Respiratory System Resistance Research Articles

Effect of different lung recruitment strategies and airway device on oscillatory mechanics in children under general anaesthesia.

Atelectasis has been reported in 68 to 100% of children undergoing general anaesthesia, a phenomenon that persists into the recovery period. Children receiving recruitment manoeuvres have less atelectasis and fewer episodes of oxygen desaturation during emergence. The optimal type of recruitment manoeuvre is unclear and may be influenced by the airway device chosen. We aimed to investigate the different effects on lung mechanics as assessed by the forced oscillation technique (FOT) utilising different recruitment strategies: repeated inflations vs. one sustained inflation and different airway devices, a supraglottic airway device vs. a cuffed tracheal tube. Pragmatic enrolment with randomisation to the recruitment strategy. We conducted this single-centre trial between February 2020 and March 2022. Seventy healthy patients (53 boys) aged between 2 and 16 years undergoing general anaesthesia were included. Forced oscillations (5 Hz) were superimposed on the ventilator waveform using a customised system connected to the anaesthesia machine. Pressure and flow were measured at the inlet of the airway device and used to compute respiratory system resistance and reactance. Measurements were taken before and after recruitment, and again at the end of surgery. The primary endpoint measured is the change in respiratory reactance. Statistical analysis (linear model with recruitment strategy and airway device as factors) did not show any significant difference in resistance and reactance between before and after recruitment. Baseline reactance was the strongest predictor for a change in reactance after recruitment: prerecruitment Xrs decreases by mean (standard error) of 0.25 (0.068) cmH2O s l-1 per 1 cmH2O-1 s l-1 increase in baseline Xrs (P < 0.001). After correcting for baseline reactance, the change in reactance after recruitment was significantly lower for sustained inflation compared with repeated inflation by mean (standard error) 0.25 (0.101) cmH2O (P = 0.0166). Although there was no significant difference between airway devices, this study demonstrated more effective recruitment via repeated inflations than sustained inflation in anaesthetised children. Australian New Zealand Clinical Trials Registry: ACTRN12619001434189.

Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model.

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

A novel method to quantify breathing effort from respiratory mechanics and esophageal pressure.

Breathing effort is important to quantify to understand mechanisms underlying central and obstructive sleep apnea, respiratory-related arousals, and the timing and effectiveness of invasive or non-invasive mechanically assisted ventilation. Current quantitative methods to evaluate breathing effort rely on inspiratory esophageal or epiglottic pressure swings or changes in diaphragm electromyographic (EMG) activity, where units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method to quantify breathing effort in units directly comparable to measured ventilation by applying respiratory mechanics first principles to convert continuous transpulmonary pressure measurements into "attempted" airflow expected to have arisen without upper airway obstruction. The method was evaluated using data from eleven subjects undergoing overnight polysomnography, including 6 obese patients with severe obstructive sleep apnea (OSA), including one who also had frequent central events, and 5 healthy-weight controls. Classic respiratory mechanics showed excellent fits of airflow and volume to transpulmonary pressures during wake periods of stable unobstructed breathing (mean ± SD r² = 0.94 ± 0.03), with significantly higher respiratory system resistance in patients compared to healthy controls (11.2 ± 3.3 vs 7.1 ± 1.9 cmH2O·l-1·sec, P=0.032). Subsequent estimates of attempted airflow from transpulmonary pressure changes clearly highlighted periods of acute and prolonged upper airway obstruction, including within the first few breaths following sleep onset in patients. This novel technique provides unique quantitative insights into the complex and dynamically changing inter-relationships between breathing effort and achieved airflow during periods of obstructed breathing in sleep.

Effect of TRPV4 Antagonist GSK2798745 on Chlorine Gas-Induced Acute Lung Injury in a Swine Model.

As a regulator of alveolo-capillary barrier integrity, Transient Receptor Potential Vanilloid 4 (TRPV4) antagonism represents a promising strategy for reducing pulmonary edema secondary to chemical inhalation. In an experimental model of acute lung injury induced by exposure of anesthetized swine to chlorine gas by mechanical ventilation, the dose-dependent effects of TRPV4 inhibitor GSK2798745 were evaluated. Pulmonary function and oxygenation were measured hourly; airway responsiveness, wet-to-dry lung weight ratios, airway inflammation, and histopathology were assessed 24 h post-exposure. Exposure to 240 parts per million (ppm) chlorine gas for ≥50 min resulted in acute lung injury characterized by sustained changes in the ratio of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen concentration (PaO2/FiO2), oxygenation index, peak inspiratory pressure, dynamic lung compliance, and respiratory system resistance over 24 h. Chlorine exposure also heightened airway response to methacholine and increased wet-to-dry lung weight ratios at 24 h. Following 55-min chlorine gas exposure, GSK2798745 marginally improved PaO2/FiO2, but did not impact lung function, airway responsiveness, wet-to-dry lung weight ratios, airway inflammation, or histopathology. In summary, in this swine model of chlorine gas-induced acute lung injury, GSK2798745 did not demonstrate a clinically relevant improvement of key disease endpoints.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study

