Plethysmography Research Articles

Lung function outcomes in adults born extremely preterm across three decades of advancing perinatal medicine.

Advances in perinatal medicine from 1980 to 2000 improved survival in extremely preterm (EP) neonates. Long-term effects of these developments remain unclear, and we aimed to investigate potential cohort effects on adult lung function. Three 18-year-old population-based cohorts born at ≤28 weeks gestation or with birthweight ≤1000 g during 1982-85, 1991-92 and 1999-2000 and term-controls underwent spirometry, body plethysmography, and tests of lung diffusing capacity, bronchodilator reversibility, and airway hyperresponsiveness. We used Welch's t-tests to compare term- with EP-born as a group and split by bronchopulmonary dysplasia (BPD), and regression models to test group/cohort interactions. In all EP-born cohorts, z-scores for FEV1, FEV1/FVC, FEF25%-75%, DLCO and KCO were reduced compared with term-born. For the 82-85, 91-92 and 99-00 cohorts, deficits for z-FEV1 and z-DLCO were 1.23 and 0.53; 0.68 and 0.92; and 0.51 and 0.57, respectively (p ≤0.01 for all). Cohort analyses showed stable lung function across the three cohorts overall, but improvements across cohorts for the BPD subgroups in z-FEV1, z-FEV1/FVC, and z-FEF25%-75%. Adults born EP across three formative decades of neonatal care had stable lung function overall, with notable improvements in BPD subgroups across cohorts.

A decision rule for identifying patients at high risk for impaired lung diffusion capacity after COVID-19

Aim. To elaborate a decision rule for identifying the main predictors of impaired lung diffusion capacity after COVID-19. Materials and methods. The retrospective study included 341 patients without underlying lung diseases (median age 48 years) who experienced COVID-19 with bilateral pneumonia. The median extent of parenchymal lesion in the acute phase of COVID-19 (CTmax) was 50%. Spirometry, body plethysmography, and lung diffusion capacity for carbon monoxide (DLCO) test were performed. The data were analyzed by descriptive statistics, correlation analysis, one-dimensional logistic regression analysis with an assessment of odds ratios (OR), and multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess the quality of the binary classifier model.Results. The initial model for predicting reduced DLCO (< 80% of predicted) included the following predictors: CTmax, time interval from the COVID-19 onset, gender, age, body mass index. Backward stepwise regression was applied, and a binary classifier model that includes CTmax was obtained. The sensitivity and specificity of the model for the training sample were 80 and 67%, respectively, for the test sample – 79 and 70%, respectively. The analysis of OR showed that OR > 1 was observed at СTmax > 40%.Conclusion. The decision rule was obtained for predicting impaired lung diffusion capacity after COVID-19 with virus-associated lung damage in patients without underlying bronchopulmonary diseases. Patients with CTmax > 40% require more thorough clinical follow-up with DLCO monitoring after the acute phase of COVID-19

Silence of the lungs: comparing measures of slow and noncommunicating lung units from pulmonary function tests with computed tomography.

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of underventilated lung units (UVLU). In addition, we used two previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P < 0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249 mL [95% CI -10,796; 580 mL] and -203 mL [95% CI -997; 591 mL], respectively). Parameters from both spirometry and body plethysmography were suboptimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared with the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.NEW & NOTEWORTHY We consider the term "trapped air" either in the use of imaging or pulmonary function testing, something of a misnomer that can lead to an inaccurate assessment of an important physiological feature. Instead, we propose the term underventilated lung units (UVLU). Of the many pulmonary function methods we used in this study, we found that the use of multiple breath washout with short extension (MBWShX) to be the best nonimaging method.

