Alveolar-arterial Gradient Research Articles

Fetal haemoglobin and oxygen requirement in preterm infants: an observational study

ObjectiveTo investigate the relationship between the fraction of fetal haemoglobin (HbF(%)) and oxygen requirement as determined by the fraction of inspired oxygen (FiO2) and alveolar–arterial gradient (A–a gradient). Increased alveolar...

Cardiopulmonary exercise testing excludes significant disease in patients recovering from COVID-19

ObjectivePost-COVID-19 syndrome presents a health and economic challenge affecting ~10% of patients recovering from COVID-19. Accurate assessment of patients with post-COVID-19 syndrome is complicated by health anxiety and coincident symptomatic...

Hepatopulmonary Syndrome: A Comprehensive Review.

Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. This condition results from intricate interactions between the liver, the gastrointestinal system, and the lungs. This complex system primarily affects pulmonary endothelial, immunomodulatory, and respiratory epithelial cells. Consequently, this contributes to pathological pulmonary changes characteristic of HPS. A classification system based on the severity of oxygen deficiency has been proposed for grading the physiological dysfunction of HPS. Contrast-enhanced echocardiography is considered the primary radiological evaluation for identifying abnormal blood vessel dilations within the lungs, which, combined with an elevated alveolar-arterial gradient, is essential for making the diagnosis. Liver transplantation is the sole effective definitive treatment that can reverse the course of the condition. Despite often being symptomless, HPS carries a significant risk of mortality before transplantation, regardless of the severity of liver disease. Meanwhile, there is varying data regarding survival rates following liver transplantation. The adoption of the model for end-stage liver disease (MELD) standard exception policy has notably improved the results for individuals with HPScompared to the period before MELD was introduced. This review offers a summary of the present understanding, highlighting recent advancements in the diagnosis and treatment of HPS. Furthermore, it aims to augment comprehension of the condition's fundamental mechanisms through insights derived from experimental models and translational research.

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.

Clinical prediction for surgical versus nonsurgical interventions in patients with vertebral osteomyelitis and discitis.

Vertebral osteomyelitis and discitis (VOD), an infection of intervertebral discs, often requires spine surgical intervention and timely management to prevent adverse outcomes. Our study aims to develop a machine learning (ML) model to predict the indication for surgical intervention (during the same hospital stay) versus nonsurgical management in patients with VOD. This retrospective study included adult patients (≥18 years) with VOD (ICD-10 diagnosis codes M46.2,3,4,5) treated at a single institution between 01/01/2015 and 12/31/2019. The primary outcome studied was surgery. Candidate predictors were age, sex, race, Elixhauser comorbidity index, first-recorded lab values, first-recorded vital signs, and admit diagnosis. After splitting the dataset, XGBoost, logistic regression, and K-neighbor classifier algorithms were trained and tested for model development. A total of 1,111 patients were included in this study, among which 30% (n=339) of patients underwent surgical intervention. Age and sex did not significantly differ between the two groups; however, race did significantly differ (P<0.0001), with the surgical group having a higher percentage of white patients. The top ten model features for the best-performing model (XGBoost) were as follows (in descending order of importance): admit diagnosis of fever, negative culture, Staphylococcus aureus culture, partial pressure of arterial oxygen to fractional inspired oxygen ratio (PaO2:FiO2), admit diagnosis of intraspinal abscess and granuloma, admit diagnosis of sepsis, race, troponin I, acid-fast bacillus culture, and alveolar-arterial gradient (A-a gradient). XGBoost model metrics were as follows: accuracy =0.7534, sensitivity =0.7436, specificity =0.7586, and area under the curve (AUC) =0.8210. The XGBoost model reliably predicts the indication for surgical intervention based on several readily available patient demographic information and clinical features. The interpretability of a supervised ML model provides robust insight into patient outcomes. Furthermore, it paves the way for the development of an efficient hospital resource allocation instrument, designed to guide clinical suggestions.

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

Hypercapnia is not excluded by normoxia in neuromuscular disease patients: implications for oximetry.

