Plethysmographic Measurements Research Articles

Adapting Real-Time Lung Function Measurements for SARS-CoV-2 Infection Studies in Syrian Hamsters.

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed.

Ethanol pre-exposure attenuates the hypoxic ventilatory response and may attenuate expression of long term facilitation following intermittent hypoxia treatment in adult rats

Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in which airway collapse or obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures during sleep can induce intermittent hypoxemia, sympathetic activation, and sleep fragmentation which can lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia, which consists of alternating exposure to hypoxia and normal oxygen levels (normoxia), can induce a long-lasting increase in breathing motor output called long term facilitation (LTF) and is currently being investigated as a therapeutic treatment. Interestingly, experts in the field of LTF have noted how IH models some key aspects of OSA. It has been well established through clinical studies that ethanol consumption prior to sleep exacerbates existing OSA, increasing the apnea/hypopnea index and worsening arterial blood oxygen desaturations during the night. However, it is unknown whether ethanol affects expression of LTF following IH treatment. If LTF might serve as a means of increasing ventilatory output to compensate for periods of apnea and hypopnea during OSA, ethanol might not only worsen the severity of OSA, but impede individuals’ compensatory response. Thus, for this study we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the hypoxic ventilatory response during IH treatment. Using adult female Sprague-Dawley rats, we administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol through intraperitoneal injection to model a 2-drink nightcap or binge drinking-type ethanol exposure, respectively. Immediately afterwards, we measured subjects’ ventilatory output during baseline, then during a 5 by 3-minute moderate IH protocol, and for one hour following the end of IH using whole-body plethysmography. Finally, we took venous blood samples to assay serum ethanol concentration at the end of the approximately 2.5 hour plethysmography measurement. Results from the high-dose ethanol group indicate that ethanol pre-exposure might attenuate respiratory rate and minute volume LTF in comparison to saline-treated control. Furthermore, high-dose ethanol attenuated the hypoxic ventilatory response with respect to respiratory rate and minute volume. Low dosage of ethanol attenuated subjects’ HVR of respiratory rate and minute volume, but conflictingly trends towards increasing LTF of tidal volume while diminishing LTF of respiratory rate when compared to saline control. Overall, our findings indicate that high levels of ethanol exposure dramatically diminish the acute ventilatory response to hypoxic exposure and may impede long-term increases in ventilatory output following IH treatment. On the other hand, lower doses of ethanol have a subtler effect on the ventilatory response to hypoxia. Future directions will include analysis of additional parameters of ventilatory function to gain a more detailed understanding of how ethanol effects respiratory plasticity in the context of intermittent hypoxic exposure. NIH 5T32 AA027488 to ALSUniversity of Kentucky Endowment to WJA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague-Dawley Rats.

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5'-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5'-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.

Relationship Between Lung Volumes and Heterogeneity in the Response to Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease

The effects of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory outcomes for people with cystic fibrosis (CF) were demonstrated by several clinical trials, mainly based on simple spirometry. However, gains in lung function may vary greatly between patients, and predictors of FEV1 change after treatment have yet to be defined. Which ventilatory parameters are involved in the heterogeneity of FEV1 change after 12-month ETI treatment in people with CF and advanced lung disease? This was a multicenter, observational, prospective cohort study at two major CF centers in Italy. We enrolled 47 adults with CF and advanced lung disease (FEV1< 40%or actively listed for lung transplant) who started ETI treatment between December 2019 and December 2021. At treatment initiation and after 12months, patients underwent body plethysmography. Values were compared at the two time points. To assess the relationship between baseline plethysmography measurements and treatment-induced changes in FEV1, we used the Spearman rank correlation coefficient (rs) and median quantile regressions. After 12months of ETI treatment, there was a significant increase in FEV1 %predicted from a median value of 36.0 (25th-75th percentile, 33-39) to 52 (25th-75th percentile, 43-61) (P< .001). Inspiratory capacity/total lung capacity (TLC) ratio also increased from 32.0 (25th-75th percentile, 28.6-36.9) to 36.3 (25th-75th percentile, 33.4-41.3) (P< .001). Specific airway resistance decreased from 263 (25th-75th percentile, 182-405) to 207 (25th-75th percentile, 120-258) (P< .001). Functional residual capacity/TLC ratio decreased from 68.2 (25th-75th percentile, 63.3-71.9) to 63.9 (25th-75th percentile, 58.8-67.1) (P< .001), and residual volume/TLC ratio decreased from 53.1 (25th-75th percentile, 48.3-59.4) to 45.6 (25th-75th percentile, 39.4-49.8) (P< .001). Changes in FEV1 %predicted negatively correlated with baseline functional residual capacity/TLC ratio (rs=-0.38, P= .009) and residual volume/TLC ratio (rs =-0.42, P= .004). After adjustment for age at treatment initiation and cystic fibrosis transmembrane conductance regulator genotype, we estimated that for each 10-unit increase in baseline residual volume/TLC ratio, the expected median change in FEV1 decreased by 2.3 (95%CI,-5.8 to-0.8). ETI was associated with improvements in both static and dynamic volumes in people with CF and advanced lung disease. Heterogeneity in FEV1 %predicted change after 12months of treatment may be predicted by the severity of hyperinflation at baseline.

