Lung mechanics in juvenile and adult Chelonoidis carbonarius (Spix, 1824).

Testudines possess a rigid shell that influences the mechanics of the respiratory system. We studied respiratory mechanics in the terrestrial red-footed tortoise Chelonoidis carbonarius (Cryptodira), comparing juvenile individuals with a less ossified and more flexible carapace to adults with a well-ossified rigid shell. Combined with these ontogenetic differences, we analyzed respiratory system mechanics with animals in a supine and a prone position, as well as in the isolated lungs, to evaluate the impact of the viscera onto breathing mechanics. To do so, we used established protocols to measure pulmonary volumes (i.e., resting, VLr; and maximum, VLm), static (Cstat) and dynamic (Cdyn) compliances, and the work of breathing (W). We observed that isolated lungs displayed increased VLr, VLm, Cstat,Cdyn and decreased W. Additionally, pulmonary volumes, compliances, and W were affected by evaluated positions, such as a smaller VLr in a supine position. Cdyn and W showed a volume dependency while frequency had less influence on these variables. At similar levels of ventilation, juveniles showed a lower W than adults when standardized by body mass, but similar W when standardized by VLr. Clear ontogenetic changes could be observed in breathing mechanics between juvenile and adult C. carbonarius. While these differences might largely be explained by variations in shell ossifications, other explanations such as differences in visceral proportions or developmental degree of the post-pulmonary septum should also be taken into account.

Implications of chronic hypoxia during development in red drum.

Respiratory plasticity is a beneficial response to chronic hypoxia in fish. Red drum, a teleost that commonly experiences hypoxia in the Gulf of Mexico, have shown respiratory plasticity following sublethal hypoxia exposure as juveniles, but implications of hypoxia exposure during development are unknown. We exposed red drum embryos to hypoxia (40% air saturation) or normoxia (100% air saturation) for 3 days post fertilization (dpf). This time frame encompasses hatch and exogenous feeding. At 3 dpf, there was no difference in survival or changes in size. After the 3-day hypoxia exposure, all larvae were moved and reared in common normoxic conditions. Fish were reared for ∼3 months and effects of the developmental hypoxia exposure on swim performance and whole-animal aerobic metabolism were measured. We used a cross design wherein fish from normoxia (N=24) were exercised in swim tunnels in both hypoxia (40%, n=12) and normoxia (100%, n=12) conditions, and likewise for hypoxia-exposed fish (n=10 in each group). Oxygen consumption, critical swim speed (Ucrit), critical oxygen threshold (Pcrit) and mitochondrial respiration were measured. Hypoxia-exposed fish had higher aerobic scope, maximum metabolic rate, and higher liver mitochondrial efficiency relative to control fish in normoxia. Interestingly, hypoxia-exposed fish showed increased hypoxia sensitivity (higher Pcrit) and recruited burst swimming at lower swim speeds relative to control fish. These data provide evidence that early hypoxia exposure leads to a complex response in later life.

Pre-oxygenation using high-flow nasal oxygen versus tight facemask in trauma patients undergoing emergency anaesthesia.