Correlation between handgrip strength and air trapping in patients with stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) often presents with dyspnea resulting from the condition of air trapping, assessed by lung volume measurement studies. This study aimed to investigate the relationship between handgrip strength (HGS) and air trapping in COPD patients. Cross-sectional research was conducted in COPD patients at Thammasat University Hospital, Thailand between May 2022 and December 2023. HGS was assessed using the Jamar® Smart Hand Dynamometer, and air trapping was measured using a body plethysmograph. Air trapping was defined as a ratio of residual volume (RV) to total lung capacity (TLC) greater than 40%. Receiver operator characteristic (ROC) curves, sensitivity, and specificity values were calculated to determine the optimal cutoff value of HGS for predicting air trapping. A total of 72 patients (90.3% male) were included, with an average age of 72.4±9.7 years. The body mass index was 23.5±4.3 kg/m2. The smoking history was 23.2±14.8 pack-years. Common comorbidities included hypertension (36.1%) and diabetes (22.2%). Post-bronchodilator forced expiratory volume in 1 second (FEV1) was 72.1%±21.2%. Air trapping was found in 55.6%. A negative correlation was found between HGS and RV/TLC (R=-0.399, P=0.001). The best cutoff value for HGS to predict air trapping was 28.3 kg, with 71.9% sensitivity and 65.0% specificity. The area under the ROC curve for identifying air trapping was 0.681 (95% CI: 0.554 to 0.808, P=0.009). Air trapping is common in COPD patients, and HGS is significantly correlated with air trapping. Thus, HGS may serve as an alternative tool for assessing air trapping.

Home-based long-term physical endurance and inspiratory muscle training in children and adults with Fontan circulation.

Regular physical activity is highly recommended for patients with Fontan hemodynamics. Our aim was to investigate the effects of a long-term individualized home-based endurance training (IHET) on a bicycle ergometer in combination with inspiratory muscle training (IMT) in pediatric and adult patients after Fontan palliation. Additionally, factors influencing the trainability of Fontan palliated patients were analyzed. From 2018 to 2021 a single-center prospective study was performed initially including 25 Fontan palliated patients. During study period nine patients were excluded due to incompliance. A Magbike® bicycle ergometer (DKN Technology, France) was used for IHET and a POWERbreathe® Medic plus device (HaB GmbH, Germany) was utilized for the IMT. Over the study period, bike training was increased from 90 min of basic endurance training per week to additional 25 min of interval training per week. IMT consisted of 30 breaths per day for 6-7 days per week with pressure adaption over time. Patients underwent cardiopulmonary exercise testing (CPET) and body plethysmography including measurement of respiratory muscle strength at baseline and at follow-up examinations at 4, 10 and 22 months. Follow-up examinations were completed by 18/25 patients (72.0%) at 4 and 10 months and 16/25 patients (64.0%) at 22 months. Median exercise capacity slightly increased by 0.13 W/kg from baseline to last follow-up (p = 0.055, 95%CI: 0.0-0.36). However, a significant increase of oxygen pulse of 0.7 ml/beat (p = 0.006, 95%CI: 0.38-2.22) was detectable. IMT significantly improved respiratory function with an increase of inspiratory vital capacity (VCin/reference) by 4.0% (p = 0.016, 95%CI: 0.8-8). Median maximal inspiratory pressure increased by 1.2 kPa (p = 0.003, 95%CI: 0.64-3.19) and expiratory pressure by 1.5 kPa (p = 0.036, 95%CI: 0.08-2.29). No adverse events or unplanned interventions occurred during the study. Patients' subjective quality of life did not significantly change over the study period. In Fontan palliated patients, IHET in combination with IMT leads to a significant increase in oxygen pulse, inspiratory vital capacity as well as median maximal inspiratory and expiratory pressure but not to significant improvement of quality of life. Fontan patients should be encouraged to perform regular home-based exercise training.

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers.

Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations. Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE. The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P=0.038) and control individuals (14 ppb, P=0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P=0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment. Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Association of Preserved Ratio Impaired Spirometry with Arterial Stiffness.

