Relationship between Pulmonary Gas Exchange Function and Brain Uptake Dynamics Investigated with Hyperpolarized 129Xe MR Imaging and Spectroscopy in a Murine Model of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a complex multisystem disease associated with comorbidities outside the lungs. The aim of this study was to measure changes in metrics of pulmonary gas exchange function and brain tissue metabolism in a mouse model of COPD using hyperpolarized 129Xe (HP 129Xe) MRI/MR spectroscopy (MRS) and investigate the relationship between the metrics of lung and brain. METHODS: COPD phenotypes were induced in 15 mice by 6-week administration of cigarette smoke extract (CSE) and lipopolysaccharide (LPS). A separate negative control (NC) group was formed of 6 mice administered with saline for 6 weeks. After these 6-week administrations, the pulmonary gas exchange function parameter fD (%) and the rate constant, α (s-1), which are composed of the cerebral blood flow Fi and the longitudinal relaxation rate 1/T1i in brain tissue, were evaluated by HP 129Xe MRI/MRS. RESULTS: The fD of CSE-LPS mice was significantly lower than that of NC mice, which was in parallel with an increase in bronchial wall thickness. The α in the CSE-LPS mice decreased with the decrease of fD in contrast to the trend in the NC mice. To further elucidate the opposed trend, the contribution of T1i was separately determined by measuring Fi. The T1i in the CSE-LPS mice was found to correlate negatively with fD as opposed to the positive trend in the NC mice. The opposite trend in T1i between CSE-LPS and NC mice suggests hypoxia in the brain, which is induced by the impaired oxygen uptake as indicated by the reduced fD. CONCLUSION: This study demonstrates the feasibility of using HP 129Xe MRI/MRS to study pathological mechanisms of brain dysfunction in comorbidities with COPD.

Quantitative Computed Tomography and Response to Pronation in COVID-19 ARDS.

BACKGROUND: The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO2 clearance and those who did not. METHODS: This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the PaO2 /FIO2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs. RESULTS: One hundred twenty-five subjects were enrolled, of which 116 (93%) were O2 responders and 51 (41%) CO2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99). CONCLUSIONS: Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO2 in mechanically ventilated subjects with COVID-19-related ARDS.

Pulmonary function testing in preoperative high-risk patients.

BACKGROUND: Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. METHODS: A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. RESULTS: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. CONCLUSIONS: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.

Mechanisms and consequences of excess exercise ventilation in fibrosing interstitial lung disease.

The causes and consequences of excess exercise ventilation (EEV) in patients with fibrosing interstitial lung disease (f-ILD) were explored. Twenty-eight adults with f-ILD and 13 controls performed an incremental cardiopulmonary exercise test. EEV was defined as ventilation-carbon dioxide output (⩒E-⩒CO2) slope ≥36 L/L. Patients showed lower pulmonary function and exercise capacity compared to controls. Lower DLCO was related to higher ⩒E-⩒CO2 slope in patients (P<0.05). 13/28 patients (46.4%) showed EEV, reporting higher dyspnea scores (P=0.033). Patients with EEV showed a higher dead space (VD)/tidal volume (VT) ratio while O2 saturation dropped to a greater extent during exercise compared to those without EEV. Higher breathing frequency and VT/inspiratory capacity ratio were observed during exercise in the former group (P<0.05). An exaggerated ventilatory response to exercise in patients with f-ILD is associated with a blunted decrease in the wasted ventilation in the physiological dead space and greater hypoxemia, prompting higher inspiratory constraints and breathlessness.

Intraoperative effects of an alveolar recruitment manoeuvre in patients undergoing laparoscopic colon surgery.