BACKGROUND: Patients suffering from major traumatic injuries frequently require emergency anaesthesia. Due to often compromised physiology and the time-sensitive management, trauma patients may be more prone to desaturate during induction of anaesthesia. We hypothesised that pre-oxygenation using high-flow nasal oxygen would decrease the risk of desaturation during induction of anaesthesia in trauma patients and the study therefore aimed to compare the frequency of desaturation when pre-oxygenation was performed with high-flow nasal oxygen or a traditional facemask. METHODS: This exploratory, prospective, before-and-after study was conducted at the Karolinska University Hospital, Sweden. Adult (≥18 years of age) patients suffering major traumatic injuries needing emergency anaesthesia were included around the clock. Patients were pre-oxygenated using a tight-fitting facemask during the first nine months of enrollment. High-flow nasal oxygen was then introduced as a method for pre-oxygenation of trauma patients. The primary outcome was the proportion of patients desaturating <93% during induction of anaesthesia, assessed from the start of pre-oxygenation until one minute after intubation. Secondary outcomes included perceived difficulty of pre-oxygenation among anaesthetists (assessed on a scale between 1 and 10) and safety outcomes, such as incidence of regurgitations and intracranial gas (assessed radiologically). RESULTS: Data from 96 patients were analysed. Facemask pre-oxygenation was performed in 66 patients, while 30 patients were pre-oxygenated with high-flow nasal oxygen. The most frequent trauma mechanisms were stabbing injuries (n = 34 (35%)) and fall injuries (n = 21 (22%)). There were no differences in patient characteristics between the groups. Eight (12%) versus three (10%) patients desaturated <93% in the facemask and high-flow nasal oxygen group respectively, OR 0.81 (95% CI 0.20-3.28), p = .76. Anaesthetists assessed pre-oxygenation using high-flow nasal oxygen as easier compared to facemask pre-oxygenation. No patient in any group showed signs of regurgitation. Among patients with facial or skull fractures requiring anaesthesia before radiology was performed, intracranial gas was seen in four (40%) patients pre-oxygenated with a facemask and in no patient pre-oxygenated with HFNO (p = .23). CONCLUSION: In this prospective study investigating trauma patients undergoing emergency anaesthesia, we could not see any difference in the number of patients desaturating when pre-oxygenation was performed with high-flow nasal oxygen compared to a tight-fitting facemask. Pre-oxygenation using high-flow nasal oxygen was assessed as easier compared to facemask pre-oxygenation.

The Effects of Diabetes on Gas Transfer Capacity, Lung Volumes, Muscle Strength, and Cardio-pulmonary Responses During Exercise.

BACKGROUND: Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity? METHODS: Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories. RESULTS: 40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27 kg/m2). The presence of diabetes was independently associated with a reduction in FEV1 (- 130 ml), FVC (- 220 ml), DLCO (- 1.52 ml/min/mmHg), and VA (- 340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI. CONCLUSION: The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI.

Hypoxia-acclimation adjusts skeletal muscle anaerobic metabolism and burst swim performance in a marine fish.

Red drum, Sciaenops ocellatus, are a marine teleost native to the Gulf of Mexico that routinely experiences periods of low oxygen (hypoxia). Recent work has demonstrated this species has the capacity to improve aerobic performance in hypoxia through respiratory acclimation. However, it remains unknown how hypoxia acclimation impacts anaerobic metabolism in red drum, and the consequences of exhaustive exercise and recovery. Juvenile fish were acclimated to normoxia (n = 15, DO 90.4 ± 6.42 %) or hypoxia (n = 15, DO 33.6 ± 7.2 %) for 8 days then sampled at three time points: at rest, after exercise, and after a 3 h recovery period. The resting time point was used to characterize the acclimated phenotype, while the remaining time points demonstrate how this phenotype responds to exhaustive exercise. Whole blood, red muscle, white muscle, and heart tissues were sampled for metabolites and enzyme activity. The resting phenotype was characterized by lower pHe and changes to skeletal muscle ATP. Exhaustive exercise increased muscle lactate, and decreased phosphocreatine and ATP with no effect of acclimation. Interestingly, hypoxia-acclimated fish had higher pHe and pHi than control in all exercise time points. Red muscle ATP was lower in hypoxia-acclimated fish versus control at each sample period. Moreover, acclimated fish increased lactate dehydrogenase activity in the red muscle. Hypoxia acclimation increased white muscle ATP and hexokinase activity, a glycolytic enzyme. In a gait-transition swim test, hypoxia-acclimated fish recruited anaerobic-powered burst swimming at lower speeds in normoxia compared to control fish. These data suggest that acclimation increases reliance on anaerobic metabolism, and does not benefit recovery from exhaustive exercise.

State of the art: Monitoring of the respiratory system during veno-venous extracorporeal membrane oxygenation.

