Alveolar Gas Research Articles

Impact of high-flow nasal oxygen therapy on postoperative atelectasis and reintubation rate after paediatric cardiac surgery.

Airway problems emerging after congenital cardiac surgery operations may have an impact on mortality and morbidity. Recently, to improve alveolar gas exchange and reduce respiratory effort, high-flow nasal cannula (HFNC) has started to be used in paediatric cases. This study aimed to evaluate the potential effects of high-flow nasal oxygen therapy on postoperative atelectasis development and reintubation rate in paediatric cardiac surgery patients. This study was conducted retrospectively in term newborns and infants younger than six months of age who underwent congenital cardiac surgery operation from 1 November 2022 to 1 November 2023 and were followed in the paediatric cardiac ICU. Patients who were receiving mechanical ventilator support at least 12 hours postoperatively were evaluated for the development of postoperative atelectasis and reintubation in the first 3 days of extubation. The patients were grouped as HFNC and non-HFNC users. Demographic characteristics, surgery type, and ICU clinical follow-up data were obtained from medical records. The results were statistically evaluated. A total of 40 patients who did not use HFNC in the early postoperative period and 40 patients with HFNC in the late period during the study period were included in the study. The median age was 1 month (IQR 15 days-2 months) with equal gender distribution. Among patients, 70% of them were in the neonatal age group. Reintubation rates in the first 72 hours in HFNC users and non-HFNC users were 2.5% and 12.5%, respectively (p < 0.05). The median postoperative atelectasis scores at 24, 48, and 72 hours of extubation were 2 versus 2.5 (p > 0.05), 1.5 versus 3.5 (p < 0.05), and 1 versus 3 (p < 0.05) in HFNC users and non-HFNC users, respectively. HFNC therapy may have a positive effect on preventing atelectasis and reducing the reintubation rate in the early postoperative period.

Impaired Myofibroblast Proliferation is a Central Feature of Pathologic Post-Natal Alveolar Simplification.

Premature infants with bronchopulmonary dysplasia (BPD) have impaired alveolar gas exchange due to alveolar simplification and dysmorphic pulmonary vasculature. Advances in clinical care have improved survival for infants with BPD, but the overall incidence of BPD remains unchanged because we lack specific therapies to prevent this disease. Recent work has suggested a role for increased transforming growth factor-beta (TGFβ) signaling and myofibroblast populations in BPD pathogenesis, but the functional significance of each remains unclear. Here, we utilize multiple murine models of alveolar simplification and comparative single-cell RNA sequencing to identify shared mechanisms that could contribute to BPD pathogenesis. Single-cell RNA sequencing reveals a profound loss of myofibroblasts in two models of BPD and identifies gene expression signatures of increased TGFβ signaling, cell cycle arrest, and impaired proliferation in myofibroblasts. Using pharmacologic and genetic approaches, we find no evidence that increased TGFβ signaling in the lung mesenchyme contributes to alveolar simplification. In contrast, this is likely a failed compensatory response, since none of our approaches to inhibit TGFb signaling protect mice from alveolar simplification due to hyperoxia while several make simplification worse. In contrast, we find that impaired myofibroblast proliferation is a central feature in several murine models of BPD, and we show that inhibiting myofibroblast proliferation is sufficient to cause pathologic alveolar simplification. Our results underscore the importance of impaired myofibroblast proliferation as a central feature of alveolar simplification and suggest that efforts to reverse this process could have therapeutic value in BPD.

Multi-compartment V/Q lung modeling: Log normal distributions of inspired or expired alveolar gas?

Using a 50-compartment Python-coded mathematical lung model, we compared mixed venous blood flow (Q) distributions and arterial oxygen tension/inspired oxygen fraction (PaO2/FiO2) relationships in lungs modeled with log normal distributions (LND) of inspired (VI) versus expired (VA) alveolar gas volumes. In lungs with normal V/Q heterogeneity, Q versus VA/Q and Q versus VI/Q distributions were similar with either approach, and PaO2/FiO2 sequences remained indistinguishable. In V/Q heterogeneous lungs at high FiO2, VILND generated low Q versus VA/Q shoulders and some negative VA units, while VALND preserved Q versus VA/Q log normality by blood flow diversion from low VI/Q units. We managed VILND-induced negative VA units either by shunt conversion (VI decreased to 0) or VI redistribution simulating collateral ventilation (VI increased till VA = 0). Comparing oxygen transfer: VALND > VILND (redistribution) > VILND (shunt). In V/Q heterogeneous lungs VALND and VILND (redistribution) regained near optimal oxygen transfer on 100% oxygen, while impairment persisted with VILND (shunt). Unlike VALND, VILND (redistribution) produced Q versus VA/Q distributions in V/Q heterogeneity compatible with multiple inert gas (MIGET) reports. VILND (redistribution) is a physiologically-based MIGET-compatible alternative to West's original VALND lung modeling approach.