BackgroundThe clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.MethodsParticipants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ − 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ − 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.ResultsThis study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.ConclusionsThe participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Effect of increased resistance on dynamic compliance assessed by two clinical monitors during volume-controlled ventilation: A test-lung study

ObjectiveTo evaluate the effect of increased respiratory system resistance (RRS) on dynamic compliance (Cdyn) assessed by the NM3 monitor (Cdyn(NM3)) and the E-CAiOV module (Cdyn(ECAiOV)). Study designProspective laboratory study. MethodsA training test lung (TTL) simulated the mechanical ventilation of a mammal with 50 and 300 mL tidal volumes in three conditions of RRS [normal (RBL), moderately increased (R1) and severely increased (R2)] and a wide range of clinically relevant Cdyn. Simulations at increased RRS were paired with simulations at RBL with the same static compliance for comparisons. Pearson’s correlation coefficient and concordance correlation coefficient between the measurements at RBL with the ones with increased RRS were calculated. Bland–Altman plots were also used to evaluate the agreement of Cdyn(ECAiOV) and Cdyn(NM3) at RBL (control values) with their paired values at R1 and R2. Relative bias and limits of agreement (LOAs) were calculated and LOAs larger than 30% were considered unacceptable. Trending ability of Cdyn(NM3) and Cdyn(ECAiOV) were evaluated by polar plots. Values of p < 0.05 were considered significant. ResultsThe effect of increased RRS was more pronounced for Cdyn(ECAiOV) than for Cdyn(NM3). Unacceptable agreement was only observed in Cdyn(NM3) at R2 in the 300 mL simulation (bias = –18.3% and lower LOA = –45%). For Cdyn(ECAiOV), agreement was unacceptable for all tested RRS in both simulations, being the worst at R2 in the 300 mL simulation (bias = –54.7% and lower LOA = –100.2%). Both levels of increased RRS caused poor trending ability for Cdyn(ECAiOV), whereas the same effect was only observed for Cdyn(NM3) at R2. Conclusions and clinical relevanceIn the presence of increased RRS, Cdyn estimated by the NM3 monitor presented better capability to distinguish between changes in RRS from changes in respiratory system compliance.

A pilot study to assess the effects of preventing fluid retention in the legs by wearing compression stockings on overnight airway narrowing in mild asthma.

Nocturnal asthma is a sign of asthma worsening and could be partially due to more fluid drawn into the thorax during sleep by gravitational force and/or pharyngeal collapse in those with obstructive sleep apnea. Wearing compression stockings during the day reduces fluid shift from the legs to the neck overnight. However, the potential effect of wearing compression stockings to reduce fluid accumulation in the leg and to improve nocturnal small airway narrowing in patients with asthma has not been investigated. This study investigates whether reducing leg fluid volume by wearing compression stockings during the day would attenuate small airway narrowing in patients with asthma before and after sleep. We enrolled 11 participants with asthma. All participants underwent overnight polysomnography with or without wearing compression stockings for 2weeks. Before and after sleep, leg fluid volume (LFV) was measured by bioelectrical impedance, and airway narrowing was primarily assessed by respiratory system resistance and reactance at 5Hz (R5 and X5 respectively) using oscillometry. After 2weeks of wearing compression stockings, the LFV measured in the evening was reduced (∆ = - 192.6 ± 248.3ml, p = 0.02), and R5 and X5 improved (∆ = - 0.7 ± 0.9 cmH2O/L/s, p = 0.03 and 0.2 ± 1.4 cmH2O/L/s, p = 0.05 respectively). No changes were observed in the morning. Preventing fluid retention in the legs by wearing compression stockings for 2weeks during the day, reduced LFV and airway narrowing in the evening in all participants with asthma, but not in the morning after sleep.