Residual reversibility in COPD patients already on long-acting bronchodilator: The OscilloRevers Study

BackgroundDyspnea is a complex symptom of chronic obstructive pulmonary disease (COPD) which is not strongly correlated with lung function measures. Long-acting bronchodilators (LAB) may reduce this dyspnea, but some patients report persistent chronic dyspnea despite this treatment. This study aims to assess residual reversibility and clinical response after short-acting bronchodilator (SAB) in COPD patients already treated by LAB and reporting persistent dyspnea. MethodsCOPD patients with a persistent dyspnea (modified Medical Research Council scale (mMRC) ≥1) despite current stable treatment with at least one LAB were included. Spirometry, plethysmography and impulse oscillometry (IOS) were performed at peak effect of their LAB and repeat 45 min after the intake of two SAB (400 µg of salbutamol and 80 µg of ipratropium). Dyspnea improvement was assessed at 45 min after SAB through a comparative two-sided VAS (-100 mm for maximal improvement; +100 mm for maximal degradation). ResultsTwenty-two COPD patients were analyzed, mainly men (59.1 %) with a mean age of 60.6 years and a median FEV1 of 54 % of predicted values. Fifty percent of patients reported a severe basal dyspnea (mMRC ≥2). After SAB, spirometric and plethysmographic measurements were statistically improved. For IOS measurement, reactance at 5 Hz (X5) and area of reactance (AX) were also improved. Fifty percent of patients reported a clinically relevant improvement of their resting dyspnea. However, no correlation was found between dyspnea improvement and functional measures. ConclusionsFifty percent of COPD patients regularly treated with one or two LAB still report a relevant improvement of resting dyspnea after the adjunctive intake of double short-acting bronchodilators. Physiological mechanisms associated with this improvement remain to be determined. Clinical Trial RegistrationNCT02928744

The Impact of Stretching Intensities on Neural and Autonomic Responses: Implications for Relaxation.

Stretching is an effective exercise for increasing body flexibility and pain relief. This study investigates the relationship between stretching intensity and relaxation effects, focusing on brainwaves and autonomic nervous system (ANS) activity. We used a crossover design with low- and high-intensity conditions to elucidate the impact of varying stretching intensities on neural activity associated with relaxation in 19 healthy young adults. Participants completed mood questionnaires. Electroencephalography (EEG) and plethysmography measurements were also obtained before, during, and after stretching sessions. The hamstring muscle was targeted for stretching, with intensity conditions based on the Point of Discomfort. Data analysis included wavelet analysis for EEG, plethysmography data, and repeated-measures ANOVA to differentiate mood, ANS activity, and brain activity related to stretching intensity. Results demonstrated no significant differences between ANS and brain activity based on stretching intensity. However, sympathetic nervous activity showed higher activity during the rest phases than in the stretch phases. Regarding brain activity, alpha and beta waves showed higher activity during the rest phases than in the stretch phases. A negative correlation between alpha waves and sympathetic nervous activities was observed in high-intensity conditions. However, a positive correlation between beta waves and parasympathetic nervous activities was found in low-intensity conditions. Our findings suggest that stretching can induce interactions between the ANS and brain activity.

Strain-gauge venous occlusion plethysmography: An objective and non-invasive approach to the evaluation of venous hemodynamics in patients with acute deep-vein thrombosis undergoing post-pharmacomechanical thrombolysis.