Methylprednisolone alleviates lung injury in sepsis by regulating miR-151-5p/USP38 pathway

BackgroundAcute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP) is commonly used as a treatment for ALI to reduce inflammation, yet its molecular mechanism remains unclear. This study aims to explore the underlying mechanisms of MP on ALI in a model induced by lipopolysaccharide (LPS). Material and MethodsThe proliferation, viability, apoptosis, and miR-151-5p expression of alveolar type II epithelial cells (AECII) were detected using the cell EdU assay, Annexin V/PI Apoptosis Kit, counting kit-8 (CCK-8) assay, and RT-qPCR. Western blot analysis was used to detect the Usp38 protein level. IL-6 and TNF-α were measured by ELISA. The combination of miR-151-5p and USP38 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay. ResultsMP greatly improved pulmonary function in vivo, reduced inflammation, and promoted the proliferation of the alveolar type II epithelial cells (AECII) in vitro. By comparing the alterations of microRNAs in lung tissues between MP treatment and control groups, we found that miR-151-5p exhibited a significant increase after LPS-treated AECII, but decreased after MP treatment. Confirmed by a luciferase reporter assay, USP38, identified as a downstream target of miR-151-5p, was found to increase after MP administration. Inhibition of miR-151-5p or overexpression of USP38 in AECII significantly improved the anti-inflammatory, anti-apoptotic, and proliferation-promotive effects of MP. ConclusionIn summary, our data demonstrated that MP alleviates the inflammation and apoptosis of AECII induced by LPS, and promotes the proliferation of AECII partially via miR-151-5p suppression and subsequent USP38 activation.

Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200μmol/kg, IV), worsens the adverse actions of fentanyl (75μg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.

Lung Diseases and Rare Disorders: Is It a Lysosomal Storage Disease? Differential Diagnosis, Pathogenetic Mechanisms and Management.

Pulmonologists may be involved in managing pulmonary diseases in children with complex clinical pictures without a diagnosis. Moreover, they are routinely involved in the multidisciplinary care of children with rare diseases, at baseline and during follow-up, for lung function monitoring. Lysosomal storage diseases (LSDs) are a group of genetic diseases characterised by a specific lysosomal enzyme deficiency. Despite varying pathogen and organ involvement, they are linked by the pathological accumulation of exceeding substrates, leading to cellular toxicity and subsequent organ damage. Less severe forms of LSDs can manifest during childhood or later in life, sometimes being underdiagnosed. Respiratory impairment may stem from different pathogenetic mechanisms, depending on substrate storage in bones, with skeletal deformity and restrictive pattern, in bronchi, with obstructive pattern, in lung interstitium, with altered alveolar gas exchange, and in muscles, with hypotonia. This narrative review aims to outline different pulmonary clinical findings and a diagnostic approach based on key elements for differential diagnosis in some treatable LSDs like Gaucher disease, Acid Sphingomyelinase deficiency, Pompe disease and Mucopolysaccharidosis. Alongside their respiratory clinical aspects, which might overlap, we will describe radiological findings, lung functional patterns and associated symptoms to guide pediatric pulmonologists in differential diagnosis. The second part of the paper will address follow-up and management specifics. Recent evidence suggests that new therapeutic strategies play a substantial role in preventing lung involvement in early-treated patients and enhancing lung function and radiological signs in others. Timely diagnosis, driven by clinical suspicion and diagnostic workup, can help in treating LSDs effectively.