Monitoring the patient receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging due to the complex physiological interplay between native and membrane lung. Understanding these interactions is essential to understand the utility and limitations of different approaches to respiratory monitoring during ECMO. We present a summary of the underlying physiology of native and membrane lung gas exchange and describe different tools for titrating and monitoring gas exchange during ECMO. However, the most important role of VV ECMO in severe respiratory failure is as a means of avoiding further ergotrauma. Although optimal respiratory management during ECMO has not been defined, over the last decade there have been advances in multimodal respiratory assessment which have the potential to guide care. We describe a combination of imaging, ventilator-derived or invasive lung mechanic assessments as a means to individualise management during ECMO.

The fourth dimension: physiological resilience as an independent determinant of endurance exercise performance.

Endurance exercise performance is known to be closely associated with the three physiological pillars of maximal O2 uptake ( V ̇ O 2 max $\dot{V}_{{\rm O}_{2}{\rm max}}$ ), economy or efficiency during submaximal exercise, and the fractional utilisation of V ̇ O 2 max $\dot{V}_{{\rm O}_{2}{\rm max}}$ (linked to metabolic/lactate threshold phenomena). However, while 'start line' values of these variables are collectively useful in predicting performance in endurance events such as the marathon, it is not widely appreciated that these variables are not static but are prone to significant deterioration as fatiguing endurance exercise proceeds. For example, the 'critical power' (CP), which is a composite of the highest achievable steady-state oxidative metabolic rate and efficiency (O2 cost per watt), may fall by an average of 10% following 2 h of heavy intensity cycle exercise. Even more striking is that the extent of this deterioration displays appreciable inter-individual variability, with changes in CP ranging from <1% to ∼32%. The mechanistic basis for such differences in fatigue resistance or 'physiological resilience' are not resolved. However, resilience may be important in explaining superlative endurance performance and it has implications for the physiological evaluation of athletes and the design of interventions to enhance performance. This article presents new information concerning the dynamic plasticity of the three 'traditional' physiological variables and argues that physiological resilience should be considered as an additional component, or fourth dimension, in models of endurance exercise performance.

Regional associations between inspiratory tongue dilatory movement and genioglossus activity during wakefulness in people with obstructive sleep apnoea.

Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea-hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta = 0.089, 95% CI [0.000, 0.178], t(99) = 1.995, P = 0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta = -0.123, 95% CI [-0.224, -0.022], t(43) = -2.458, P = 0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P = 0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co-activation of other airway dilator muscles. KEY POINTS: Inspiratory tongue movement is thought to be mediated through changes in genioglossus activity. However, it is unknown if this relationship is altered by obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue movement, quantified with tagged magnetic resonance imaging (MRI), and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in four tongue compartments of people with and without OSA. Larger tongue anterior (dilatory) movement was associated with higher phasic genioglossus EMG for 68% of compartments. OSA participants had an ∼7-times higher odds of having at least one compartment for which a larger anterior tongue movement was not associated with a higher phasic EMG than controls. Therefore, higher genioglossus phasic EMG does not consistently translate into tongue dilatory movement, particularly in people with OSA. Large dilatory tongue movements can occur despite minimal genioglossus inspiratory activity, suggesting co-activation of other pharyngeal muscles.

Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants.

Extremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline boluses to manage hypotension is a common practice in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analyzed ventilator mechanics data in infants managed by conventional mechanical ventilation and administered normal saline bolus for clinical reasons. Data were downloaded for 30 min prebolus, 60 min during the bolus followed by 30 min postbolus. Sixteen infants (mean gestational age 25.2 ± 1 wk and birth weight 620 ± 60 g) were administered 10 mL/kg normal saline over 60 min. The most common clinical indication for saline was hypotension. No significant increase was noted in mean blood pressure after the saline bolus. A significant reduction in pulmonary compliance (mL/cmH2O/kg) was noted (0.43 ± 0.07 vs. 0.38 ± 0.07 vs. 0.33 ± 0.07, P = 0.003, ANOVA). This was accompanied by an elevation in the required peak inspiratory pressure to deliver set volume-guarantee (19 ± 2 vs. 22 ± 2 vs. 22 ± 3 mmHg, P < 0.0001, ANOVA), resulting in a higher respiratory severity score. Normal saline infusion therapy was associated with adverse pulmonary mechanics. Relevant pathophysiologic mechanisms might include translocation of fluid across pulmonary capillaries affected by low vascular tone and heightened permeability in extremes of prematurity, back-pressure effects from raised left atrial volume due to immature left-ventricular myocardium; complemented by the effect of cytokine release from positive pressure ventilation.NEW & NOTEWORTHY Administration of saline boluses is common in premature infants although hypovolemia is an uncommon underlying cause of hypotension. This crystalloid can redistribute into pulmonary interstitial space. In the presence of an immature myocardium and diastolic dysfunction, excess fluid can also be "edemagenic." This study on extremely premature infants (25 wk gestation) noted adverse influence on respiratory physiology after saline infusion. Clinicians need to choose judiciously and reconsider routine use of saline boluses in premature infants.

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms.

Quetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses 'off-label' in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps.

A Longitudinal Study of Respiratory Mechanics in Pregnant Women with Obesity and Overweight.

PURPOSE: Respiratory mechanics and the role of sex hormones in pregnancy are not well elucidated. We examined longitudinal and positional changes in lung mechanics in pregnancy and investigated the role of sex hormones. METHODS: A longitudinal study enrolled 135 women with obesity in early pregnancy. Fifty-nine percent of women identified as White; median body mass index at enrollment was 34.4 kg/m2. Women with respiratory disease were excluded. We obtained measurements of airway resistance and respiratory system reactance in various positions using impedance oscillometry and sex hormones in early and late pregnancy. RESULTS: With pregnancy progression, there was a significant increase in resonant frequency (Fres) (p = 0.012), integrated area of low frequency reactance (AX) (p = 0.0012) and R5-R20Hz (p = 0.038) in the seated position, and a significant increase in R5Hz (p = 0.000), Fres (p = 0.001), AX (p < 0.001 = 0.000), and R5-R20Hz (p = 0.014) in the supine position. Compared to the seated position, the supine position was associated with a significant increase in R5Hz, R20Hz, X5Hz, Fres, and AX in early (p-values < 0.026) and late pregnancy (p-values ≤ 0.001). Changes in progesterone levels between early and late pregnancy predicted the change in R5, Fres, and AX (p-values ≤ 0.043). CONCLUSION: Resistive and elastic loads increase with pregnancy progression and a change in body position from seated to supine increases resistive and elastic loads in both early and late pregnancies. The increase in airway resistance is primarily related to an increase in peripheral rather than central airways resistance. There was an association between the change in progesterone levels and airway resistance.

Opioid Use Disorder, Sleep Deficiency, and Ventilatory Control: Bidirectional Mechanisms and Therapeutic Targets.

Opioid use continues to rise globally. So too do the associated adverse consequences. Opioid use disorder (OUD) is a chronic and relapsing brain disease characterized by loss of control over opioid use and impairments in cognitive function, mood, pain perception, and autonomic activity. Sleep deficiency, a term that encompasses insufficient or disrupted sleep due to multiple potential causes, including sleep disorders, circadian disruption, and poor sleep quality or structure due to other medical conditions and pain, is present in 75% of patients with OUD. Sleep deficiency accompanies OUD across the spectrum of this addiction. The focus of this concise clinical review is to highlight the bidirectional mechanisms between OUD and sleep deficiency and the potential to target sleep deficiency with therapeutic interventions to promote long-term, healthy recovery among patients in OUD treatment. In addition, current knowledge on the effects of opioids on sleep quality, sleep architecture, sleep-disordered breathing, sleep apnea endotypes, ventilatory control, and implications for therapy and clinical practice are highlighted. Finally, an actionable research agenda is provided to evaluate the basic mechanisms of the relationship between sleep deficiency and OUD and the potential for behavioral, pharmacologic, and positive airway pressure treatments targeting sleep deficiency to improve OUD treatment outcomes.

