoxide (CO) related deaths in Portugal over a period of 3 years, based on autopsies carried out at the National Institute of Legal Medicine and Forensic Sciences, from January 2012 to December 2014. Three hundred and forty-seven forensic autopsy reports with carboxyhaemoglobin (COHb) analysis requests were analysed and subdivided into three main groups: (1) improbable CO intoxication; (2) possible CO intoxication; (3) highly probable CO intoxication. In group 1, COHb analysis was negative, and the death circumstances, as well as the post mortem findings, didn't corroborate an exposition to CO. In group 2, with COHb positive in 1/3 of the cases, the death circumstances corroborated an exposition to CO, but the post mortem findings weren't enough to confirm an exposition to this substance. In group 3, the results of COHb were positive, and both circumstances of death and post mortem findings corroborated an exposition to CO. The first group (113 cases) had no specific suspicion of a CO intoxication and, thus, the request of a COHb analysis had no particular basis, reflected in the low COHb achieved percentage (between 0 and 12). In the second group (164 cases), 29% of the cases were directly or indirectly related to CO exposure (between 0% and 94%). In the third group (70 cases), 56 deaths were due to CO intoxication and 14 due to burns after CO inhalation (between 18% and 91%). This study intended to do, not only a 3-year assessment of CO poisoning, but also to enhance the fact that circumstantial information, as well as a correct evaluation at the forensic autopsy data are crucial, and allow an enhanced diagnosis of possible intoxication, as well as a better guidance for the consequent toxicological analysis requests., (Copyright © 2019. Published by Elsevier B.V.)

The goal of our study was to assess acute respiratory responses to using e-cigarettes in exclusive e-cigarette users (E-Group) and dual users (T/E-Group) and to compare these effects with responses to smoking tobacco-cigarettes in tobacco smokers (T-Group). The study included 120 adults (age: 21.7 ± 2.1 years) divided into 4 groups (n = 30 each): Controls, T-, E-, T/E-Group. Spirometric status, O 2 saturation, exhaled FeNO levels, exhaled CO levels, and airway temperature were assessed before the use of an e-cigarette (E-, T/E-Group) or tobacco cigarette as well as 'minute 1' and 'minute 30' after smoking. Controls used an e-cigarette without e-liquid. Lower (p < 0.05) baseline values of FeNO were found in T-Group (15.4 ppb) and in T/E-Group (15.0 ppb) than in Controls (19.6 ppb). Following exposure, and compared with Controls, T-, and T/E-Group had a significant decrease (p < 0.05) in PEF and MEF75. Mean FeNO values decreased on 'minute 1' in T-Group (by 2.1 ppb), E-Group (by 1.5 ppb) and in T/E-Group (by 2.2 ppb). Other effects included increase in temperature of exhaled air (p < 0.05). The use of e-cigarettes is associated with decreased FeNO and airflow indices (PEF, MEF75), but an increase in airway temperature. These changes are similar to those after exposure to tobacco cigarette smoke.

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 μmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 μmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We examine the ability of pre-existing measures of Forced Expiratory Volume in 1 s (FEV1), and Diffusion Capacity for Carbon Monoxide (DLCO) to determine the subsequent 30-day mortality outcome following unselected acute medical admission., Methods: Between 2002 and 2017, we studied all emergency medical admissions (106,586 episodes in 54,928 patients) of whom 8071 were classified as respiratory. We employed logisitic multiple variable regression models to evaluate the ability of FEV1 or DLCO to predict the 30-day hospital mortality outcome., Results: The 30-day hospital episode mortality outcome demonstrated curvilinear relationships to the underlying FEV1 or DLCO values; adjusted for major outcome predictors, a higher FEV1 - OR 0.85 (95% CI: 0.82, 0.89) or DLCO OR 0.76 (95% CI: 0.73, 0.79) values predicted survival. The range of predicted mortalities was from 3.3% (95% CI: 2.5, 4.0) to 23.5% (95% CI: 20.8, 26.2); the FEV1 (Model1) and DLCO (Model2) outcome prediction was essentially equivalent (Chi2 = 2.9: p = 0.08)., Conclusion: The 30-day mortality outcome was clearly related to the pre-admission FEV1 and DLCO value. The outcome relationship was curvilinear. Either parameter appears a useful tool to explore hospital outcomes. Previously suggested cut-points are likely an artefact and not supported by these data., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The production of erythropoietin (Epo) is modulated by renal tissue oxygen tension, which in principle depends on both arterial oxygen content (CaO2) and arterial oxygen tension (PaO2). Uncontrolled observational studies suggest that alterations in CaO2 fundamentally regulate Epo synthesis. We sought to establish whether reduced CaO2 enhances plasma Epo concentration independently of PaO 2 . In a blinded crossover study, 8 healthy young subjects were exposed to three conditions: room air (normoxia); 11% oxygen balanced in nitrogen, which lowers both CaO2 and PaO2 (hypoxia); and carbon monoxide plus normoxia, which decreases CaO2 to the same degree as hypoxia while preserving PaO2 (hypoxemia). Arterial blood samples were obtained prior to and throughout the 5 hours of exposure to each condition. In the hypoxic conditions, average CaO2 was reduced to similar levels, whereas PaO2 was only decreased with exposure to hypoxia. Plasma Epo concentration was increased in both hypoxic conditions relative to normoxia after 150 min of exposure and was augmented more than two-fold after 300 min, with no difference between hypoxic conditions. Reduced CaO2 induces similar increases in circulating Epo concentration irrespective of PaO2 manipulation, demonstrating that CaO2 is the critical variable regulating Epo production., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)