Could CPAP Devices Be Used to Ventilate Cardiac Arrest Patients? A Bench Study

Objectives To investigate the potential efficacy of a commercial continuous positive airway pressure (CPAP) ventilator to provide effective respiratory support in a simulated scenario of out-of-hospital cardiac arrest (OHCA). Methods The study was conducted on a high-fidelity manikin (SimMan 3 GTM, Laerdal, NOR) connected to the ASL 5000TM Lung Simulator (IngMar Medical, USA). To simulate OHCA, we set no spontaneous respiratory acts and physiological respiratory system resistance (13 cmH2O/L.sec) and compliance (50 mL/cmH2O). The Respironics BiPAP A40 ventilatorI (Philips, NL) was used to provide ventilatory support while operating in CPAP mode. Tests were performed at different values of positive pressure of the CPAP ventilator (PCPAP: 5, 7.5, 10, 12.5 and 15 cmH2O) and the intrapulmonary volume (tidal volume, Vt) measured via the simulator software computer interface. A trained physician performed the tests. Our primary outcome was a VT of ≈500-600 mL with an intermittent maneuver simulating cardiopulmonary resuscitation (CPR)-like ventilatory support practice according to international guideline-based target (1-sec ventilation followed by 1-sec pause). Results In intermittent ventilatory support tests, PCPAP levels of 12.5, and 15 cmH2O resulted in a VT equal to 508 ± 13 mL, and 557 ± 44 mL respectively (p = 0.04), thus approaching the VT target. Conclusions We provide preliminary evidence of the potential efficacy of CPAP ventilators designed for home use to provide effective respiratory support to a simulated respiratory arrest patient.

Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is characterized by impaired lung development with sustained functional abnormalities due to alterations of airways and the distal lung. Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about the underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of the airways and parenchyma, contributes to late respiratory disease as a result of antenatal stress is unknown. We hypothesized that antenatal endotoxin (ETX) impairs juvenile lung function as a result of altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intraamniotic ETX (10 μg) or saline solution (control) 2 days before term. We performed extensive structural and functional evaluation of the proximal airways and distal lung in 2-week-old rats. Distal lung structure was quantified by stereology. Conducting airway diameters were measured using micro-computed tomography. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. ETX-exposed pups exhibited distal lung simplification, decreased alveolar surface area, and decreased parenchyma-airway attachments. ETX-exposed pups exhibited decreased tracheal and second- and third-generation airway diameters. ETX increased respiratory system resistance and decreased lung compliance at baseline. Only Newtonian resistance, specific to large airways, exhibited increased methacholine reactivity in ETX-exposed pups compared with controls. ETX-exposed pups had a decreased ratio of FEV in 0.1 second to FVC and a normal FEV in 0.1 second, paralleling the clinical definition of dysanapsis. Antenatal ETX causes abnormalities of the central airways and distal lung growth, suggesting that dysanapsis contributes to abnormal lung function in juvenile rats.

Impulse oscillometry in patients with pulmonary arterial hypertension: an exploratory study

IntroductionStudies suggest peripheral airway abnormalities in Pulmonary Arterial Hypertension (PAH). Impulse Oscillometry (IOS) is a noninvasive and sensitive technique for assessing the small airways. It evaluates the impedance of the respiratory system ‒ Resistance (R) and reactance (X) ‒ to a pulse of sound waves sent to the lungs, in a range of frequencies (5‒20 Hz). MethodResistance variables: R5, R20, R5-R20 and reactance variables: AX (reactance area) and Fres (resonance frequency). The aim is to evaluate R and X in patients with idiopathic PAH (IPAH) and to investigate whether there is a correlation between IOS and spirometry. ResultsThirteen IPAH patients and 11 healthy subjects matched for sex and age underwent IOS and spirometry. IPAH patients had lower FVC and FEV1 values (p < 0.001), VEF1/CVF (p = 0.049) and FEF 25-75 (p = 0.006) than healthy patients. At IOS, IPAH patients showed lower tidal volumes and higher AX (p < 0.05) compared to healthy individuals, and 53.8 of patients had R5-R20 values ≥ 0.07 kPa/L/s. Correlation analysis: X5, AX, R5-R20 and Fres showed moderate correlation with FVC (p = 0.036 r = 0.585, p = 0.001 r = -0.687, p = 0.005 r = -0.726 and p = 0.027 r = -0.610); Fres (p = 0.012 r = -0.669) and AX (p = 0.006 r = -0.711) correlated with FEV1; [R5 and R20, (R5-R20)] also correlated with FEV1 (p < 0.001 r = -0.573, p = 0.020 r = -0.634 and p = 0.010 r = -0.683, respectively) in the IPAH group. There were also moderate correlations of FEF 25–75 % with Z5 (p = 0.041), R5 (p = 0.018), Fres (p = 0.043) and AX (p = 0.023). DiscussionPatients showed changes suggestive of increased resistance and reactance in the IOS compared to healthy individuals, and the IOS findings showed a good correlation with spirometry variables.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. NCT05812196.