Integration of respiratory physiology and clinical reasoning in the early years of a medical curriculum: engaging with students in a large classroom setting.

Medical graduates are expected to apply scientific principles and explain the processes underlying common and important diseases. Evidence shows that integrated medical curricula, which deliver biomedical science within the context of clinical cases, facilitate student learning in preparation for practice. However, research has also shown that the student's perception of their knowledge can be lower in integrated compared to traditional courses. Thus the development of teaching methods to support both integrated learning and build student confidence in clinical reasoning is a priority. In this study, we describe the use of an audience response system to support active learning in large classes. Sessions, delivered by medical faculty from both academic and clinical backgrounds, were designed to build on the knowledge of the respiratory system in both health and disease through the interpretation of clinical cases. Results showed that student engagement was high throughout the session and students strongly agreed that the application of knowledge to real-life cases was a better way to understand clinical reasoning. Qualitative free text comments revealed that students liked the link between theory and practice and the active, integrated method of learning. In summary, this study describes a relatively simple but highly effective way of delivering integrated medical science teaching, in this case respiratory medicine, to improve student confidence in clinical reasoning. This educational approach was applied within the early years of the curriculum in preparation for teaching within a hospital setting, but the format could be applied across many different settings.NEW & NOTEWORTHY The development of teaching methods that support integrated learning and build student confidence is a priority. An audience response system was used to engage early year medical students in large classes in preparation for teaching within a hospital setting. Results showed high levels of student engagement and a greater appreciation for the link between theory and practice. This study describes a simple, active, and integrated method of learning that improves student confidence in clinical reasoning.

DIAPHRAGM FUNCTION IN CHILDREN WITH ACUTE HYPOXEMIC RESPIRATORY FAILURE: THE PROSPECTIVE OBSERVATIONAL COHORT STUDY.

OBJECTIVE: The aim: To find out whether diaphragm dysfunction might lead to unsuccessful weaning from MV. PATIENTS AND METHODS: Materials and methods: We provided prospective observational cohort study and included 105 patients and divided them in the study and the control groups. To consider diaphragm function, we check amplitude of its movement and diaphragm thickening fraction (Dtf). The primary outcome was the incidence of successful weaning from MV. The secondary outcomes were changes in diaphragm function parameters. RESULTS: Results: In the current study, there were found that the incidence of successful weaning from MV was 100% for the day 1 in the control group, while in study group the incidence was significantly lower. Successfully weaned from MV in the study group among children 1 month - 1 year old on day 14 were 20 out 28 patients (71%), in children 1 - 3 years old - 9 out 11 patients (82%), in children 3 - 5 years old - 15 out 15 (100%). However, on day 1 - no one from the study group was weaned (0%), on day 7 - 5 out 28 patients 1 month - 1 year old (18%), 6 out 11 patients (55%) 1 - 3 years old, and 8 out 15 patients (53%) 3 - 5 years old (p<0.05). CONCLUSION: Conclusions: Diaphragm dysfunction might alter weaning from MV.

Quantification of cardiac and respiratory modulation of axonal activity in the human vagus nerve.