Pulse oximetry is widely used in the assessment of chronic respiratory failure in neuromuscular disease (NMD) patients. Chronic respiratory failure is the major cause of morbidity and mortality, necessitating early diagnosis and intervention. Guidelines suggest that an arterial blood gas (ABG) measurement is indicated if oxygen saturation (S pO2 ) is ≤94% in the absence of lung disease. However, hypercapnia with normoxia (S pO2 ≥95%) has been observed on ABGs of patients with NMD, in particular those with motor neurone disease. A single-centre retrospective audit of room-air ABGs in stable hypercapnic chronic respiratory failure patients from 1990 to 2020 was performed. Patients with parenchymal lung disease were excluded. Patients were grouped into three main categories: non-NMD, other NMD and motor neurone disease. 297 ABGs with hypercapnia from 180 patients with extrinsic restrictive lung disease were analysed. No patients with non-NMD, 54% of patients with other NMD and 36% of motor neurone disease patients demonstrated hypercapnia with normoxia (Chi-squared 61.33; p<0.001). The potential mechanism is proposed to be a difference in calculated respiratory quotient. If the alveolar-arterial gradient is assumed to be normal, the calculated respiratory quotient was significantly higher in motor neurone disease patients and other NMD patients compared with non-NMD patients (estimated marginal mean 0.99, 95% CI 0.94-1.03; 0.86 0.76-0.96; 0.73, 0.63-0.83, respectively; p<0.001) by mixed-model analysis. Hypercapnia is not excluded with normal oximetry in NMD patients and may be due to an elevated respiratory quotient. This has implications in the diagnosis and monitoring of respiratory insufficiency in NMD patients with oximetry alone.

A novel prognostic model to predict mortality in patients with acute-on-chronic liver failure in intensive care unit.

Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.

L-cysteine ethylester reverses the adverse effects of morphine on breathing and arterial blood-gas chemistry while minimally affecting antinociception in unanesthetized rats

L-cysteine ethylester (L-CYSee) is a membrane-permeable analogue of L-cysteine with a variety of pharmacological effects. The purpose of this study was to determine the effects of L-CYSee on morphine-induced changes in ventilation, arterial-blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient (i.e., a measure of the index of alveolar gas-exchange), antinociception and sedation in male Sprague Dawley rats. An injection of morphine (10 mg/kg, IV) produced adverse effects on breathing, including sustained decreases in minute ventilation. L-CYSee (500 μmol/kg, IV) given 15 min later immediately reversed the actions of morphine. Another injection of L-CYSee (500 μmol/kg, IV) after 15 min elicited more pronounced excitatory ventilatory responses. L-CYSee (250 or 500 μmol/kg, IV) elicited a rapid and prolonged reversal of the actions of morphine (10 mg/kg, IV) on ABG chemistry (pH, pCO2, pO2, sO2) and A-a gradient. L-serine ethylester (an oxygen atom replaces the sulfur; 500 μmol/kg, IV), was ineffective in all studies. L-CYSee (500 μmol/kg, IV) did not alter morphine (10 mg/kg, IV)-induced sedation, but slightly reduced the overall duration of morphine (5 or 10 mg/kg, IV)-induced analgesia. In summary, L-CYSee rapidly overcame the effects of morphine on breathing and alveolar gas-exchange, while not affecting morphine sedation or early-stage analgesia. The mechanisms by which L-CYSee modulates morphine depression of breathing are unknown, but appear to require thiol-dependent processes.

Single center experience with first-intention high-frequency jet vs. volume-targeted ventilation in extremely preterm neonates.

To examine whether first-intention high-frequency jet ventilation (HFVJ), compared to volume-targeted ventilation (VTV), in extremely preterm infants is associated with lower incidence of bronchopulmonary dysplasia (BPD) and other adverse clinical outcomes. We conducted a retrospective cohort study evaluating neonates with gestational age (GA) ≤28 weeks, who received first-intention HFJV (main exposure) or VTV (comparator), between 11/2020 and 3/2023, with a subgroup analysis including neonates with GA ≤26 weeks and oxygenation index (OI) >5. We identified 117 extremely preterm neonates, 24 (GA 25.2 ± 1.6 weeks) on HFJV, and 93 (GA 26.4 ± 1.5 weeks, p = 0.001) on VTV. The neonates in the HFJV group had higher oxygenation indices on admission, higher inotrope use, and remained intubated for a longer period. Despite these differences, there were no statistically significant differences in rates of BPD, survival, or other adverse outcomes between the two groups. In subgroup analysis of 18 neonates on HFJV and 39 neonates on VTV, no differences were recorded in the GA, and duration of mechanical ventilation, while neonates in the HFJV group had significantly lower rates of BPD (50% compared to 83%, p = 0.034), and no significant differences in other adverse outcomes compared to neonates in the VTV group. In neonates ≤26 weeks of GA with OI >5, HFJV was significantly associated with lower rates of BPD (OR 0.21, 95% CI 0.05-0.92), and combined BPD or death (OR 0.18, 95% CI 0.03-0.85), after adjusting for birth weight, and Arterial-alveolar gradient on admission. In extremely preterm neonates ≤26 weeks of GA with OI >5, first-intention HFJV, in comparison to VTV, is associated with lower rates of BPD.