Ventilator hyperinflation associated with flow bias optimization in the bronchial hygiene of mechanically ventilated patients

Background: Ventilation configurations are of great clinical importance for adequate outcomes in mechanically ventilated patients, and they may even be used as specific physical therapy techniques.Objectives: To compare the effectiveness of lung hyperinflation through mechanical ventilation (HMV) with HMV plus flow bias optimization regarding respiratory mechanics, hemodynamics, and volume of secretion.Methods: Patients mechanically ventilated > 24 h were included in this randomized crossover clinical trial. The following techniques were applied: HMV alone (control group) and HMV plus flow bias optimization (intervention group).Results: The 20 included patients underwent both techniques, totaling 40 collections. A total of 52 % were women, the mean age was 60.8 (SD, 15.7) years, and the mean mechanical ventilation time was 4.3 (SD, 3.0) days. The main cause of mechanical ventilation was sepsis (44 %). Expiratory flow bias in optimized HMV was higher. than conventional HMV (p < 0.001). The volume of tracheal secretions collected was higher during optimized than conventional HMV. (p = 0.012). Significant differences in peak flow occurred at the beginning of the technique and a there was a significant decrease in respiratory system resistance immediately and 30 min after applying the technique in the intervention group.Conclusions: The volume of tracheal secretions collected was higher during optimized HMV, and, HMV with flow bias optimization resulted in lower respiratory system resistance and flow peaks and produced expiratory flow bias.

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

BackgroundTyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment.MethodsTension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting.ResultsWe discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice.ConclusionIn summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

Intact cord resuscitation in newborns with congenital diaphragmatic hernia: insights from a lamb model.

Congenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics. At 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h. CDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), p < 0.05, and right lung-to-body weight ratio of 8.2 (3.1), p < 0.05. They reached lower Vt/kg (tidal volume per kg) during the course of the resuscitation period with 1.2 (0.7) ml/kg at 10 min and 3 (1.65) ml/kg at 60 min (p < 0.05). Compliance of the respiratory system was lower in CDH lambs with 0.5 (0.3) ml/cmH2O at 60 min (p < 0.05) and 0.9 (0.26) ml/cmH2O at 120 min (p < 0.05). Differences between pre- and postductal SpO2 were higher with 15.1% (21.4%) at 20 min and 6.7% (14.5%) at 80 min (p < 0.05). CDH lambs had lower differences between inspired and expired oxygen fractions with 4.55% (6.84%) at 20 min and 6.72% (8.57%) at 60 min (p < 0.05). CDH lamb had lower left ventricle [2.73 (0.5) g/kg, p < 0.05] and lower right ventricle [0.69 (0.8), p < 0.05] to left ventricle ratio. CDH lambs had significantly lower tidal volume than control lambs due to lower compliance of the respiratory system and higher airway resistance. These respiratory changes are characteristic of CDH infants and are associated with higher mortality rates. CDH lambs also exhibited pulmonary hypertension, pulmonary hypoplasia, and left ventricle hypoplasia, consistent with observations in human newborns. To conclude, our lamb model successfully provides a reliable representation of CDH and can be used to study its pathophysiology and potential interventions.

Is mechanical power an under-recognised entity within the preterm lung?

BackgroundMechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated.Hypothesis-generating data setTo provide a justification for our hypothesis, data in a repository at the Murdoch Children’s Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124–127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation.ResultsAll components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth.ConclusionsIn our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis.

Association of forced oscillation technique measurements with respiratory system compliance and resistance in a 2-compartment physical model

BackgroundThe forced oscillation technique (FOT) may be useful for diagnosis and follow-up of respiratory diseases. It is unclear how global or regional alterations in airway resistance (Raw) and lung compliance (CL) alter FOT measurements. MethodsA 2-compartment physical model of the respiratory system allowed to simulate variations in Raw, CL, and their heterogeneity during tidal breathing in an adult human. Five-Hz respiratory system resistance (Rrs5) and reactance (Xrs5), area of reactance (AX), resonance frequency (Fresp) and intrabreath variation in Rrs5 and Xrs5 were measured by FOT. Frequency dependance of resistance could not be studied in this model. Relationships between model characteristics (Raw, CL, and heterogeneity) and FOT measurements were explored by multiple regression. ResultsRrs5 and intrabreath variation in Rrs5 and Xrs5 strongly associated with model characteristics (R2=0.753, 0.5 and 0.658). Associations of Xrs5, AX, and Fresp with model characteristics were weak (R2=0.214, 0.349 and 0.076). Raw heterogeneity was the main determinant of Rrs5 (Coeff=0.594), AX (Coeff=0.566) and intrabreath variation in Rrs5 and Xrs5 (Coeff=0.586 and 0.732). Regional extremes in Raw strongly determined Rrs5 (Coeff=1.006). Xrs5 did not strongly associate with any model characteristic. ConclusionRaw heterogeneity and maximal regional Raw were the main determinants of FOT measurements, in particular Rrs5. Associations between CL and FOT measurements were weak.