We recently documented the first microelectrode recordings from the cervical vagus nerve in awake humans. Here we aimed to quantify cardiac and respiratory modulation of vagal activity to assess the feasibility of targeting axons supplying the heart and airways. Multi-unit activity was recorded from 43 sites in 19 healthy participants in the left (n = 10) and right (n = 9) vagus nerves with ECG, continuous non-invasive blood pressure and respiration. Cross-correlation histograms were constructed between axonal spikes and the R-waves or the peaks of inspiration. The latencies for the peak in cardiac modulation showed a bimodal distribution: while the majority of sites (72%) had peak latencies that preceded the R-wave by up to 550 ms (mean ± SD, -300 ± 178 ms), 12 sites had latencies of up to 250 ms following the R-wave (64 ± 87 ms). Interestingly, the majority of sites with negative latencies (68%) were found in the left nerve whereas most of those with positive latencies (75%) were found in the right. Conversely, on average the peak of respiratory modulation straddled the peak of inspiration. Sites showing respiratory modulation were more prevalent and showed stronger modulation than those with cardiac modulation: calculated for sites with modulation indices ≥15%, the median cardiac and respiratory modulation indices were 23.4% (n = 17) and 44.5% (n = 35), respectively. We conclude that, despite the fact that much of the vagus nerve supplies the gut, cardiac and respiratory modulation of vagal nerve activity can be identified through invasive recordings in awake humans. KEY POINTS: Intraneural recordings from the cervical vagus were obtained in awake humans via tungsten microelectrodes inserted into the nerve through ultrasound guidance. Cross-correlation analysis of multi-unit vagal activity revealed cardiac and respiratory modulation, from which the amplitude and latency of the peaks could be computed. The magnitude of the cardiac modulation (23%) was weaker than that of the respiratory modulation (45%). The latencies for the peak in cardiac modulation showed a bimodal distribution: the majority of sites (72%) had peak latencies that preceded the R-wave, while the remainder had latencies that followed the R-wave. The majority of sites with negative latencies (68%) were found in the left nerve whereas most of those with positive latencies (75%) were found in the right. On average the peak of respiratory modulation coincided with the peak of inspiration.

Sensitive physiological readouts to evaluate countermeasures for lipopolysaccharide-induced lung alterations in mice.

Despite decades of research, studies investigating the physiological alterations caused by an acute bout of inflammation induced by exposing the lung to lipopolysaccharide have yielded inconsistent results. This can be attributed to small effects and/or a lack of fitted physiological testing. Herein, a comprehensive investigation of lung mechanics was conducted on 270 male C57BL/6 mice at 24, 48, or 96 h after an intranasal exposure to saline or lipopolysaccharide at either 1 or 3 mg/kg (30 mice per group). Traditional techniques that probe the lung using small-amplitude perturbations (i.e., oscillometry) were used, together with less conventional and new techniques that probe the lung using maneuvers of large amplitudes. The latter include a partial and a full-range pressure-volume maneuvers to measure quasi-static elastance, compliance, total lung volume, vital capacity, and residual volume. The results demonstrate that lung mechanics assessed by oscillometry was only slightly affected by lipopolysaccharide, confirming previous findings. In contradistinction, lipopolysaccharide markedly altered mechanics when the lung was probed with maneuvers of large amplitudes. With the dose of 3 mg/kg at the peak of inflammation (48 h postexposure), lipopolysaccharide increased quasi-static elastance by 26.7% (P < 0.0001) and decreased compliance by 34.5% (P < 0.0001). It also decreased lung volumes, including total lung capacity, vital capacity, and residual volume by 33.3%, 30.5%, and 43.3%, respectively (all P < 0.0001). These newly reported physiological alterations represent sensitive outcomes to efficiently evaluate countermeasures (e.g., drugs) in the context of several lung diseases.

Cerebrospinal fluid and arterial acid-base equilibria in spontaneously breathing third-trimester pregnant women.

BACKGROUND: Acid-base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. METHODS: We enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide ( [Formula: see text] ), and pH were measured in simultaneously collected CSF and arterial blood samples. RESULTS: All pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial [Formula: see text] <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (-7.8 [1.4] vs -11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. CONCLUSIONS: Primary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid-base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment. CLINICAL TRIAL REGISTRATION: NCT03496311.

The role of impulse oscillometry in the management of asthma when forced expiratory maneuvers are contraindicated: case series and literature review.