Analyzing the performance of a bio-sensor integrated improved blended learning model for accurate pneumonia prediction

Pneumonia has been considered a life-threatening disease for elderly human beings and those with weakened immune systems in the present medical era. The contemporary scenario highlights the significance of intelligent and automatic handheld devices to detect pneumonia and other pulmonary diseases. Hence, this research has designed an improved blended learning paradigm (IBLP) for real-time pneumonia detection from chest X-rays, and early detection of lung diseases from alveolar gas using biosensors with a graphical processing unit (GPU) developed to overcome and resolve such challenges. It emphasizes the medical applications of blended learning techniques, particularly for identifying pneumonia from chest X-ray images and other pulmonary diseases from exhaled breath using biosensors and support vector machine (SVM). The experimental findings indicate that the blended learning based VGG16 (91.99%) consistently outperforms the VGG19 (88.91%) and ResNet50 (87.02%) model in diagnostic accuracy. IBLP VGG16 provided 95.5% precision, 97.69% F1 score, and a 100% recall rate with no false-negative results. The future of X-ray classification in pneumonia diagnosis will likely involve using artificial intelligence-based systems that can provide accurate and timely analysis of X-ray images, thereby improving patient outcomes and reducing healthcare costs.

Rhodomyrtus tomentosa (Aiton) Hassk. (haramonting) protects against allethrin-exposed pulmo damage in rats: mechanistic interleukins.

Inhaling Allethrin (C19H26O3) may induce oxidative stress in lung cells by causing the formation of free radi-cals. Interleukins (IL) are a group of secreted cytokines or proteins and signaling molecules initially produced as an immune response by leukocytes. Rhodomyrtus tomentosa (Aiton) Hassk. (haramonting) contains antioxidants that may prevent lung damage induced by allethrin-containing electric mosquito repellents. In this study, six groups of rats were exposed to allethrin via an electric mosquito repellent, including positive, negative, and comparison control groups and three groups were administered Rhodomyrtus tomentosa (Aiton) Hassk at 100mg/kg BW, 200mg/kg BW, and 300mg/kg BW. After 30days, the pulmonary tissue and the blood were taken for immunohisto-chemical and ELISA analysis. The accumulation of inflammatory cells causes the thickening of the alveolar wall structures. Injuries were more prevalent in the A+ group than in the other groups. The connection between the alveoli and blood capillaries, which can interfere with alveolar gas exchange, is not regulated, and the lu-minal morphology is aberrant, causing damage to the alveolar epithelial cells. Exposure to electric mosquito coils containing allethrin can increase the expression of interleukin-1, interleukin-8, interleukin-9, and interleu-kin-18 in blood serum and tissues while decreasing the expression of interleukin-6 and interleukin-10. Like the Vitamin C group, Rhodomyrtus tomentosa can increase alveolar histological alterations by decreasing the ex-pression of IL-1β, IL-8, IL-9, and IL-18 while increasing IL-6 and IL-10. So that this plant can be developed in the future as a drug to prevent lung harm from exposure.

Resolving the Complexity: A Comprehensive Review on Carbon Monoxide Diffusion Capacity in Chronic Obstructive Pulmonary Disease Patients.

This review comprehensively examines the intricate relationship between carbon monoxide (CO) diffusion capacity and chronic obstructive pulmonary disease (COPD). COPD, comprising chronic bronchitis and emphysema, presents a substantial global health burden, necessitating a nuanced understanding of pulmonary function parameters for effective diagnosis and management. The review delves into the physiological underpinnings, measurement techniques, and factors influencing CO diffusion capacity, emphasizing its pivotal role in assessing alveolar gas exchange efficiency. Key findings elucidate correlations between altered diffusion capacity and the severity of COPD, providing clinicians with valuable insights into disease progression. Considerations of age, gender, and ethnic disparities in normal CO diffusion capacity values highlight the importance of personalized interpretations. The clinical implications extend beyond diagnosis, influencing COPD management and prognostication, with potential applications in predicting treatment response. The review outlines avenues for future research, including advancements in measurement technologies and the exploration of novel imaging modalities and biomarkers. Ultimately, this review serves as a foundation for refining diagnostic approaches and treatment strategies and enhancing patient care in the dynamic landscape of COPD.

TGF-βR2 signaling coordinates pulmonary vascular repair after viral injury in mice and human tissue.