INTRODUCTION: Pulmonary atelectasis is common in patients undergoing laparoscopic abdominal surgery under general anaesthesia, which increases the risk of perioperative respiratory complications. Alveolar recruitment manoeuvres (ARM) are used to open up the lung parenchyma with atelectasis, although the duration of their benefit has not been clearly established. The aim of this study was to determine the effectiveness of an ARM in laparoscopic colon surgery, the duration of response over time, and its haemodynamic impact. METHODS: Twenty-five patients undergoing laparoscopic colon surgery were included. After anaesthetic induction and initiation of surgery with pneumoperitoneum, an ARM was performed, and then optimal PEEP determined. Respiratory mechanics and gas exchange variables, and haemodynamic parameters, were analysed before the manoeuvre and periodically over the following 90 min. RESULTS: Three patients were excluded for surgical reasons. The alveolar arterial oxygen gradient went from 94.3 (62.3-117.8) mmHg before to 60.7 (29.6-91.0) mmHg after the manoeuvre (P < .05). This difference was maintained during the 90 min of the study. Dynamic compliance of the respiratory system went from 31.3 ml/cmH2O (26.1-39.2) before the manoeuvre to 46.1 ml/cmH2O (37.5-53.5) after the manoeuvre (P < .05). This difference was maintained for 60 min. No significant changes were identified in any of the haemodynamic variables studied. CONCLUSION: In patients undergoing laparoscopic colon surgery, performing an intraoperative ARM improves the mechanics of the respiratory system and oxygenation, without associated haemodynamic compromise. The benefit of these manoeuvres lasts for at least one hour.

Efectos intraoperatorios de una maniobra de reclutamiento alveolar en pacientes sometidos a cirugía laparoscópica de colon / Intraoperative effects of an alveolar recruitment manoeuvre in patients undergoing laparoscopic colon surgery

Introducción: Las atelectasias pulmonares son habituales en pacientes sometidos a cirugía abdominal laparoscópica bajo anestesia general, aumentando el riesgo de complicaciones respiratorias perioperatorias. Las maniobras de reclutamiento alveolar (MRA) permiten la reexpansión del parénquima atelectasiado, aunque no está claramente establecida la duración de su beneficio. El objetivo de este estudio fue determinar la efectividad de una MRA en cirugía de colon laparoscópica, la duración de la respuesta en el tiempo y su repercusión hemodinámica. Métodos: Se incluyeron 25 pacientes sometidos a cirugía de colon laparoscópica. Tras la inducción anestésica e inicio de la cirugía con neumoperitoneo, se realizó una MRA y determinación posterior de la PEEP óptima. Se analizaron variables de mecánica respiratoria y de intercambio gaseoso, así como parámetros hemodinámicos, antes de la maniobra y periódicamente durante los 90 min siguientes. Resultados: Tres pacientes fueron excluidos por causas quirúrgicas. El gradiente alveoloarterial de oxígeno pasó de 94,3 (62,3-117,8) mmHg antes a 60,7 (29,6-91,0) mmHg después de la maniobra (p < 0,05). Esta diferencia se mantuvo durante los 90 min del estudio. La compliance dinámica del sistema respiratorio pasó de 31,3 mL/cmH2O (26,1-39,2) antes de la maniobra, a 46,1 mL/cmH2O (37,5-53,5) tras la misma (p < 0,05). Esta diferencia se mantuvo durante 60 min. No se identificaron cambios significativos en ninguna de las variables hemodinámicas estudiadas. Conclusión: En pacientes sometidos a cirugía laparoscópica de colon, la realización de una MRA intraoperatoria mejora la mecánica del sistema respiratorio y la oxigenación, sin apreciarse un compromiso hemodinámico asociado. El beneficio de estas maniobras se extiende al menos durante una hora.(AU)

Introduction: Pulmonary atelectasis is common in patients undergoing laparoscopic abdominal surgery under general anaesthesia, which increases the risk of perioperative respiratory complications. Alveolar recruitment manoeuvres (ARM) are used to open up the lung parenchyma with atelectasis, although the duration of their benefit has not been clearly established. The aim of this study was to determine the effectiveness of an ARM in laparoscopic colon surgery, the duration of response over time, and its haemodynamic impact. Methods: Twenty-five patients undergoing laparoscopic colon surgery were included. After anaesthetic induction and initiation of surgery with pneumoperitoneum, an ARM was performed, and then optimal PEEP determined. Respiratory mechanics and gas exchange variables, and haemodynamic parameters, were analysed before the manoeuvre and periodically over the following 90 minutes. Results: Three patients were excluded for surgical reasons. The alveolar arterial oxygen gradient went from 94.3 (62.3-117.8) mmHg before to 60.7 (29.6-91.0) mmHg after the manoeuvre (P < .05). This difference was maintained during the 90 minutes of the study. Dynamic compliance of the respiratory system went from 31.3 ml/cmH2O (26.1-39.2) before the manoeuvre to 46.1 ml/cmH2O (37.5-53.5) after the manoeuvre (P < .05). This difference was maintained for 60 minutes. No significant changes were identified in any of the haemodynamic variables studied. Conclusion: In patients undergoing laparoscopic colon surgery, performing an intraoperative ARM improves the mechanics of the respiratory system and oxygenation, without associated haemodynamic compromise. The benefit of these manoeuvres lasts for at least one hour.(AU)