Strain-gauge venous occlusion plethysmography (SGVOP) is a means of acquiring hemodynamic data non-invasively, unlike other methods used routinely for the diagnosis and follow-up of venous diseases. The present study compares the plethysmographic data with early- and mid-term routine data of patients with acute deep-vein thrombosis (DVT) who underwent pharmacomechanical thrombolysis. Included in this retrospective study were 118 patients with acute DVT, who underwent pharmacomechanical thrombolysis between February 2018 and July 2019. Pre- and post-procedure follow-up data including CIVIQ-20 (quality of life), VCSS (Venous Clinical Severity Score), D-Dimer, Doppler USG results, venous capacity (VC), and venous outflow (VO) obtained by SGVOP were recorded and compared. In all 118 (100%) patients who underwent the procedure, early- and mid-term patency was seen to have been provided on Doppler USG follow-up, and various degrees of venous insufficiency were identified. A statistically significant improvement was observed in VCSS, CIVIQ-20, D-Dimer, VO, and VC measurements, although when the discrepancies between CIVIQ-20 and plethysmographic measurements were examined individually during the 6-month follow-up, nine (13.1%) patients were identified with comorbidities. Pharmacomechanical thrombolysis is an effective treatment approach for patients with acute DVT. Providing non-invasive objective data supporting the diagnosis and follow-up of venous diseases, the SGVOP approach offers significant benefits and should be considered more frequently as a viable therapy.

Novel noninvasive indices of perfusion dynamics wave analysis detect above knee arterial stenosis in the presence of widespread arteriosclerosis

Abstract Introduction Peripheral arterial disease (PAD) is a leading cause of vascular morbidity and mortality. The Ankle Brachial Index (ABI) is a common index for screening and monitoring PAD. The AHA and ECS guidelines recommend measuring the ABI for assessing atherosclerotic cardiovascular risk. However, the ABI sensitivity is low, especially in the elderly and diabetics with arteriosclerosis. The restenosis rate after revascularization is high and there is an unmet need for continuous monitoring for detection of restenoses in these patients. ABI requires Doppler Ultrasound measurements. Purpose We hypothesized that monitoring the arterial perfusion dynamics instead of the peak systolic pressure, could improve PAD surveillance and management. Methods A novel method for quantifying the arterial perfusion dynamic from impedance plethysmography measurements was developed. A novel segmentation of the arterial perfusion upstroke has revealed that it consists of two characteristic phases, an initial slow phase that is followed by a fast vigorous rise. The phase transition point was defined by the maximum acceleration time point (MAT). The slow phase duration was denoted as the `Perfusion Deficit Index` (PDI). The arterial perfusion signals were derived from calves of PAD patients that were admitted for revascularization. We compared the novel PDI and MAT indices with measured ABI before and after the revascularizations. Results Sixteen patients with isolated above-knee stenoses were recruited and treated in eighteen legs. The perfusion signals before the revascularization were characterized by prolonged PDI, and overt shortening of the PDI was observed after successful revascularization, as depicted in Figure 1. The PDI was significantly negatively correlated with the ABI. In patients with satisfactory postoperative increase in ABI (&amp;gt;0.15) the PDI dropped from 105±33 ms to 26±16 ms (n=13, p&amp;lt;0.001). The “pulse transit time” (PTT) that relates to arteriosclerosis did not change between measurements in all the patients. Thus, the measurement of the PTT and PDI can differentiate between the two elements of atherosclerosis: generalized arteriosclerosis and development of localized arterial narrowing. Interestingly, in the contralateral untreated leg the ABI and PDI had a similar significantly negative correlation, without significant difference before and after the procedures. Assessment of the ABI and PDI abilities to detect focal stenosis revealed that the PDI detected stenosis with 91% sensitivity and 85% specificity, while the ABI only had 74% sensitivity and 85% specificity (Figure 2). Conclusions The PD can be used for assessing revascularization outcome and monitoring atherosclerosis severity. The MAT and PDI are novel sensitive and specific indices for detecting arterial stenoses, even in the presence of arteriosclerosis, unlike the ABI. The applicability of this simple to use method for screening and telemedicine should be further validated. Funding Acknowledgement Type of funding sources: None.