Disruption of pulmonary vascular homeostasis is a central feature of viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants of the outcome of severe lung injury. A more granular understanding of the fundamental mechanisms driving reconstitution of lung endothelium is necessary to facilitate therapeutic vascular repair. Here, we demonstrated that TGF-β signaling through TGF-βR2 (transforming growth factor-β receptor 2) is activated in pulmonary ECs upon influenza infection, and mice deficient in endothelial Tgfbr2 exhibited prolonged injury and diminished vascular repair. Loss of endothelial Tgfbr2 prevented autocrine Vegfa (vascular endothelial growth factor α) expression, reduced endothelial proliferation, and impaired renewal of aerocytes thought to be critical for alveolar gas exchange. Angiogenic responses through TGF-βR2 were attributable to leucine-rich α-2-glycoprotein 1, a proangiogenic factor that counterbalances canonical angiostatic TGF-β signaling. Further, we developed a lipid nanoparticle that targets the pulmonary endothelium, Lung-LNP (LuLNP). Delivery of Vegfa mRNA, a critical TGF-βR2 downstream effector, by LuLNPs improved the impaired regeneration phenotype of EC Tgfbr2 deficiency during influenza injury. These studies defined a role for TGF-βR2 in lung endothelial repair and demonstrated efficacy of an efficient and safe endothelial-targeted LNP capable of delivering therapeutic mRNA cargo for vascular repair in influenza infection.

Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration

Lung epithelial regeneration after acute injury requires coordination cellular coordination to pattern the morphologically complex alveolar gas exchange surface. During adult lung regeneration, Wnt-responsive alveolar epithelial progenitor (AEP) cells, a subset of alveolar type 2 (AT2) cells, proliferate and transition to alveolar type 1 (AT1) cells. Here, we report a refined primary murine alveolar organoid, which recapitulates critical aspects of in vivo regeneration. Paired scRNAseq and scATACseq followed by transcriptional regulatory network (TRN) analysis identified two AT1 transition states driven by distinct regulatory networks controlled in part by differential activity of Nkx2-1. Genetic ablation of Nkx2-1 in AEP-derived organoids was sufficient to cause transition to a proliferative stressed Krt8+ state, and AEP-specific deletion of Nkx2-1 in adult mice led to rapid loss of progenitor state and uncontrolled growth of Krt8+ cells. Together, these data implicate dynamic epigenetic maintenance via Nkx2-1 as central to the control of facultative progenitor activity in AEPs.

Abstract 17947: Mathematical Model of Cheyne-Stokes Respirations as an Educational Tool for Understanding Cardiorespiratory Interactions in Heart Failure

Background: Patients with heart failure often develop Cheyne-Stokes Respirations (CSR): a breathing pattern characterized by alternating periods of hyperventilation and apnea. The cardio-respiratory interactions that result in CSR are complex and often difficult to understand for students learning cardiovascular physiology. Aims: We developed a mathematical model of CSR where cardiac output (CO), respiratory rate (RR) and arterial CO 2 (pCO 2 ) can be manipulated to evaluate how periodic fluctuations in different physiological variables develop, thus providing a deeper understanding of cardiorespiratory interactions in heart failure. Methods: Our model consisted of 3 coupled differential equations. (1) pCO 2 is directly proportional to metabolic CO 2 production and inversely proportional to alveolar ventilation (V A ). V A depends on RR, alveolar volume, and CO, with the interaction between CO and ventilation calculated by combining Fick’s principle and the Alveolar Gas Equation. (2) Changes in RR are modeled as a Hill function dependent on pCO 2 . (3) Finally, CO depends on pCO 2 , arterial O 2, and RR. The model was propagated forward in time using Euler’s method. A graphical user interface allows users to easily manipulate variables and observe heart lung interactions. Results: Initial values for RR, CO, and PCO 2 resulting in stable, aperiodic breathing were 10 breaths/min, 6 L/Min, and 40 mmHg, respectively. Perturbing any of these values resulted in periodic fluctuations in RR, CO, and pCO 2 (Figure 1). A key insight of the model is that progressive decreases in CO induce more prominent oscillations in RR and pCO 2 and that pCO 2 directly influences CO. Conclusions: Our mathematical model of cardio-respiratory interactions allows users to easily manipulate physiological variables to graphically visualize how changes in CO and respiratory function give rise to CSR. This may enable students to obtain a deeper understanding of cardiovascular physiology.