Rationale: Preserved ratio impaired spirometry (PRISm) is a recently recognized spirometric pattern defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of at least 0.70 and a forced expiratory volume in 1 second <80% of reference. For unclear reasons, PRISm is associated with increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is a major mechanism of CV disease, which can be measured by carotid-femoral pulse-wave velocity (cfPWV). Objectives: We explored the hypothesis that cfPWV would be increased in individuals with PRISm and airflow limitation (AL). Methods: We measured forced spirometry, lung volumes by body plethysmography, and cfPWV in 9,466 subjects recruited from the general population in the Austrian cross-sectional LEAD (Lung, Heart, Social, Body) study and tested the association of arterial stiffness with PRISm and AL by multivariable linear regression analysis. Individuals younger than 18 years were excluded from the study. Results: Individuals with PRISm (n = 431; 4.6%) were of similar age to those with normal spirometry (n = 8,136; 85.9%) and significantly younger than those with AL (n = 899; 9.5%). Arterial hypertension, diabetes mellitus, coronary artery disease, heart failure, and peripheral arterial occlusive disease were significantly more common in individuals with PRISm than in those with normal lung function and similar to those with AL. There was a significant association between PRISm and arterial stiffness on bivariate linear regression analysis (crude model, β = 0.038; 95% confidence interval [CI], 0.016-0.058), which persisted after robust adjustment for clinical confounders upon multivariable analysis (final model, β = 0.017; 95% CI, 0.001-0.032). cfPWV was significantly higher in individuals with PRISm irrespective of the presence of established CV disease or pulmonary restriction. AL also showed a significant association with arterial stiffness on multivariable linear regression analysis (final model, β = 0.025; 95% CI, 0.009-0.042). Conclusions: Arterial stiffness measured by cfPWV is increased in individuals with PRISm independent of CV disease and risk factors. The pathobiological mechanisms underlying this association deserve further research.

Neue Empfehlungen zur Lungenfunktionsprüfung

New recommendations for pulmonary function testing – practical relevance for occupational medicine The latest German recommendations on pulmonary function diagnostics date back to 2015, when the guideline on spirometry was published. In 2022, an official document was published by the European Respiratory Society (ERS) in collaboration with the American Thoracic Society (ATS), in which new interpretations of routine lung function tests were presented. This affects spirometry, body plethysmography, diffusion capacity, the bronchodilation test and the reference values. The previous German recommendations for pulmonary function were therefore revised and published in March 2024. The German Respiratory Society (DGP), the German Lung Foundation, the German Respiratory League and the German Society for Occupational and Environmental Medicine (DGAUM) were involved in the revision of the recommendations under the leadership of Prof. Criée.

A Neural Basis for Mutant ATAXIN-1 Induced Respiratory Dysfunction in Mouse Models of Spinocerebellar Ataxia Type 1.

Spinocerebellar ataxia type 1 (SCA1), a dominantly inherited neurodegenerative disorder caused by an expanded trinucleotide repeat in the ATAXIN-1 (ATXN1) gene, is characterized by motor dysfunction, cognitive impairment, and death from compromised swallowing and respiration. To delineate specific cell types that contribute to respiratory dysfunction, we utilized the floxed conditional knock-in f-ATXN1 146Q/2Q mouse. Whole body plethysmography during spontaneous respiration and respiratory challenge showed that f-ATXN1 146Q/2Q mice exhibit a spontaneous respiratory phenotype characterized by elevated respiratory frequency, volumes, and respiratory output. Consequently, the ability of f-ATXN1 146Q/2Q mice to increase ventilation during the challenge is impaired. To investigate the role of mutant ATXN1 expression in neural and skeletal muscle lineages, f-ATXN1 146Q/2Q mice were bred to Nestin-Cre and Acta1-Cre mice respectively. These analyses revealed that the abnormal spontaneous respiration in f-ATXN1 146Q/2Q mice involved two aspects: a behavioral phenotype in which SCA1 mice exhibit increased motor activity during respiratory testing and functional dysregulation of central respiratory control centers. Both aspects of spontaneous respiration were partially ameliorated by removing mutant ATXN1 from neural, but not skeletal muscle, cell lineages.

Assessment and monitoring of lung disease in patients with severe alpha 1 antitrypsin deficiency: a european delphi consensus of the EARCO group

BackgroundCurrently, there is conflicting information and guidance on the effective management of Alpha 1 Antitrypsin Deficiency (AATD). Establishing a consensus of assessment and disease management specific to AATD is important for achieving a standardized treatment pathway and for improving patient outcomes. Here, we aim to utilize the Delphi method to establish a European consensus for the assessment and management of patients with severe AATD.MethodsTwo rounds of a Delphi survey were completed online by members of the European Alpha-1 Research Collaboration (EARCO). Respondents were asked to indicate their agreement with proposed statements for patients with no respiratory symptoms, stable respiratory disease, and worsening respiratory disease using a Likert scale of 1–7. Levels of agreement between respondents were calculated using a weighted average.ResultsRound 1 of the Delphi survey was sent to 103 members of EARCO and 38/103 (36.9%) pulmonologists from across 15 countries completed all 109 questions. Round 2 was sent to all who completed Round 1 and 36/38 (94.7%) completed all 79 questions. Responses regarding spirometry, body plethysmography, high-resolution computed tomography, and the initiation of augmentation therapy showed little variability among physicians, but there was discordance among other aspects, such as the use of low-dose computed tomography in both a research setting and routine clinical care.ConclusionsThese results provide expert opinions for the assessment and monitoring of patients with severe AATD, which could be used to provide updated recommendations and standardized treatment pathways for patients across Europe.