Maximal Calf Vasodilation Influences 6-Minute Walk Distance In PAD And Non-PAD Groups

PURPOSE: To (1) compare the maximal calf vascular conductance and 6-minute walk distance (6MWD) of participants with and without symptomatic peripheral artery disease (PAD), and (2) determine whether maximal calf vascular conductance was associated with 6MWD in both groups before and after adjusting for ankle-brachial index (ABI), and for demographic, anthropometric, and co-morbid characteristics. METHODS: Participants with (n = 633, 67.7 + 8.4 yr) and without (n = 327, 63.9 ± 10.4 yr) PAD underwent ambulatory function testing including 6MWD, resting ABI, and plethysmographic measurements of calf blood flow and vascular conductance at rest and during maximal hyperemia (ischemic toe raises to fatigue). Participants were further characterized on demographic, anthropometric, and co-morbid (age, hypertension, diabetes, smoking, etc) variables. RESULTS: The PAD group had lower maximal calf conductance (135.8 ± 71.4 vs. 200.7 ± 112.7 % reperfusion/min/mmHg, p < 0.001) and shorter 6MWD (375 ± 98 vs. 480 ± 107 meters, p < 0.001) than the non-PAD group (means+SD). Maximal calf conductance was positively associated with 6MWD in the PAD group (p < 0.001) and in the non-PAD group (p < 0.001). These positive associations remained significant after adjusting for disease severity (ABI) and co-morbid conditions in the PAD group (p < 0.001), and after adjusting for age and co-morbid conditions in the non-PAD group (p < 0.001). Calf circumference was also a significant independent predictor of 6MWD in both groups (p < 0.001) CONCLUSIONS: Maximal calf vascular conductance, an index of microvascular function, is important in explaining variance in 6MWD in PAD and non-PAD groups, even after controlling for ABI and the influences of co-morbid conditions.

Pulmonary MRI and Cluster Analysis Help Identify Novel Asthma Phenotypes.

Outside eosinophilia, current clinical asthma phenotypes do not show strong relationships with disease pathogenesis or treatment responses. While chest x-ray computed tomography (CT) phenotypes have previously been explored, functional MRI measurements provide complementary phenotypic information. To derive novel data-driven asthma phenotypic clusters using functional MRI airway biomarkers that better describe airway pathologies in patients. Retrospective. A total of 45 patients with asthma who underwent post-bronchodilator 129 Xe MRI, volume-matched CT, spirometry and plethysmography within a 90-minute visit. Three-dimensional gradient-recalled echo 129 Xe ventilation sequence at 3T. We measured MRI ventilation defect percent (VDP), CT airway wall-area percent (WA%), wall-thickness (WT, WT* [*normalized for age/sex/height]), lumen-area (LA), lumen-diameter (D, D*) and total airway count (TAC). Univariate relationships were utilized to select variables for k-means cluster analysis and phenotypic subgroup generation. Spirometry and plethysmography measurements were compared across imaging-based clusters. Spearman correlation (ρ), one-way analysis of variance (ANOVA) or Kruskal-Wallis tests with post hoc Bonferroni correction for multiple comparisons, significance level 0.05. Based on limited common variance (Kaiser-Meyer-Olkin-measure=0.44), four unique clusters were generated using MRI VDP, TAC, WT* and D* (52 ± 14 years, 27 female). Imaging measurements were significantly different across clusters as was the forced expiratory volume in 1-second (FEV1 %pred ), residual volume/total lung capacity and airways resistance. Asthma-control (P=0.9), quality-of-life scores (P=0.7) and the proportions of severe-asthma (P=0.4) were not significantly different. Cluster1 (n=15/8 female) reflected mildly abnormal CT airway measurements and FEV1 with moderately abnormal VDP. Cluster2 (n=12/12 female) reflected moderately abnormal TAC, WT and FEV1 . In Cluster3 and Cluster4 (n=14/6 female, n=4/1 female, respectively), there was severely reduced TAC, D and FEV1 , but Cluster4 also had significantly worse, severely abnormal VDP (7 ± 5% vs. 41 ± 12%). We generated four proof-of-concept MRI-derived clusters of asthma with distinct structure-function pathologies. Cluster analysis of asthma using 129 Xe MRI in combination with CT biomarkers is feasible and may challenge currently used paradigms for asthma phenotyping and treatment decisions. 3 TECHNICAL EFFICACY: Stage.