Noninvasive Assessment of Impaired Gas Exchange with the Alveolar Gas Monitor Predicts Clinical Deterioration in COVID-19 Patients.

The COVID-19 pandemic magnified the importance of gas exchange abnormalities in early respiratory failure. Pulse oximetry (SpO2) has not been universally effective for clinical decision-making, possibly because of limitations. The alveolar gas monitor (AGM100) adds exhaled gas tensions to SpO2 to calculate the oxygen deficit (OD). The OD parallels the alveolar-to-arterial oxygen difference (AaDO2) in outpatients with cardiopulmonary disease. We hypothesized that the OD would discriminate between COVID-19 patients who require hospital admission and those who are discharged home, as well as predict need for supplemental oxygen during the index hospitalization. Patients presenting with dyspnea and COVID-19 were enrolled with informed consent and had OD measured using the AGM100. The OD was then compared between admitted and discharged patients and between patients who required supplemental oxygen and those who did not. The OD was also compared to SpO2 for each of these outcomes using receiver operating characteristic (ROC) curves. Thirty patients were COVID-19 positive and had complete AGM100 data. The mean OD was significantly (p = 0.025) higher among those admitted 50.0 ± 20.6 (mean ± SD) vs. discharged 27.0 ± 14.3 (mean ± SD). The OD was also significantly (p < 0.0001) higher among those requiring supplemental oxygen 60.1 ± 12.9 (mean ± SD) vs. those remaining on room air 25.2 ± 11.9 (mean ± SD). ROC curves for the OD demonstrated very good and excellent sensitivity for predicting hospital admission and supplemental oxygen administration, respectively. The OD performed better than an SpO2 threshold of <94%. The AGM100 is a novel, noninvasive way of measuring impaired gas exchange for clinically important endpoints in COVID-19.

Lung Volume Reduction Surgery (Clinical Cases)

Emphysema is a chronic lung disease in which the walls of the alveoli in the lungs weaken and collapse; leaving abnormally large residual spaces filled with air even when the patient exhales. The most common symptoms of emphysema are shortness of breath (dyspnea); cough; fatigue; and weight loss. Emphysema often coexists with chronic obstructive pulmonary disease. The treatment of emphysema requires a multidisciplinary approach; including education; exercise; tobacco cessation; oral and inhaled medications; oxygen therapy; and lung transplantation. Lung volume reduction surgery (LVRS) may be an option for patients who experience shortness of breath and whose pulmonary function tests show severe obstruction and enlarged lungs. The surgery aims to remove the least functional part of the lung to improve airflow; diaphragm; and chest wall mechanics; as well as alveolar gas exchange in the remaining lung. Objective — to familiarize doctors with the clinic’s experience in reducing lung volume in patients with bullous emphysema. Materials and methods. Our clinic performed the following surgical interventions to reduce lung volume: VATS resection of large (giant) lung bullae — 14 (77.7 %) cases; VATS lo­­bec­tomy — 2 (11.1 %); lobectomy through thoracotomy — 1 (5.6 %); VATS sublobar resection — 1 (5.6 %). Results and discussion. There were no fatalities. The following postoperative complications were recorded: prolonged under-expansion of the operated lung in 5 (27.7 %) cases; empyema of the residual pleural cavity with bronchial fistula in 1 (5.6 %). The overall incidence of postoperative complications was 33.3 %. Two patients with prolonged underdistension of the operated lung required reoperation (VATS revision of the pleural cavity and redilation). The patient who developed pleural empyema with a bronchial fistula underwent bronchial blockage with a satisfactory result. In all cases of LVRS; a positive clinical effect was recorded in the first 3 months after surgery. During the follow-up period of up to 2 years; only 2 (11.1 %) patients showed no clinical effect and signs of progression of chronic obstructive pulmonary disease and respiratory failure were observed. Conclusions. Lung volume reduction surgery is a method of treating bullous lung disease that allows achieving overall treatment effectiveness in the follow-up period of up to 3 months in 100 % of cases; and in the follow-up period of up to 2 years — in 89.9 %. The high rate of postoperative complications in LVRS requires a physician to carefully select patients for surgery and monitor their condition daily in the postoperative period.