Parameterisation of Respiratory Impedance in Lung Cancer Patients From Forced Oscillation Lung Function Test.

This study aims to analyze the contribution and application of forced oscillation technique (FOT) devices in lung cancer assessment. Two devices and corresponding methods can be feasible to distinguish among various degrees of lung tissue heterogeneity. The outcome respiratory impedance Zrs (in terms of resistance Rrs and reactance Xrs) is calculated for FOT and is interpreted in physiological terms by being fitted with a fractional-order impedance mathematical model (FOIM). The non-parametric data obtained from the measured signals of pressure and flow is correlated with an analogous electrical model to the respiratory system resistance, compliance, and elastance. The mechanical properties of the lung can be captured through Gr to define the damping properties and Hr to describe the elastance of the lung tissue, their ratio representing tissue heterogeneity ηr. We validated our hypotheses and methods in 17 lung cancer patients where we showed that FOT is suitable for non-invasively measuring their respiratory impedance. FOIM models are efficient in capturing frequency-dependent impedance value variations. Increased heterogeneity and structural changes in the lungs have been observed. The results present inter- and intra-patient variability for the performed measurements. The proposed methods and assessment of the respiratory impedance with FOT have been demonstrated useful for characterizing mechanical properties in lung cancer patients. This correlation analysis between the measured clinical data motivates the use of the FOT devices in lung cancer patients for diagnosis of lung properties and follow-up of the respiratory function modified due to the applied radiotherapy treatment.

Sensitive methods for assessment of lung health in welders and controls

BackgroundWelders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. MethodsThis study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). ResultsAccording to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. ConclusionsThis study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Premature monochorionic monoamniotic twins have lower lung compliance at birth than matched dichorionic diamniotic twins.

Premature infants are born with immature lungs that demonstrate abnormal pulmonary function with differences in passive respiratory system compliance and resistance, and functional residual capacity. To our knowledge, no studies have evaluated differences in neonatal pulmonary function based on the type of twin gestation, or chorionicity. Given the effect of chorionicity on outcomes, we aimed to study the effect of twin type, monochorionic monoamniotic (MCMA) vs dichorionic diamniotic (DCDA), on neonatal early pulmonary function tests. In this prospective cohort study, 5 sets of DCDA twins were matched to 5 sets of MCMA twins on gestational age at delivery, latency from antenatal corticosteroid exposure, birthweight, race and gender. Mean values were compared for passive respiratory system compliance and resistance, functional residual capacity, and tidal volume. MCMA infants had a significantly lower compliance (0.64 vs 1.25 mL/cm H2O /kg; p = 0.0001) and significantly higher resistance (0.130 vs 0.087 cm H2O /mL/sec; p = 0.0003) than DCDA infants. Functional residual capacity was lower for MCMA than DCDA infants (17.5 vs 23.4 mL/kg; p = 0.17). Further, 80% of MCMA infants required intubation for surfactant administration compared to 20% of DCDA infants, indicating the clinical significance of these objective measures. Due to the matched case-control design, causality cannot be established. However, we speculate that these differences in lung function may derive from differential exposure to preterm labor and endogenous maternal corticosteroid exposure. Further study is necessary to establish the true causal relationship.

Para-Cyclists Present Impaired Lung Function and Mechanics Independent of Peripheral and Respiratory Muscle Strength

Objective: The present study investigated the possible changes in respiratory function and mechanics in paralympic cyclists in comparison with cyclists. Design: Lung function (spirometry) and mechanics (impulse oscillometry) pre- and post-bronchodilator, the levels of FeNO and the peripheral and respiratory muscle strength were evaluated in paralympic cyclists [spinal injury from C5 (incomplete injury) until T11 (complete injury); (n=8)] and cyclists (n=12). Results: Paralympic cyclists presented reduced FVC, FEV1, PEF, VC In and MEF75%. Of note, only athletes presented response to bronchodilator, as observed for FEV and for FVC/FEV1. Respiratory impedance (Z5Hz), total respiratory system resistance (R5Hz) was impaired in paralympic cyclists. No differences were found hand grip and respiratory muscle strength and for FeNO comparing paralympic cyclists with cyclists. Conclusion: We conclude that para-cyclists present impaired lung function and mechanics and that such impairments are not correlated with reduction in the respiratory or peripheral muscle strength or with pulmonary inflammation.