Airway diameter at different transpulmonary pressures in ex vivo sheep lungs: implications for deep inspiration-induced bronchodilation and bronchoprotection

Deep inspiration (DI)-induced bronchodilation is the first line of defense against bronchoconstriction in healthy subjects. A hallmark of asthma is the lack of this beneficial effect of DI. The mechanism underlying the bronchodilatory effect of DI is not clear. Understanding the mechanism will help us unravel the mystery of asthma pathophysiology. It has been postulated that straining airway smooth muscle (ASM) during a DI could lead to bronchodilation and bronchoprotection. The hypothesis is currently under debate, and a central question is whether ASM is sufficiently stretched during a DI for its contractility to be compromised. Besides bronchoconstriction, another contributor to lung resistance is airway heterogeneity. The present study examines changes in airway diameter and heterogeneity at different lung volumes. Freshly explanted sheep lungs were used in plethysmographic measurements of lung resistance and elastance at different lung volumes, whereas the airway dimensions were measured by computed tomography (CT). The change in airway diameter informed by CT measurements was applied to isolated airway ring preparations to determine the strain-induced loss of ASM contractility. We found that changing the transpulmonary pressure from 5 to 30 cmH2O led to a 51% increase in lung volume, accompanied by a 46% increase in the airway diameter with no change in airway heterogeneity. When comparable airway strains measured in the whole lung were applied to isolated airway rings in either relaxed or contracted state, a significant loss of ASM contractility was observed, suggesting that DI-induced bronchodilation and bronchoprotection can result from strain-induced loss of ASM contractility.

Efficacy of Nebulized Glycopyrrolate on Lung Hyperinflation in Patients with COPD.

IntroductionLung hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with activity limitation, impaired cardiac output, and mortality. Several studies have demonstrated that long-acting muscarinic antagonists (LAMAs) delivered by dry powder inhalers can promote lung deflation; however, the potential of nebulized LAMAs on improving hyperinflation in COPD is currently unknown.MethodsThis single-center, randomized, double-blind, two-way crossover study (NCT04155047) evaluated the efficacy of a single dose of nebulized LAMA [glycopyrrolate (GLY) 25 µg] versus placebo in patients with COPD and lung hyperinflation. Patients with moderate-to-severe COPD and a residual volume (RV) ≥ 130% of predicted normal were included. The primary endpoint was changed from baseline in RV at 6 h post-treatment. Other endpoints included changes from baseline in spirometric and plethysmographic measures up to 6 h post-treatment.ResultsA total of 22 patients (mean pre-bronchodilator RV, 153.7% of predicted normal) were included. The primary objective of the study was not met; the placebo-adjusted least squares (LS) mean [95% confidence interval (CI) change from baseline in RV with GLY at 6 h post-treatment was − 0.323 l (− 0.711 to 0.066); p = 0.0987]. A post hoc evaluation of the primary analysis was conducted after excluding a single statistical outlier; substantial improvements in RV with GLY compared with placebo was observed after exclusion of this outlier [placebo-adjusted LS mean change from baseline (95% CI) in RV was − 0.446 l (− 0.741 to − 0.150)]. Improvements from baseline were also observed with GLY compared with placebo in spirometric and plethysmographic measures up to 6 h post-treatment. GLY was generally safe, and no new safety signals were detected.ConclusionsThis is the first study to evaluate the effect of nebulized GLY on lung deflation. Nebulized GLY resulted in marked improvements in RV up to 6 h post-treatment, compared with placebo. Improvements were also observed with GLY in spirometric and plethysmographic parameters of lung function.Trial RegistrationClinicalTrials.gov identifier, NCT04155047.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00166-5.

Assessment of respiratory effort with EMG extracted from ECG recordings during prolonged breath holds: Insights into obstructive apnea and extreme physiology.