No sex differences in oxygen uptake or extraction kinetics in the moderate or heavy exercise intensity domains.

The integrative response to exercise differs between sexes, with oxidative energy contribution purported as a potential mechanism. The present study investigated whether this difference was evident in the kinetics of oxygen uptake (V̇o2) and extraction (HHb + Mb) during exercise. Sixteen adults (8 males, 8 females, age: 27 ± 5 yr) completed three experimental visits. Incremental exercise testing was performed to obtain lactate threshold and V̇o2peak. Subsequent visits involved three 6-min cycling bouts at 80% of lactate threshold and one 30-min bout at a work rate of 30% between the lactate threshold and power at V̇o2peak. Pulmonary gas exchange and near-infrared spectroscopy of the vastus lateralis were used to continuously sample V̇o2 and HHb + Mb, respectively. The phase II V̇o2 kinetics were quantified using monoexponential curves during moderate and heavy exercise. Slow component amplitudes were also quantified for the heavy-intensity domain. Relative V̇o2peak values were not different between sexes (P = 0.111). Males achieved ∼30% greater power outputs (P = 0.002). In the moderate- and heavy-intensity domains, the relative amplitude of the phase II transition was not different between sexes for V̇o2 (∼24 and ∼40% V̇o2peak, P ≥ 0.179) and HHb + Mb (∼20 and ∼32% ischemia, P ≥ 0.193). Similarly, there were no sex differences in the time constants for V̇o2 (∼28 s, P ≥ 0.385) or HHb + Mb (∼10 s, P ≥ 0.274). In the heavy-intensity domain, neither V̇o2 (P ≥ 0.686) or HHb + Mb (P ≥ 0.432) slow component amplitudes were different between sexes. The oxidative response to moderate- and heavy-intensity exercises did not differ between males and females, suggesting similar dynamic responses of oxidative metabolism during intensity-matched exercise.NEW & NOTEWORTHY This study demonstrated no sex differences in the oxidative response to moderate- and heavy-intensity cycling exercise. The change in oxygen uptake and deoxyhemoglobin were modeled with monoexponential curve fitting, which revealed no differences in the rate of oxidative energy provision between sexes. This provides insight into previously reported sex differences in the integrative response to exercise.

Diffusing Capacity as a Predictor of Hospitalizations in a Clinical Cohort of Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) hospitalizations are a major burden on patients. Diffusing capacity of the lung for carbon monoxide (DlCO) is a potential predictor that has not been studied in large cohorts. Objectives: This study used electronic health record data to evaluate whether clinically obtained DlCO predicts COPD hospitalizations. Methods: We performed time-to-event analyses of individuals with COPD and DlCO measurements from the Johns Hopkins COPD Precision Medicine Center of Excellence. Cox proportional hazard methods were used to model time from DlCO measurement to first COPD hospitalization and composite first hospitalization or death, adjusting for age, sex, race, body mass index, smoking status, forced expiratory volume in 1 second (FEV1), history of prior COPD hospitalization, and comorbidities. To identify the utility of including DlCO in risk models, area under the receiver operating curve (AUC) values were calculated for models with and without DlCO. Results were externally validated in a separate analogous cohort. Results: Of 2,793 participants, 368 (13%) had a COPD hospitalization within 3 years. In adjusted analyses, for every 10% decrease in DlCO% predicted, risk of COPD hospitalization increased by 10% (hazard ratio, 1.1; 95% confidence interval, 1.1-1.2; P < 0.001). Similar associations were observed for COPD hospitalizations or death. The model including demographics, comorbidities, FEV1, DlCO, and prior COPD hospitalizations performed well, with an AUC of 0.85 and an AUC of 0.84 in an external validation cohort. Conclusions: Diffusing capacity is a strong predictor of COPD hospitalizations in a clinical cohort of individuals with COPD, independent of airflow obstruction and prior hospitalizations. These findings support incorporation of DlCO in risk assessment of patients with COPD.