The pontine Kölliker-Fuse nucleus is important for reduced post-inspiratory airflow elicited by stimulation of the ventral respiratory parafacial region.

Considering that the retrotrapezoid nucleus/respiratory parafacial region (RTN/pFRG) would be an important center in the central nervous system involved in the maintenance and modulation of respiratory activity, we hypothesized that neurons in this nucleus would also be involved in the postinspiratory phase of the respiratory cycle through a connection with the pontine Kölliker-Fuse (KF) region. Here we performed pharmacogenetic manipulation (AAV-hM3D(Gq)-mCherry or AAV-hM4D(Gi)-mCherry) in VGlut2-cre, Ai6 conscious mice to evaluate breathing parameters through whole body plethysmography under baseline conditions (normoxia: FiO2 = 0.21) or under hypercapnia or hypoxia challenges (FiCO2 = 0.07 or FiO2 = 0.08). Under normoxia, selective stimulation of RTN/pFRG resulted in a smaller increase in VE (1,272 ± 102.5, vs. RTN/pFRG stimulation: 1,878 ± 122.1 ml/kg/min), due to a smaller increase in VT (5.4 ± 0.35, vs. RTN/pFRG stimulation: 7.77 ± 0.21 ml/kg) without changing fR in a condition of KF inhibition. However, inhibition of the VGlut2 neurons in the KF did affect the TE1 produced by selective activation of RTN/pFRG (119.9 ± 2.53, vs. RTN/pFRG stimulation: 104 ± 2.46 ms). Both the hypercapnia and hypoxia ventilatory response were reduced after inhibition of VGlut2-expressing KF neurons. Therefore, consistent with anatomical projections RTN/pFRG neurons regulate lung ventilation by controlling all aspects of breathing, i.e breathing frequency, inspiration, postinspiration and active expiration. All the modulation seems to be dependent on the integrity of the glutamatergic neurons in the KF region.

Prediction of nocturnal ventilation by pulmonary function testing in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) prognosis is poor due to progressive weakening of the respiratory muscles. Survival and quality of life can be improved by noninvasive ventilation (NIV), which is initially applied while sleeping. The indication for NIV is based on pulmonary function testing (PFT) and polysomnography (PSG) with capnography (tCO2). While it is desirable to predict nocturnal ventilation by waking PFT in ALS, the parameters suited for reliable predictions remain elusive. We retrospectively analyzed parameters derived from PFT (spirometry, body plethysmography, diffusion capacity, respiratory muscle testing) and blood gas analysis, PSG and tCO2 in 42 patients with ALS (27 men, 15 women, age 69 ± 12.1 years) and performed Spearman's correlation analysis of daytime waking parameters and nighttime sleep parameters. 28 patients (66.7%) showed restrictive impairment of ventilation and 15 patients (48.3%) showed insufficiency of the respiratory musculature. There was no obstructive impairment of ventilation. We did not observe any significant correlations between any single daytime PFT parameter with nocturnal pCO2. However, there were significant correlations between the ratios PIF/PEF, MEF50/MIF50, DLCO/VA as well as FEV1/FVC and nocturnal pCO2. Highly normal FEV1/FVC and Krogh-Factor (DLCOc/VA) indicated nocturnal hypercapnia. Furthermore, waking hypercapnia, concentrations of bicarbonate and base excess were each positively correlated with nocturnal hypercapnia. Waking PFT is not a good predictor of nocturnal ventilation. Inspiratory parameters as well as the ratios FEV1/FVC and DLCO/VA performed best and should be included in the interpretation. Our analyses confirm the relevance of inspiratory muscle weakness in ALS. PSG and tCO2 remain the gold standard for the assessment of nocturnal ventilation.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease

BackgroundIn advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD.MethodsThis monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters’ diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI].ResultsFVC% (AUROC 0.77 [95%CI 0.72–0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70–0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58–0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93–0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94–0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values.ConclusionsRoutinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Effect of adenosinergic manipulations on amygdala-kindled seizures in mice: Implications for sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) results in more years of potential life lost than any neurological condition with the exception of stroke. It is generally agreed that SUDEP happens due to some form of respiratory, cardiac, and electrocerebral dysfunction following a seizure; however, the mechanistic cause of these perturbations is unclear. One possible explanation lies with adenosinergic signaling. Extracellular levels of the inhibitory neuromodulator adenosine rapidly rise during seizures, a countermeasure that is necessary for seizure termination. Previous evidence has suggested that excessive adenosinergic inhibition could increase the risk of SUDEP by silencing brain areas necessary for life, such as the respiratory nuclei of the brainstem. The goal of this investigation was to further clarify the role of adenosine in seizure-induced respiratory and electrocerebral dysfunction. To determine the role of adenosine in postictal physiological dysregulation, we pharmacologically manipulated adenosine signaling prior to amygdala-kindled seizures in mice while recording electroencephalogram (EEG), electromyogram, and breathing using whole body plethysmography. The adenosinergic drugs used in this study included selective and nonselective adenosine receptor antagonists and inhibitors of adenosine metabolism. We found that high doses of adenosine receptor antagonists caused some seizures to result in seizure-induced death; however, counterintuitively, animals in these conditions that did not experience seizure-induced death had little or no postictal generalized EEG suppression. Inhibitors of adenosine metabolism had no effect on postictal breathing but did worsen some postictal electrocerebral outcomes. The unexpected effect of high doses of adenosine antagonists on seizure-induced death observed in this study may be due to the increase in seizure severity, vasoconstriction, or phosphodiesterase inhibition caused by these drugs at high doses. These findings further clarify the role of adenosine in seizure-induced death and may have implications for the consumption of caffeine in epilepsy patients and the prevention of SUDEP.

Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons

Failure to recover from repeated hypercapnia and hypoxemia (HH) challenges caused by severe GCS and postictal apneas may contribute to sudden unexpected death in epilepsy (SUDEP). Our previous studies found orexinergic dysfunction contributes to respiratory abnormalities in a preclinical model of SUDEP, Kcna1−/− mice. Here, we developed two gas challenges consisting of repeated HH exposures and used whole body plethysmography to determine whether Kcna1−/− mice have detrimental ventilatory responses. Kcna1−/− mice exhibited an elevated ventilatory response to a mild repeated hypercapnia-hypoxia (HH) challenge compared to WT. Moreover, 71% of Kcna1−/− mice failed to survive a severe repeated HH challenge, whereas all WT mice recovered. We next determined whether orexin was involved in these differences. Pretreating Kcna1−/− mice with a dual orexin receptor antagonist rescued the ventilatory response during the mild challenge and all subjects survived the severe challenge. In ex vivo extracellular recordings in the lateral hypothalamus of coronal brain slices, we found reducing pH either inhibits or stimulates putative orexin neurons similar to other chemosensitive neurons; however, a significantly greater percentage of putative orexin neurons from Kcna1−/−mice were stimulated and the magnitude of stimulation was increased resulting in augmentation of the calculated chemosensitivity index relative to WT. Collectively, our data suggest that increased chemosensitive activity of orexin neurons may be pathologic in the Kcna1−/− mouse model of SUDEP, and contribute to elevated ventilatory responses. Our preclinical data suggest that those at high risk for SUDEP may be more sensitive to HH challenges, whether induced by seizures or other means; and the depth and length of the HH exposure could dictate the probability of survival.