Breath holding divers display extraordinary voluntary control over involuntary reactions during apneic episodes. After an initial easy phase to the breath hold, this voluntary control is applied against the increasing involuntary effort to inspire. We quantified an electromyographic (EMG) signal associated with respiratory movements derived from broad bandpass ECG recordings taken from experienced breath holding divers during prolonged dry breath holds. We sought to define their relationship to involuntary respiratory movements and compare these signals with what is known to occur in obstructive sleep apnea (OSA) and epileptic seizures. ECG and inductance plethysmography records from 14 competitive apneists (1 female) were analyzed. ECG records were analyzed for intervals and the EMG signal was extracted from a re‐filtered version of the original broad bandpass signal and ultimately enveloped with a Hilbert transform. EMG burst magnitude, quantified as an area measure, increased over the course of the struggle phase, correlated with inductance plethysmography measures, and corresponded to significant variance in heart rate variability. We conclude that an EMG signal extracted from the ECG can complement plethysmography during breath holds and may help quantify involuntary effort, as reported previously for obstructive sleep apnea. Further, given the resemblance between cardiac and respiratory features of the breath hold struggle phase to obstructive apnea that can occur during sleep or in association with epileptic seizure activity, the struggle phase may be a useful simulation of obstructive apnea for controlled experimentation that can help clarify aspects of acute and chronic apnea‐associated physiology.

Abnormal preoperative digital brachial index is associated with lower 2-year arteriovenous fistula access patency

ObjectiveThe aim of the present study was to assess whether a single measurement of the digital brachial index (DBI; systolic finger pressure/systemic pressure ratio), reflecting the arm's circulation, was associated with access patency in patients with severe chronic kidney disease scheduled for arteriovenous fistula (AVF) creation. MethodsA bilateral DBI was obtained using digital plethysmography just before construction of the patient's first AVF from January 2009 to December 2017 at one center. A DBI of 80% to 99% was considered normal, and a DBI of <80% (low) or DBI of ≥100% (high) were considered abnormal. DBI values ipsilateral to the AVF were used for analysis. The primary and secondary access patency rates were calculated using reported standards and compared using standard statistical techniques. ResultsData sets of 163 patients were obtained (69 women; age, 71 ± 12 years). The median follow-up was 40 weeks (range, 0-104 weeks; follow-up index, 99% ± 1%). Patients with abnormal preoperative DBI values had lower 2-year primary patency rates (low DBI, 25% ± 11%; high DBI, 28% ± 6%; normal DBI, 49% ± 8%; P = .018). After correction for age, sex, hypertension, diabetes mellitus, cardiovascular disease, smoking status, and a history of ipsilateral central venous catheter use, an adjusted model demonstrated that abnormal DBI values conferred an increased risk of primary patency failure (low DBI [<80%]: hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.13-4.48; high DBI [≥100%]: HR, 1.74; 95% CI, 1.06-2.85; P < .030 for both). Patients with a low preoperative DBI had also had diminished secondary patency (HR, 2.86; 95% CI, 1.08-7.59; P = .035). In contrast, the diameters of the outflow veins did not determine access patency. ConclusionsPatients with abnormal DBI values before AVF construction for hemodialysis had lower 2-year access patency rates compared with patients with a normal DBI. Plethysmographic finger measurements might have a role in the preoperative counseling of patients with severe chronic kidney disease requiring an AVF.

Original Article: Clinical Research.

Aim:In this study, we aimed to investigate the possible role of endotrophin, a profibrotic byproduct of collagen VI, in the complex process of fibrosis development in the disease group with pulmonary fibrosis among interstitial lung diseases.Material and Method:When the patients’ participation in the study were completed, smoking or alcohol drinking conditions, and family history were recorded. Their weights and heights were recorded and body mass index (BMI) was calculated. In every patient, Spirometry with bronchodilator testing, determination of single-breath DLCO, and plethysmographic measurement of thoracic gas volume and airway resistance were performed. Blood samples were obtained for the inflammation markers such as sedimentation rate, C-reactive protein (CRP), complete blood count, liver and renal function tests, and lactate dehydrogenase levels. Serum endotrophin levels were measured in all patients.Results:Thirty-five patients with interstitial lung disease who were having pulmonary fibrosis, 35 patients with interstitial lung disease without pulmonary fibrosis, and 20 control patients without any signs or symptoms of interstitial lung disease were included in the study. Age distribution was similar between groups. The fibrotic ILD group was more commonly smoker or ex-smoker compared with the non-fibrotic ILD patients or control cases. Fibrotic ILD patients were leaner, having significantly decreased total lung capacity, diffusion capacity, and higher LDH levels. In the comparison of the 3 study groups regarding the endotrophin levels, there was a significant difference between groups. The fibrotic and non-fibrotic patient groups were compared for the Endotrophin levels and the difference was also significant. However, there was not any significant difference regarding the endotrophin levels between control cases and non-fibrotic ILD patients. Smoked cigarette pocket x year showed a significant positive correlation and DLCO % and KCO % showed a significant negative correlation with the endotrophin levels.Conclusion:Serum endotrophin levels significantly increase in fibrotic ILD patients compared with the non-fibrotic ILD patients and control cases. Endotrophin may be suggested as a diagnostic marker in fibrotic interstitial lung diseases.