Rare Cause of Severe Dyspnea After Tracheotomy-Negative Pressure Pulmonary Edema.

Deep neck infections are serious conditions and can present with acute upper airway obstruction. Our priority in the treatment is to ensure airway safety, and tracheotomy may be needed to overcome the upper airway obstruction. Unceasing dyspnea after tracheotomy should suggest serious pulmonary pathologies in patients with upper airway obstruction due to deep neck infection. Acute/chronic obstruction resolved after tracheotomy or upper respiratory tract surgical procedures of obstructive sleep apnea patients can turn into severe dyspnea with pulmonary edema. In this report, we present a 46-year-old male patient with negative pressure pulmonary edema as a complication of tracheotomy. The tracheotomy was performed due to severe upper airway obstruction secondary to a deep neck infection. The importance of early diagnosis and prompt treatment of this rare entity after unceasing dyspnea despite tracheotomy is discussed in the light of the current literature.

Exercise evaluation with metabolic and ventilatory responses and blood lactate concentration in mice.

This study aimed to clarify the differential exercise capacity between 2-month-old and 10-month-old mice using an incremental running test. Metabolic and ventilatory responses and blood lactate concentration were measured to evaluate exercise capacity. We examined whether incremental running test results reflected metabolic and ventilatory responses and blood lactate concentration observed during the steady-state running test. Metabolic response significantly declined with age, whereas ventilatory response was similar between the groups. A low-intensity/moderate exercise load of 10/min in an incremental running test was performed on both mice for 30 min. They showed a characteristic pattern in ventilatory response in 10-month mice. The results of incremental running tests didn't necessarily reflect the steady-state metabolic and ventilatory responses because some parameters showed an approximation and others did not in incremental and steady-state tests, which changed with age. Our study suggests metabolic and ventilatory responses depending on age and provides basic knowledge regarding the objective and quantitative assessment of treadmill running in an animal model.

Lung Volume Dependence and Repeatability of Hyperpolarized 129Xe MRI Gas Uptake Metrics in Healthy Volunteers and Participants with COPD.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 (129Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated 129Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC). The remaining 17 participants underwent imaging at TLC, RV+FVC/3, and residual volume (RV). Signal ratios between membrane, red blood cell (RBC), and gas-phase compartments were calculated using hierarchical iterative decomposition of water and fat with echo asymmetry and least-squares estimation (ie, IDEAL). Repeatability was assessed using coefficient of variation and intraclass correlation coefficient, and volume relationships were assessed using Spearman correlation and Wilcoxon rank sum tests. Results: Gas uptake metrics were repeatable at RV+FVC/3 (intraclass correlation coefficient = 0.88 for membrane/gas; 0.71 for RBC/gas, and 0.88 for RBC/membrane). Relative ratio changes were highly correlated with relative volume changes for membrane/gas (r = -0.97) and RBC/gas (r = -0.93). Membrane/gas and RBC/gas measured at RV+FVC/3 were significantly lower in the COPD group than the corresponding healthy group (P ≤ .001). However, these differences lessened upon correction for individual volume differences (P = .23 for membrane/gas; P = .09 for RBC/gas). Conclusion: Dissolved-phase 129Xe MRI-derived gas uptake metrics were repeatable but highly dependent on lung volume during measurement.Keywords: Blood-Air Barrier, MRI, Chronic Obstructive Pulmonary Disease, Pulmonary Gas Exchange, Xenon Supplemental material is available for this article © RSNA, 2023.

A Meta-Analysis of Remote Ischemic Preconditioning in Lung Surgery and Its Potential Role in COVID-19.