Evaluation of Potential Effects of Increased Outdoor Temperatures Due to Global Warming on Cerebral Blood Flow Rate and Respiratory Function in Chronic Obstructive Disease and Anemia.

Global warming due to increased outdoor carbon dioxide (CO2) levels may cause several health problems such as headaches, cognitive impairment, or kidney dysfunction. It is predicted that further increases in CO2 levels will increase the morbidity and mortality of patients affected by a variety of diseases. For instance, patients with Chronic Obstructive Pulmonary Disease (COPD) may suffer cognitive impairments or intracranial bleeding due to an increased cerebral blood flow rate. Predicting the harmful effects of global warming on human health will help to take measures for potential problems. Therefore, the quantification of physiological parameters is an essential step to investigate the effects of global warming on human health. In this study, the effects of increased outdoor temperatures due to climate change on cerebral blood flow rate and respiratory function in healthy subjects and COPD patients with anemia and respiratory acidosis are evaluated utilizing numerical simulations. The numerical model simulates cardiac function and blood circulation in systemic, pulmonary and cerebral circulations, cerebral autoregulatory functions, respiratory function, alveolar gas exchange, oxygen (O2) and CO2 contents, and hemoglobin levels in the blood. The simulation results show that although the cardiovascular function is not significantly altered, the respiratory function and cerebral blood flow rates are altered remarkably.

Relative Hypoxemia at Depth During Breath-Hold Diving Investigated Through Arterial Blood Gas Analysis and Lung Ultrasound.

Pulmonary gas exchange in breath-hold diving (BHD) consists of a progressive increase in arterial PO2 and PCO2 (PaO2 and PaCO2) during descent. However, recent findings have demonstrated that PaO2 does not consistently rise in all subjects. This study aimed at verifying and explaining PaO2 derangements during BHD analyzing arterial blood gases and searching for pulmonary alterations with lung ultrasound. After ethical approval, 14 fit breath-hold divers were included. Experiments were performed in warm water (temperature: 31°C). We analyzed arterial blood gases immediately before, at depth, and immediately after a breath-hold dive - to -15 meters of fresh water (mfw) and -42 mfw. Signs of lung interstitial edema and atelectasis were searched simultaneously with a marinized lung ultrasound. In 5 subjects (-15 mfw) and 4 subjects (-42 mfw) the PaO2 at depth seems to decrease instead of increasing. PaCO2 and lactate showed slight variations. At depth, no lung ultrasound alterations were seen except in one subject (hypoxemia and B-lines at -15 mfw; B-lines at the surface). Lung interstitial edema was detected in 3 and 12 subjects after resurfacing from -15 mfw and -42 mfw, respectively. Two subjects developed hypoxemia at depth and a small lung atelectasis (a focal pleural irregularity of triangular shape, surrounded by thickened B lines) after resurfacing from -42 mfw. Current experiments confirmed that some BH divers can experience hypoxemia at depth. The hypothesized explanation for such a discrepancy is lung atelectasis, which could not be detected in all subjects probably due to limited time available at depth.

A modal definition of ideal alveolar oxygen.

In the three-compartment model of lung ventilation-perfusion heterogeneity (VA/Q scatter), both Bohr dead space and shunt equations require values for central "ideal" compartment O2 and CO2 partial pressures. However, the ideal alveolar gas equation most accurately calculates mixed (ideal and alveolar dead space) PAO2 . A novel "modal" definition has been validated for ideal alveolar CO2 partial pressure, at the VA/Q ratio in a lung distribution where CO2 elimination is maximal. A multicompartment computer model of physiological, lognormal distributions of VA and Q was used to identify modal "ideal" PAO2 , and find a modification of the alveolar gas equation to estimate it across a wide range of severity of VA/Q heterogeneity and FIO2 . This was then validated in vivo using data from a study of 36 anesthetized, ventilated patients with FIO2 0.35-80. Substitution in the alveolar gas equation of respiratory exchange ratio R with achieved excellent agreement (r2 = 0.999) between the calculated ideal PAO2 and the alveolar-capillary Pc'O2 at the modal VO2 point ("modal" Pc'O2 ), across a range of log standard deviation of VA 0.25-1.75, true shunt 0%-20%, overall VA/Q 0.4-1.6, and FIO2 0.18-1.0, where the modeled PaO2 was over 50 mm Hg. Modal ideal PAO2 can be reliably estimated using routine blood gas measurements.