Peripheral obstruction without airflow limitation is rare and not specific to asthma in children.

Peripheral (or small) airway obstruction (PAO) is considered a marker of childhood asthma but the techniques able to directly measure it are rarely used in routine. Usual spirometry and plethysmography can detect a certain degree of PAO when reduced forced vital capacity (FVC) is associated to normal forced expiratory volume in 1 s (FEV1 ) to FVC ratio, and normal total lung capacity (TLC). The frequency of this functional pattern has never been studied in different pediatric respiratory conditions. To assess the prevalence and outcome of PAO in children with different diseases or symptoms, we retrospectively extracted from our database all files of Caucasian subjects encompassing spirometry and plethysmography measurements. Spirometry patterns (normal, airflow limitation [AFL; low FEV1 /FVC], low FVC [with normal FEV1 /FVC]) and final functional patterns (normal, AFL, PAO, restrictive [low TLC], or mixed) were described. We included 4394 files recorded in 1794 children (median [IQR] age: 10.7 [9.2-12.9] years). At inclusion, 125 (7%) children had low FVC of which 56 (44.8%, and 3.1% [95% CI 2.3-3.9] of the whole population) had PAO. PAO prevalence increased with age (OR (95% CI) per 2-year-increase: 2.26 (1.59-3.23); p < .001), and was more frequent in chronic bronchial diseases other than asthma (1.6% vs. 8.0%). On repeated tests, PAO frequently normalized (26.1%) or persisted (43.5%), but it less often progressed into AFL (13%) or restrictive (13%) patterns. PAO is an infrequent nonspecific and persistent functional pattern. Its prevalence increases with age and in diagnosis of chronic respiratory diseases other than asthma.

SHORT-TERM PULMONARY FUNCTION TEST CHARACTERISTICS IN PATIENTS DIAGNOSED WITH E-CIGARETTE- OR VAPING-ASSOCIATED LUNG INJURY

SESSION TITLE: Tobacco Cessation and Prevention Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The E-cigarette, or vaping, associated lung injury (EVALI) outbreak in 2019 caused many young people to be hospitalized with severe lung disease. What, if any, residual pulmonary abnormalities assessed by pulmonary function tests (PFTs) remain at short term follow-up in patients with EVALI is unknown. METHODS: We studied all patients who presented with EVALI at Intermountain Healthcare facilities between June 1, 2019 and January 13, 2020. We reviewed PFTs on all patients who were at least 30 days post discharge. We included PFTs with spirometry, lung volume, and/or diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin and reported patterns of abnormalities for all abnormal PFTs. RESULTS: 114 patients presented with EVALI and 111 were alive at least 30 days post-discharge. 28% (31/111) had at least one PFT performed at a median of 36 days (IQR 17 – 53) post-discharge. 52% (16/31) of patients with PFTs performed had abnormal PFTs. 2 of the 16 patients (13%) with abnormal PFTs at follow-up had abnormal PFTs at baseline. 65% (20/31) of patients had PFTs performed with spirometry, single-breath total lung capacity testing, and DLCO testing. 19% (6/31) had PFTs with spirometry, total lung capacity testing with plethysmography, and DLCO testing. 16% (5/31) had PFTs with spirometry only. There were six patterns of abnormalities. 19% (6/31) had obstruction only, 16% (5/31) had DLCO reduction only with normal spirometry, 6% (2/31) had obstruction with DLCO reduction. 3% (1/31) had restriction and DLCO reduction, 3% (1/31) had obstruction and suggested restriction, and 3% (1/31) had DLCO reduction and suggested restriction. The patients with suggested restriction had a low forced expiratory volume in one second (FEV1) and low forced vital capacity (FVC) without TLC plethysmography measurement. 44% of patients with abnormal PFTs (7/16) had a second, follow up PFT at a median of 135 days (IQR 79 - 145) post-discharge. None of these 7 patients had baseline PFTs prior to their EVALI diagnosis. 43% (3/7) of these follow up PFTs improved to normal, the other 4 had residual abnormalities. CONCLUSIONS: Many patients with EVALI had abnormal PFTs at least 30 days post-discharge with the most common abnormalities being obstruction only, DLCO reduction only, and obstruction with DLCO reduction. Patients who had PFT abnormalities continued to improve (some to normal predicted values) with subsequent testing. CLINICAL IMPLICATIONS: Many patients diagnosed with EVALI have persistent PFT abnormalities at follow up. Further study of the long-term effects of EVALI on pulmonary function is needed. DISCLOSURES: No relevant relationships by Braden Anderson, source=Web Response No relevant relationships by Denitza Blagev, source=Web Response No relevant relationships by Colin Grissom, source=Web Response No relevant relationships by David Guidry, source=Web Response No relevant relationships by Dixie Harris, source=Web Response No relevant relationships by Michael Lanspa, source=Web Response No relevant relationships by Susan Rea, source=Web Response