Purpose: To determine the effects of remote ischemic preconditioning (RIPC) on pulmonary gas exchange in people undergoing pulmonary surgery and discuss a potential role of RIPC in COVID-19. Method: A search for studies examining the effects of RIPC after pulmonary surgery was performed. RevMan was used for statistical analyses examining measures of A-ado2, Pao2/Fio2, respiratory index (RI), a/A ratio and Paco2 obtained earlier after surgery (i.e., 6-8 hours) and later after surgery (i.e., 18-24 hours). Results: Four trials were included (N = 369 participants). Significant (p < 0.05) overall effects of RIPC were observed early after surgery on A-ado2 and RI (SMD -0.84 and SMD -1.23, respectively), and later after surgery on RI, Pao2/Fio2, and a/A ratio (SMD -0.39, 0.72, and 1.15, respectively) with the A-ado2 approaching significance (p = 0.05; SMD -0.45). Significant improvements in inflammatory markers and oxidative stress after RIPC were also observed. Conclusions: RIPC has the potential to improve pulmonary gas exchange, inflammatory markers, and oxidative stress in people with lung disease undergoing lung surgery and receiving mechanical ventilation. These potential improvements may be beneficial for people with COVID-19, but further investigation is warranted.

Objectif : déterminer les effets du préconditionnement ischémique à distance (PCID) sur les échanges gazeux pulmonaires chez les personnes qui subissent une opération pulmonaire et discuter du rôle potentiel du PCID sur la COVID-19. Méthodologie : les chercheurs ont procédé à une recherche sur les effets du PCID après une opération pulmonaire. Ils ont utilisé le logiciel RevMan pour effectuer les analyses statistiques des mesures du gradient artério-alvéolaire (A-ao2), du rapport entre la pression partielle d'oxygène et la fraction inspirée en oxygène (Pao2/Fio2), de l'indice respiratoire (IR), du gradient alvéolo-artériel (a-A) et de la pression partielle de dioxyde de carbone (Paco2) obtenus de six à huit heures après l'opération, puis de 18 à 24 heures après l'opération. Résultats : les chercheurs ont inclus quatre études (N = 369 participants). Ils ont observé des effets globaux importants (p < 0,05) du PCID peu après l'opération sur l'A-ao2 et l'IR (DMS = −0,84 et DMS = −1,23, respectivement), puis plus tard après l'opération sur l'IR, le Pao2/Fio2 et le gradient a-A (DMS = −0,39, 0,72 et 1,15, respectivement), et l'A-ao2 avoisine une valeur significative (p = 0,05; DMS = −0,45). Ils ont également observé des améliorations notables aux marqueurs inflammatoires et au stress oxydatif après le PCID. Conclusions : le PCID a le potentiel d'améliorer les échanges gazeux pulmonaires, les marqueurs inflammatoires et le stress oxydatif chez les personnes atteintes d'une maladie pulmonaire qui subissent une opération pulmonaire et reçoivent une ventilation mécanique. Ces améliorations potentielles peuvent être bénéfiques aux personnes atteintes de la COVID-19, mais d'autres recherches s'imposent.

Hyperoxia-induced stepwise reduction in blood flow through intrapulmonary, but not intracardiac, shunt during exercise.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) (QIPAVA) increases during exercise breathing air, but it has been proposed that QIPAVA is reduced during exercise while breathing a fraction of inspired oxygen ([Formula: see text]) of 1.00. It has been argued that the reduction in saline contrast bubbles through IPAVA is due to altered in vivo microbubble dynamics with hyperoxia reducing bubble stability, rather than closure of IPAVA. To definitively determine whether breathing hyperoxia decreases saline contrast bubble stability in vivo, the present study included individuals with and without patent foramen ovale (PFO) to determine if hyperoxia also eliminates left heart contrast in people with an intracardiac right-to-left shunt. Thirty-two participants consisted of 16 without a PFO; 8 females, 8 with a PFO; 4 females, and 8 with late-appearing left-sided contrast (4 females) completed five, 4-min bouts of constant-load cycle ergometer exercise (males: 250 W, females: 175 W), breathing an [Formula: see text] = 0.21, 0.40, 0.60, 0.80, and 1.00 in a balanced Latin Squares design. QIPAVA was assessed at rest and 3 min into each exercise bout via transthoracic saline contrast echocardiography and our previously used bubble scoring system. Bubble scores at [Formula: see text]= 0.21, 0.40, and 0.60 were unchanged and significantly greater than at [Formula: see text]= 0.80 and 1.00 in those without a PFO. Participants with a PFO had greater bubble scores at [Formula: see text]= 1.00 than those without a PFO. These data suggest that hyperoxia-induced decreases in QIPAVA during exercise occur when [Formula: see text] ≥ 0.80 and is not a result of altered in vivo microbubble dynamics supporting the idea that hyperoxia closes QIPAVA.