Variation in leaf photosynthetic capacity within plant canopies: optimization, structural, and physiological constraints and inefficiencies.

Leaf photosynthetic capacity (light-saturated net assimilation rate, AA) increases from bottom to top of plant canopies as the most prominent acclimation response to the conspicuous within-canopy gradients in light availability. Light-dependent variation in AA through plant canopies is associated with changes in key leaf structural (leaf dry mass per unit leaf area), chemical (nitrogen (N) content per area and dry mass, N partitioning between components of photosynthetic machinery), and physiological (stomatal and mesophyll conductance) traits, whereas the contribution of different traits to within-canopy AA gradients varies across sites, species, and plant functional types. Optimality models maximizing canopy carbon gain for a given total canopy N content predict that AA should be proportionally related to canopy light availability. However, comparison of model expectations with experimental data of within-canopy photosynthetic trait variations in representative plant functional types indicates that such proportionality is not observed in real canopies, and AA vs. canopy light relationships are curvilinear. The factors responsible for deviations from full optimality include stronger stomatal and mesophyll diffusion limitations at higher light, reflecting greater water limitations and more robust foliage in higher light. In addition, limits on efficient packing of photosynthetic machinery within leaf structural scaffolding, high costs of N redistribution among leaves, and limited plasticity of N partitioning among components of photosynthesis machinery constrain AA plasticity. Overall, this review highlights that the variation of AA through plant canopies reflects a complex interplay between adjustments of leaf structure and function to multiple environmental drivers, and that AA plasticity is limited by inherent constraints on and trade-offs between structural, chemical, and physiological traits. I conclude that models trying to simulate photosynthesis gradients in plant canopies should consider co-variations among environmental drivers, and the limitation of functional trait variation by physical constraints and include the key trade-offs between structural, chemical, and physiological leaf characteristics.

Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Association between one-session bilateral whole-lung lavage and periprocedural complications in patients with pulmonary alveolar proteinosis: a retrospective cohort study

BackgroundWhole lung lavage (WLL) has been recognized as the most effective therapy of severe pulmonary alveolar proteinosis (PAP). Most centers perform the lavage of each lung in two sessions under general anesthesia at an interval of several days to weeks. Compared with two-session WLL, one-session bilateral sequential WLL only requires general anesthesia once. However, the safety of one-session WLL in PAP patients has not been assessed by large cohort studies. In this study, we aimed to investigate the association between the mode of WLL procedure (one-session or two-session) and the risk of periprocedural complications in PAP patients.MethodsIn this single-center retrospective cohort study, we included adult patients who were diagnosed as PAP and had undergone WLL procedures under general anesthesia from 2000 to 2022. Patients requiring extra-corporeal oxygenation during WLL were excluded. Since some patients received multiple WLL procedures, we considered each procedure in one-session or two-session group as a unique unit in our analysis. The primary outcome was the occurrence of any complications during hospitalization, including termination of WLL procedure due to fluid leakage or refractory hypoxemia, bronchospasm, delayed endotracheal extubation, cardiovascular event, pneumothorax, and fever.ResultsWe included a total of 175 WLL procedures (118 patients), with 48 in the two-session group and 127 in the one-session group. Periprocedural complications occurred in 17 (35.4%) and 39 (30.7%) procedures in the two-session and the one-session groups, respectively. The risk of periprocedural complications did not differ significantly between groups, after adjusting the unbalanced confounders in a multivariable model (odds ratio 0.95, 95% confidence interval 0.34 to 2.69, P 0.929) or by inverse probability of treatment weighting (odds ratio 0.70, 95% confidence interval 0.30 to 1.54, P 0.379). Compared with the two-session WLL group, the one-session WLL group had a shorter postprocedural length of hospitalization and comparable decrease in alveolar-arterial oxygen tension gradient from baseline.ConclusionsOne-session bilateral WLL was not associated with an increased risk of periprocedural complications compared with two-session WLL in PAP patients. Experienced physicians may consider performing one-session WLL in view of the comparable safety and efficacy and potential advantages of saving time.

Relationships Between Systemic Inflammation, Intestinal Damage and Postoperative Organ Dysfunction in Adults Undergoing Low-Risk Cardiac Surgery.