Measurement of aortofemoral volume wave velocity during the routine 12-channel ECG: relation to age, physiological hemoglobin A 1C, triglycerides and SBP in healthy individuals.

Measurements of pulse wave velocity are generally thought to be too impractical for clinical routine. This study aimed to develop a method that can be performed during routine 12-channel ECG. A 12-channel ECG simultaneously supplies arterial impedance plethysmographic signals from the extremities beside segmental multifrequency impedance measurements for obtaining body composition. The origin of the plethysmographic signal (volume wave) at the arms and legs was determined at the level of the elbows and the knees. The volume wave velocity (VWV) at the aorta and femoral arteries was calculated from the time difference of the plethysmographic signals between arms and legs. Automated measurement of VWV was highly reproducible (r = 0.96). In 107 participants in perfect health, VWV in different models was positively related to age, physiological hemoglobin A 1C, triglycerides, normal standardized unattended blood pressure, but not to physiological low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Aortofemoral VWV was significantly higher in patients with established coronary artery disease than in healthy controls of the same age group (18.1 ± 5.8 vs. 11.9 ± 1.7 m/s, P < 0.001). VWV in study participants was higher than tonometrically determined pulse wave velocity as muscular arteries are included (13.2 ± 5.81 vs. 8.8 ± 2.98 m/s, n = 115, P < 0.001). These background arterial impedance plethysmographic measurements for the measurement of VWV made simultaneously during 12-channel ECG show promise for large-scale, routine clinical assessment of large artery function.

In Vivo Fat Quantification: Monitoring Effects of a 6-Week Non-Energy-Restricted Ketogenic Diet in Healthy Adults Using MRI, ADP and BIA.

The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was >2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat.

The hemodynamic impact of the bidirectional flow within calf perforators and conductive veins in varicose vein disease

The hemodynamic assessment of the bidirectional flow within calf perforators and in the conductive veins in varicose vein disease is presented. The bidirectional streaming within calf perforators is induced by the changing polarity of the systolic and diastolic pressure gradients arising during calf pump activity between the deep veins and the saphenous system of the lower leg, as documented by simultaneous pressure measurements in the posterior tibial vein and the great saphenous vein. This bidirectional flow makes the deep and superficial veins of the lower leg conjoined vessels. The vector of the bidirectional streaming in varicose vein patients is oriented inward, into the deep veins. The enlarged calf perforators are the consequence of the saphenous reflux; after elimination of saphenous reflux the diameter of calf perforators diminishes significantly. Results of venous pressure, plethysmographic and electromagnetic flow measurements rebut the still prevalent opinion that the outward flow within calf perforators is a reflux. There is an up-and-down flow in the conductive veins during calf pump activity with a prevailing systolic centripetal (orthograde) flow in the popliteal/femoral axis and a diastolic centrifugal (retrograde) flow in the incompetent great saphenous vein. The popliteal vein represents actually the drain pipe of the calf muscle pump. The ambulatory venous pressure gradient arising during the diastolic phase of the calf pump activity resembles the diastolic pressure difference between the aorta and the left ventricle.