Perfil de pacientes evaluados con el Test de Capacidad de Difusión de Monóxido de Carbono: Una experiencia chilena

Antecedentes: La prueba de capacidad de difusión de monóxido de carbono (DLCO) es una evaluación de función pulmonar rutinaria y no invasiva clínicamente útil para determinar el estado de la función pulmonar en pacientes con trastornos crónicos como la enfermedad pulmonar intersticial difusa (EPID). Objetivo: Describir el perfil sociodemográfico y clínico de usuarios de la prueba DLCO en Valdivia, Chile. Materiales y Métodos: Estudio observacional, retrospectivo, de base documental. A partir de registros de 490 pacientes que se realizaron la prueba DLCO entre 2017 y 2019, se describen características sociodemográficas, clínicas y reporte de consumo de cigarrillo como cigarrillos/d e índice paquetes/año (IPA), comparando por sexo. Resultados: La mayor proporción de evaluados fueron mujeres (61%), con una edad mediana de 65 años, mayor en mujeres (66 vs 64 años; p = 0,0361). La mayoría consultaron por EPID (54,5%). Según estado nutricional, 38% presentó preobesidad y 24,7% obesidad I (24,7%), destacando que 40,5% de las mujeres y 33% de los hombres se encontraron en alguna categoría de obesidad. Entre quienes reportaron información de consumo de cigarrillos (n = 346, 70,6%), 14,7% (n = 51) eran consumidores actuales, con un consumo mediano de 10 cigarrillos/d, sin diferencias por sexo. Entre exfumadores (n = 144; 50% hombres/mujeres) hubo significativamente menor consumo diario (5 vs 15; p = 0,0300) y de IPA (7 vs 18; p = 0,0083) en mujeres. Conclusiones: En usuarios de DLCO el principal diagnóstico de consulta fue EPID. Destacó alta frecuencia de obesidad y tabaquismo, sin diferencia de consumo por sexo en fumadores actuales, pero sí en exfumadores.

Background: The carbon monoxide diffusion capacity test (DLCO) is a clinically useful, routine, non-invasive lung function assessment to determine the status of lung function in patients with chronic disorders such as interstitial lung disease (ILD). Aim: To describe the sociodemographic and clinical profile of users of the DLCO test in Valdivia, Chile. Materials and Methods: Observational, retrospective, documentary-based study. From the records of 490 patients who underwent the DLCO test between 2017 and 2019, sociodemographic and clinical characteristics and reports of cigarette consumption are described, such as cigarettes/d and pack-year index (PYI), comparing by sex. Results: The highest proportion of those evaluated were women (61%), with a median age of 65 years, higher in women (66 vs. 64 years; p = 0.0361). The majority consulted for ILD (54.5%). According to nutritional status, 38% presented pre-obesity and 24.7% obesity I (24.7%), highlighting that 40.5% of women and 33% of men were in some category of obesity. Among those who reported information on cigarette consumption (n = 346, 70.6%), 14.7% (n = 51) were current consumers, with a median consumption of 10 cigarettes/d, without differences by sex. Among exsmokers (n = 144; 50% men/women) there was significantly less daily (5 vs 15; p = 0.0300) and IPA (7 vs 18; p = 0.0083) consumption in women. Conclusions: In DLCO users, the main consultation diagnosis was ILD. High frequency of obesity and smoking stood out, with no difference in consumption by sex in current smokers, but yes in ex-smokers.

Hemorrhagic Shock: Blood Marker Sequencing and Pulmonary Gas Exchange.