Approximately half of patients who undergo cardiac surgery develop systemic inflammatory response syndrome. Extracorporeal circulation and intestinal injury may play a role in this inflammatory response, although their relative contributions remain elusive. Moreover, it is largely unknown to what extent these factors contribute to cardiac surgery-induced postoperative organ dysfunction. In this secondary analysis, we measured circulating levels of the intestinal damage marker intestinal fatty acid binding protein (I-FABP) and of the inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, IL-1RA, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β in 180 patients undergoing on-pump cardiac surgery. The average Z-score of levels of the different cytokines was used as an integral measure of the cytokine response. Relationships between duration of extracorporeal circulation, extent of intestinal injury, inflammation, and postoperative organ dysfunction were explored. Plasma I-FABP levels increased during surgery, with peak levels observed at the end of cardiopulmonary bypass (CPB). Except for TNF-α, the levels of all cytokines increased during surgery, with peak levels observed either 2 (MCP-1, MIP-1α, and MIP-1β), 4 (IL-6, IL-8, and IL-1RA) or 6 (IL-10) hours after the end of CPB. While the duration of CPB significantly correlated with cytokine Z-score (r=0.544, p<0.05), no relationship with I-FABP levels was found. Furthermore, no significant correlations between I-FABP and cytokine levels were observed. The duration of CPB correlated with a deterioration in postoperative kidney function (estimated glomerular filtration rate [eGFR]) and troponin levels. Cytokine Z-score was associated with postoperative troponin levels, fluid administration, inotropic score, pulmonary alveolar-arterial gradient on the first postoperative morning, and deterioration of kidney function (eGFR). I-FABP levels did not correlate with any of the cardiovascular, pulmonary, or renal parameters. In patients undergoing low-risk cardiac surgery, the duration of CPB represents an important determinant of the systemic cytokine response, whereas both the CPB duration and the systemic inflammatory response contribute to subsequent organ dysfunction. Intestinal damage does not appear to play a relevant role in the postoperative inflammatory response and development of postoperative organ dysfunction in these patients.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. ClinicalTrial.gov, identifier: NCT04516577.

Recurrent cyanotic spells in an octogenarian

We report rare case of an octogenarian who, after years of diagnostic delay, was found to have a patent foramen ovale, and due to an ascending aortic aneurysm that anatomically facilitated right-to-left shunt, presenting with life-threatening cyanotic attacks. The characteristic orthodeoxia-platypnea syndrome and high alveolar arterial gradient hint to the diagnosis. She was eventually treated successfully with urgent percutaneous PFO closure. Routine ordering of a transthoracic echocardiogram, without agitated saline injection under provocation maneuvers, may not be sufficient to rule out shunts.

Severe asthma, more than that?

I was recently invited to write about the development of asthma management in the past decade. Biologic therapy came to my mind, and I was fascinated by the concept that asthma remission can potentially be achieved with this treatment (https://erj.ersjournals.com/content/early/2022/03/17/13993003.02583-2021). At the same time, I reflected on the management of one of my patients with severe asthma treated with biologics and the importance of looking for and managing comorbidities when treating patients with severe asthma. She was a young lady, and it was after more than a year of treatment with various agents for severe asthma, including high-dose inhaled corticosteroids, long-acting beta-agonist, anti-muscarinic agent, montelukast, azithromycin, systemic steroid and biologics (two biologics, started with one and then changed to the other with lack of effect) that we made the diagnosis of inducible laryngeal obstruction (ILO) (https://erj.ersjournals.com/content/50/3/1602221) that was causing the recurrent ‘asthma exacerbations’ and ICU admissions. Correct diagnosis is crucial for the treatment of asthma. However, having a confirmed diagnosis of asthma does not mean that it is the sole cause of respiratory symptoms/asthma exacerbations. This lady had features typical of asthma, including positive bronchodilator reversibility and her lung function varied with time with lower FEV1 at times of poor control or attacks. She also had Type-2 high asthma with high eosinophil blood count and exhaled nitric oxide levels. At the start of the illness, the patient improved with systemic steroid during hospitalisations. We did our usual workup for assessing comorbidities, such as looking for rhinitis and gastroesophageal reflux disease and excluded eosinophilic granulomatosis with polyangiitis. However, the young lady subsequently had more ‘asthma attacks’, and those episodes required ICU care, but no intubation was ever needed. Given the recurrent ICU admissions despite optimal pharmacotherapy for asthma, we have performed extensive investigations to exclude other diseases, including CT thorax, blood tests, echocardiogram and sleep study. During one of the ICU admissions, the patient was noted to have a low tidal and a high respiratory rate while on non-invasive pressure ventilation (NIV). Arterial blood gas taken during the ‘attacks’ showed respiratory acidosis with elevated pCO2 and normal alveolar-arterial gradient. The ‘attacks’ did not improve with asthma medications but responded to oxygen supplementation and NIV. We suspected ILO and were able to prove that by laryngoscopy. The patient had several ‘attacks’ of breathlessness afterwards, which were improved by benzodiazepines. We have thus stopped the unnecessary asthma medications for this patient, including biologics. The ILO was managed by speech therapist, psychologist, psychiatrist and ENT surgeon. Not every patient needs extensive investigations to search for comorbidities, but how far we need to go for patients with recurrent ‘asthma attacks’ would need clinical judgement and a personalized approach. Also, we have to think about ILO earlier in patients with severe asthma not responding well to therapy. We currently have potent medications, including biologics, for treating severe asthma, but we must ensure that these are given to the right patient. None declared.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19

BackgroundCardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae.MethodsIn this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed.ResultsTwelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V′O2) considered within normal limits (median peak predicted O2 uptake (V′O2) of 98% [87.2–106.3]). Length of ICU stay remained an independent predictor of V′O2. More than half of the patients with a normal peak predicted V′O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21–0.32] at anaerobic threshold (AT) and 0.29 [0.25–0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2–44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = − 0.15; p = 0.01).ConclusionsTwelve months after severe COVID-19 pneumonia, most of the patients had a peak V′O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea.Trial registration: NCT04519320 (19/08/2020).

Effects of three immobilizing drug combinations on ventilation, gas exchange and metabolism in free-living African lions (Panthera leo).

Free-living lions (12 per group) were immobilized with tiletamine-zolazepam-medetomidine (TZM), ketamine-medetomidine (KM), or ketamine-butorphanol-medetomidine (KBM). During immobilization, respiratory, blood gas and acid-base variables were monitored for 30minutes. Respiratory rates were within expected ranges and remained constant throughout the immobilizations. Ventilation increased in lions over the immobilization period from 27.2 ± 9.5 to 35.1 ± 25.4L/min (TZM), 26.1 ± 14.3 to 28.4 ± 18.4L/min (KM) and 23.2 ± 10.8 to 26.7 ± 14.2L/min (KBM). Tidal volume increased over the immobilization period from 1800 ± 710 to 2380 ± 1930mL/breath (TZM), 1580 ± 470 to 1640 ± 500mL/breath (KM) and 1600 ± 730 to 1820 ± 880mL/breath (KBM). Carbon dioxide production was initially lower in KBM (0.4 ± 0.2L/min) than in TZM (0.5 ± 0.2L/min) lions but increased over time in all groups. Oxygen consumption was 0.6 ± 0.2L/min (TZM), 0.5 ± 0.2L/min (KM) and 0.5 ± 0.2L/min (KBM) and remained constant throughout the immobilization period. Initially the partial pressure of arterial oxygen was lower in KBM (74.0 ± 7.8mmHg) than in TZM (78.5 ± 4.7mmHg) lions, but increased to within expected range in all groups over time. The partial pressure of arterial carbon dioxide was higher throughout the immobilizations in KBM (34.5 ± 4.2mmHg) than in TZM (32.6 ± 2.2mmHg) and KM (32.6 ± 3.8mmHg) lions. Alveolar-arterial gradients were initially elevated, but decreased over time for all groups, although in KM lions it remained elevated (26.9 ± 10.4mmHg) above the expected normal. Overall, all three drug combinations caused minor respiratory and metabolic side-effects in the immobilized lions. However, initially hypoxaemia occurred as the drug combinations, and possibly the stress induced by the immobilization procedure, hinder alveoli oxygen gas exchange.

Preliminary study evaluating the assessment of changes in pulmonary function associated with body positioning in dogs with suspected aspiration pneumonia.

To evaluate the variability in arterial blood gas (ABG) assessment of pulmonary function with different body positioning in dogs with suspected aspiration pneumonia. The median differences in alveolar-arterial gradient, Pao2 , and Paco2 values in different recumbencies were not statistically significantly different, both within patients and across the study population. No difference was noted in ABG values in the subgroups with unilateral or bilateral disease or that were more affected on the right side versus the left side. This preliminary study provides data that can be used to calculate appropriate sample sizes for subsequent studies investigating the impact of recumbency on pulmonary function in patients with aspiration pneumonia.