Objectives: The impulse oscillometry system (IOS) provides an alternative method of lung function testing for patients in whom forced expiratory manoeuvres are contraindicated, such as those with inherited vascular connective tissue disorders. Here we examine the role of IOS in the diagnosis and monitoring of asthma in such patients through a clinical case series and literature review.Methods: The clinical case series comprised of data from 12 patients with inherited connective tissue disorders representing 32 clinical encounters. Of these, 11 encounters were for asthma diagnosis and 21 were for asthma monitoring. Symptoms, exhaled nitric oxide (FeNO) and IOS were assessed at each encounter.Results: In the clinical case series, 5 of 6 patients with likely asthma (as determined by physician review and exhaled nitric oxide testing) had abnormal IOS parameters compared with 0 of 5 of those with unlikely asthma. In the monitoring group, 11 encounters resulted in treatment escalation (demonstrating suboptimal control), and 8 resulted in no change to treatment (good control). Six of 11 of those with suboptimal control had abnormalities in ≥3 IOS parameters, with R5 and R5-20 most frequently affected. Only 1 of 8 of those with good control had abnormalities in ≥3 IOS parameters.Conclusions: IOS can be used as an alternative to conventional lung function testing to support the diagnosis and monitoring of asthma when forced expiratory manoeuvres are contraindicated. Larger studies are required to establish severity and treatment escalation thresholds and provide clearer comparisons with spirometry values.

The (human) respiratory rate at rest.

All schoolchildren know how often they breathe, but even experts don't know exactly why. The aim of this publication is to develop a model of the resting spontaneous breathing rate using physiological, physical and mathematical methods with the aid of the principle that evolution pushes physiology in a direction that is as economical as possible. The respiratory rate then follows from an equation with the parameters [Formula: see text]-production rate of the organism, resistance, static compliance and dead space of the lungs, the inspiration duration: expiration duration - ratio and the end-expiratory [Formula: see text] fraction. The derivation requires exclusively secondary school mathematics. Using the example of an adult human or a newborn child, data from the literature then result in normal values for their breathing rate at rest. The reason for the higher respiratory rate of a newborn human compared to an adult is the relatively high [Formula: see text]-production rate together with the comparatively low compliance of the lungs. A side result is the fact that the common alveolar pressure throughout the lungs and the common time constant is a consequence of the economical principle as well. Since the above parameters are not human-specific, there is no reason to assume that the above equation could not also be applicable to many animals breathing through lungs within a thorax, especially mammals. Not only physiology and biology, but also medicine, could benefit: Applicability is being discussed in pulmonary function diagnostics, including pathophysiology. However, the present publication only claims to be a theoretical concept of the spontaneous quiet breathing rate. In the absence of comparable animal data, this publication is intended to encourage further scientific tests.

Non-invasive Ventilation: Effect of Vented and Non-vented Exhalation Systems on Inspiratory CO2 and O2 Concentrations, Ventilation, and Breathing Pattern.

INTRODUCTION: To increase CO2 elimination and to reduce work of breathing in hypercapnic patients, non-invasive ventilation (NIV) can be applied via mask either with non-vented CO2 exhalation systems or with vented systems with leak port. The effect of the exhalation system on CO2 rebreathing in the mask and total gas exchange remains widely unknown. Aim of this study was to compare the exhalation systems in terms of inspiratory O2 and CO2 concentrations, breathing patterns and gas exchange. METHODS: We prospectively examined 10 healthy subjects and 10 hypercapnic patients with both exhalation systems. O2 and CO2 were measured in the nose, in the mask, and in the ventilation circuit, and respiratory rate, tidal volume, and transcutaneous capnometry (PtcCO2) were recorded during the experiments. RESULTS: Using the non-vented system, CO2 concentrations in the mask were significantly higher in both subject groups, and PtcCO2 values in the patient group increased up to 3.6 mmHg compared to the vented system (p = 0.011). O2 concentrations increased with higher O2 flow rates, but were significantly lower in the vented settings in both groups. No effect in breathing pattern could be demonstrated during the measurement time. CONCLUSION: Using NIV, the chosen exhalation system influences CO2 and O2 concentrations under the mask, CO2 rebreathing from the mask and could influence the effectiveness of the ventilation support with regards to hypercapnia treatment. To compensate for relevant hypoxia, the O2 supplementation must be set up to a sufficient level under a vented system.