BACKGROUND: The early identification of internal hemorrhage in critically ill patients may be difficult. Besides circulatory parameters, hemoglobin and lactate concentration, metabolic acidosis and hyperglycemia serve as laboratory markers for bleeding. In this experiment, we examined pulmonary gas exchange in a porcine model of hemorrhagic shock. Moreover, we sought to investigate if a chronological order of appearance regarding hemoglobin, lactatemia, standard base excess/deficit (SBED) and hyperglycemia exists in early severe hemorrhage. METHODS: In this prospective, laboratory study, twelve anesthetized pigs were randomly allocated to exsanguination or a control group. Animals in the exsanguination group (n = 6) endured a 65% blood loss over 20 min. No intravenous fluids were administered. Measurements were taken before, immediately after, and at 60 min after the completed exsanguination. Measurements included pulmonary and systemic hemodynamic variables, hemoglobin concentration, lactate, base excess (SBED), glucose concentration, arterial blood gases, and a multiple inert gas assessment of pulmonary function. RESULTS: At baseline, variables were comparable. Immediately after exsanguination, lactate and blood glucose were increased (p = 0.001). The arterial partial pressure of oxygen was increased at 60 min after exsanguination (p = 0.04) owing to a decrease in intrapulmonary right-to-left shunt and less ventilation-perfusion inequality. SBED was different to the control only at 60 min post bleeding (p < 0.001). Hemoglobin concentration did not change at any time (p = 0.97 and p = 0.14). CONCLUSIONS: In experimental shock, markers of blood loss became positive in chronological order: lactate and blood glucose concentrations were raised immediately after blood loss, while changes in SBED lagged behind and became significant one hour later. Pulmonary gas exchange is improved in shock.

Unstable SpO2 in preterm infants: The key role of reduced ventilation to perfusion ratio.

Introduction: Instability of peripheral oxyhemoglobin saturation (SpO2) in preterm infants is correlated with late disability and is poorly understood. We hypothesised that a reduced ventilation to perfusion ratio (VA/Q) is the key predisposing factor for SpO2 instability. Methods: We first used a mathematical model to compare the effects of reduced VA/Q or shunt on SaO2 stability (SaO2 and SpO2 are used for model and clinical studies respectively). Stability was inferred from the slope of the SaO2 vs. inspired oxygen pressure (P IO2) curve as it intersects the 21 kPa P IO2 line (breathing air). Then, in a tertiary neonatal intensive care unit, paired hourly readings of SpO2 and P IO2 were recorded over a 24 h period in week old extremely preterm infants. We noted SpO2 variability and used an algorithm to derive VA/Q and shunt from the paired SpO2 and P IO2 measurements. Results: Our model predicted that when VA/Q < 0.4, a 1% change in P IO2 results in >8% fluctuation in SaO2 at 21 kPa P IO2. In contrast, when a 20% intrapulmonary shunt was included in the model, a 1% change in P IO2 results in <1% fluctuation in the SaO2. Moreover, further reducing the VA/Q from 0.4 to 0.3 at 21 kPa P IO2 resulted in a 24% fall in SaO2. All 31 preterm infants [mean gestation (±standard deviation) 26.2 (±1) week] had VA/Q < 0.74 (normal >0.85) but only two infants had increased shunt at 1.1 (±0.5) weeks' postnatal age. Median (IQR) SpO2 fluctuation was 8 (7)%. The greatest SpO2 fluctuations were seen in infants with VA/Q < 0.52 (n = 10): SpO2 fluctuations ranged from 11%-17% at a constant P IO2 when VA/Q < 0.52. Two infants had reduced VA/Q and increased shunt (21% and 27%) which resolved into low VA/Q after 3-6 h. Discussion: Routine monitoring of P IO2 and SpO2 can be used to derive a hitherto elusive measure of VA/Q. Predisposition to SpO2 instability results from reduced VA/Q rather than increased intrapulmonary shunt in preterm infants with cardiorespiratory disease. SpO2 instability can be prevented by a small increase in P IO2.

Pulmonary diffusing capacity to nitric oxide and carbon monoxide during exercise and in the supine position: a test-retest reliability study.