Overexpression of USP8 inhibits inflammation and ferroptosis in chronic obstructive pulmonary disease by regulating the OTUB1/SLC7A11 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a familiar disease, and owns high morbidity and mortality, which critically damages the health of patients. Ubiquitin-specific peptidase 8 (USP8) is a pivotal protein to join in the regulation of some diseases. In a previous report, it was determined that USP8 expression is down-regulated in LPS-treated BEAS-2B cells, and USP8 restrains inflammatory response and accelerates cell viability. However, the regulatory roles of USP8 on ferroptosis in COPD are rarely reported, and the associated molecular mechanisms keep vague. To investigate the regulatory functions of USP8 in COPD progression. The lung functions were measured through the Buxco Fine Pointe Series Whole Body Plethysmography (WBP). The Fe level was tested through the Fe assay kit. The protein expressions were assessed through western blot. The levels of tumor necrosis -factor-α, interleukin 6, and interleukin 8 were evaluated through enzyme-linked immunosorbent serologic assay. Cell viability was tested through CCK-8 assay. In this work, it was discovered that overexpression of USP8 improved lung function in COPD mice. In addition, overexpression of USP8 repressed ferroptosis by regulating glutathione peroxidase 4 and acyl-CoA synthetase long-chain family 4 expressions in COPD mice. Overexpression of USP8 suppressed inflammation in COPD mice. Furthermore, overexpression of USP8 suppressed ferroptosis in COPD cell model. At last, it was verified that overexpression of USP8 accelerated ubiquitin aldehyde-binding protein 1 (OTUB1)/solute carrier family 7 member 11 (SLC7A11) pathway. This study manifested that overexpression of USP8 restrained inflammation and ferroptosis in COPD by regulating the OTUB1/SLC7A11 signaling pathway. This discovery hinted that USP8 could be a potential target for COPD treatment.

Effect of Cholinergic Receptor Antagonists on the Potentiation of the Effect of Adenosine Receptor Blockers in People with Bronchial Asthma

Background: The interaction between adenosine receptor blockers and anticholinergic substances in the treatment of bronchial asthma is an area of interest. The efficacy of such combinations in managing bronchial asthma and bronchial hypersensitivity needs to be explored further. Understanding lung function parameters such as airway resistance and intrathoracic gas volume is crucial for evaluating the effects of these medications. Objective: This study aimed to investigate the effect of combining the adenosine receptor blocker, bamifylline, with the anticholinergic substance, ipratropium bromide spray, in patients with bronchial asthma. Specifically, the study sought to assess changes in lung function parameters, including airway resistance and intrathoracic gas volume, after administering ipratropium bromide alone and in combination with bamifylline. Methods: Sixteen patients with bronchial asthma were enrolled in the study. Lung function was evaluated using body plethysmography, with measurements of airway resistance (Raw), intrathoracic gas volume (ITGV), airway specific resistance (SRaw), and airway specific conductance (SGaw). Patients initially received ipratropium bromide inhalation (2 inhalations x 20µg), followed by Raw and ITGV measurements at intervals (5, 30, 60, and 120 minutes). Subsequently, patients received bamifylline (2 x 600 mg) daily for seven days at home. On the eighth day, they were administered ipratropium bromide spray (2 inhalations x 20µg), and lung function parameters were assessed similarly. Results: Administration of ipratropium bromide alone led to a significant reduction in airway resistance (p&lt;0.05). However, the combination of ipratropium bromide with bamifylline did not significantly enhance the effects of adenosine receptor blockade (p&lt;0.05). Specifically, there were no significant changes in Raw, ITGV, SRaw, or SGaw after combining ipratropium bromide with bamifylline. Conclusion: The study findings suggest that the addition of anticholinergic substances did not potentiate the action of adenosine receptor blockers in patients with bronchial asthma. Therefore, the anti-inflammatory effects of xanthines, such as bamifylline, were not augmented by anticholinergic substances in this study. These results highlight the need for further research to explore alternative therapeutic approaches in the management of bronchial asthma.

Impact of elexacaftor/tezacaftor/ivacaftor combination therapy on body plethysmography in adults with cystic fibrosis: Beyond FEV&lt;sub&gt;1&lt;/sub&gt;

Impact of elexacaftor/tezacaftor/ivacaftor combination therapy on body plethysmography in adults with cystic fibrosis: Beyond FEV&lt;sub&gt;1&lt;/sub&gt;

Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model – the mdx mouse – is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function.

Systemic Manifestations of COPD and the Impact of Dual Bronchodilation with Tiotropium/Olodaterol on Cardiac Function and Autonomic Integrity.

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 μg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests' results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests' results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m2 (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study.