Current definitions of the breathing cycle in alveolar breath-by-breath gas exchange analysis.

Identification of the breathing cycle forms the basis of any breath-by-breath gas exchange analysis. Classically, the breathing cycle is defined as the time interval between the beginning of two consecutive inspiration phases. Based on this definition, several research groups have developed algorithms designed to estimate the volume and rate of gas transferred across the alveolar membrane ("alveolar gas exchange"); however, most algorithms require measurement of lung volume at the beginning of the ith breath (VLi-1; i.e., the end-expiratory lung volume of the preceding ith breath). The main limitation of these algorithms is that direct measurement of VLi-1 is challenging and often unavailable. Two solutions avoid the requirement to measure VLi-1 by redefining the breathing cycle. One method defines the breathing cycle as the time between two equal fractional concentrations of lung expired oxygen (Fo2) (or carbon dioxide; Fco2), typically in the alveolar phase, whereas the other uses the time between equal values of the Fo2/Fn2 (or Fco2/Fn2) ratios [i.e., the ratio of fractional concentrations of lung expired O2 (or CO2) and nitrogen (N2)]. Thus, these methods identify the breathing cycle by analyzing the gas fraction traces rather than the gas flow signal. In this review, we define the traditional approach and two alternative definitions of the human breathing cycle and present the rationale for redefining this term. We also explore the strengths and limitations of the available approaches and provide implications for future studies.

Senescence of alveolar epithelial progenitor cells: a critical driver of lung fibrosis.

Pulmonary fibrosis comprises a range of chronic interstitial lung diseases (ILDs) that impose a significant burden on patients and public health. Among these, idiopathic pulmonary fibrosis (IPF), a disease of aging, is the most common and most severe form of ILD and is treated largely by lung transplantation. The lack of effective treatments to stop or reverse lung fibrosis-in fact, fibrosis in most organs-has sparked the need to understand causative mechanisms with the goal of identifying critical points for potential therapeutic intervention. Findings from many groups have indicated that repeated injury to the alveolar epithelium-where gas exchange occurs-leads to stem cell exhaustion and impaired alveolar repair that, in turn, triggers the onset and progression of fibrosis. Cellular senescence of alveolar epithelial progenitors is a critical cause of stemness failure. Hence, senescence impairs repair and thus contributes significantly to fibrosis. In this review, we discuss recent evidence indicating that senescence of epithelial progenitor cells impairs alveolar homeostasis and repair creating a profibrotic environment. Moreover, we discuss the impact of senescent alveolar epithelial progenitors, alveolar type 2 (AT2) cells, and AT2-derived transitional epithelial cells in fibrosis. Emerging evidence indicates that transitional epithelial cells are prone to senescence and, hence, are a new player involved in senescence-associated lung fibrosis. Understanding the complex interplay of cell types and cellular regulatory factors contributing to alveolar epithelial progenitor senescence will be crucial to developing targeted therapies to mitigate their downstream profibrotic sequelae and to promote normal alveolar repair.NEW & NOTEWORTHY With an aging population, lung fibrotic diseases are becoming a global health burden. Dysfunctional repair of the alveolar epithelium is a key causative process that initiates lung fibrosis. Normal alveolar regeneration relies on functional progenitor cells; however, the senescence of these cells, which increases with age, hinders their ability to contribute to repair. Here, we discuss studies on the control and consequence of progenitor cell senescence in fibrosis and opportunities for research.

The Tritube: Facilitating Upper Airway Surgery With an Ultrathin Cuffed Airway Device.

The Tritube is a narrow-bore cuffed tracheal tube (outer diameter 4.4 mm and inner diameter ~2.4 mm) that permits effective alveolar gas exchange using flow-controlled ventilation. Constant gas flow delivers physiological minute volumes, within preset pressure limits, and applies suction to the airway during expiration. The technique has attracted interest for laryngotracheal microsurgery as it provides superior surgical exposure and avoids many of the complications associated with high-frequency jet ventilation. Cuff inflation protects the lower airway and produces a motionless operating field. We describe the structure of the device, discuss its benefits, and suggest how it should be used clinically.