NEW FINDINGS: What is the central question in this study? How reliable is the combined measurement of the pulmonary diffusing capacity to carbon monoxide and nitric oxide (DLCO/NO ) during exercise and in the resting supine position, respectively? What is the main finding and its importance? The DLCO/NO technique is reliable with a very low day-to-day variability both during exercise and in the resting supine position, and may thus provide a useful physiological outcome that reflects the alveolar-capillary reserve in humans. ABSTRACT: DLCO/NO , the combined single-breath measurement of the diffusing capacity to carbon monoxide (DLCO ) and nitric oxide (DLNO ) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar-capillary reserve. In the present study, we investigated the between-day test-retest reliability of DLCO/NO -based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test-retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar-capillary reserve, both during exercise and in the supine position.

Responses to exercise in systemic sclerosis-associated interstitial lung disease.

INTRODUCTION: Pulmonary complications in systemic sclerosis (SSc) significantly increase morbidity and mortality. Our aim was to determine the factors limiting exercise capacity in SSc patients with and without interstitial lung disease (ILD), and to identify and quantify abnormalities during exercise that might assist in clinical assessment of this complication. METHODS: Fifteen patients with SSc and ILD (SSc-ILD) were compared with 10 patients with SSc without ILD and 9 age- and sex-matched normal volunteers. Subjects performed symptom-limited incremental treadmill exercise with online measurement of respiratory gas exchange, arterial blood gas sampling and measurement of neurohormones in venous blood. RESULTS: Patients with SSc-ILD had lower exercise capacity than SSc patients without ILD or normal subjects (peak oxygen consumption (PV̇O2 ) (17.1 [4.2] vs. 22.0 [4.7] and 23.0 [5.4] ml kg-1 min-1 , respectively, mean [SD], p < 0.01 ANOVA), but PV̇O2 did not correlate with static pulmonary function measurements. Ventilatory equivalent for CO2 (V̇E/V̇CO2 ; nadir) was higher in SSc-ILD patients than the other two groups (36.6 [8.0] vs. 29.9 [4.4] and 30.0 [2.5], p < 0.005) as were peak exercise dead-space tidal volume ratio (0.44 [0.06] vs. 0.26 [0.09] and 0.26 [0.05], p < 0.001) and peak exercise alveolar-arterial difference (28.9 [16.9] vs. 18.8 [14.0] and 11.5 [6.9] mmHg, p < 0.05). Atrial natriuretic peptide was elevated in both SSc patient groups. CONCLUSIONS: SSc-ILD results in lower exercise capacity than SSc without ILD, and abnormalities of gas exchange are seen. The possible use of cardiopulmonary exercise testing to identify disease and quantify impairment in SSc-ILD merits further study.

Diffusing Capacity and Mortality in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) mortality risk is often estimated using the BODE (body mass index, obstruction, dyspnea, exercise capacity) index, including body mass index, forced expiratory volume in 1 second, dyspnea score, and 6-minute walk distance. Diffusing capacity of the lung for carbon monoxide (DlCO) is a potential predictor of mortality that reflects physiology distinct from that in the BODE index. Objectives: This study evaluated DlCO as a predictor of mortality using participants from the COPDGene study. Methods: We performed time-to-event analyses of individuals with COPD (former or current smokers with forced expiratory volume in 1 second/forced vital capacity < 0.7) and DlCO measurements from the COPDGene phase 2 visit. Cox proportional hazard methods were used to model survival, adjusting for age, sex, pack-years, smoking status, BODE index, computed tomography (CT) percent emphysema (low attenuation areas below -950 Hounsfield units), CT airway wall thickness, and history of cardiovascular or kidney diseases. C statistics for models with DlCO and BODE scores were used to compare discriminative accuracy. Results: Of 2,329 participants, 393 (16.8%) died during the follow-up period (median = 4.9 yr). In adjusted analyses, for every 10% decrease in DlCO percent predicted, mortality increased by 28% (hazard ratio = 1.28; 95% confidence interval, 1.17-1.41, P < 0.001). When compared with other clinical predictors, DlCO percent predicted performed similarly to BODE (C statistic DlCO = 0.68; BODE = 0.70), and the addition of DlCO to BODE improved its discriminative accuracy (C statistic = 0.71). Conclusions: Diffusing capacity, a measure of gas transfer, strongly predicted all-cause mortality in individuals with COPD, independent of BODE index and CT evidence of emphysema and airway wall thickness. These findings support inclusion of DlCO in prognostic models for COPD.