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Aging invariably decreases sensory and motor stimuli and affects several neuronal systems and their connectivity to key brain regions, including those involved in breathing. Nevertheless, further investigation is needed to fully comprehend the link between senescence and respiratory function. Here, we investigate whether a mouse model of accelerated senescence could develop central and peripheral respiratory abnormalities. Adult male Senescence Accelerated Mouse Prone 8 (SAMP8) and the control SAMR1 mice (10 months old) were used. Ventilatory parameters were assessed by whole-body plethysmography, and measurements of respiratory input impedance were performed. SAMP8 mice exhibited a reduction in the density of neurokinin-1 receptor immunoreactivity in the entire ventral respiratory column. Physiological experiments showed that SAMP8 mice exhibited a decreased tachypneic response to hypoxia (FiO2 = 0.08; 10 min) or hypercapnia (FiCO2 = 0.07; 10 min). Additionally, the ventilatory response to hypercapnia increased further due to higher tidal volume. Measurements of respiratory mechanics in SAMP8 mice showed decreased static compliance (Cstat), inspiratory capacity (IC), resistance (Rn), and elastance (H) at different ages (3, 6, and 10 months old). SAMP8 mice also have a decrease in contractile response to methacholine compared to SAMR1. In conclusion, our findings indicate that SAMP8 mice display a loss of the NK1-expressing neurons in the respiratory brainstem centers, along with impairments in both central and peripheral respiratory mechanisms. These observations suggest a potential impact on breathing in a senescence animal model., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although there has been an increase in bench test evaluation of mechanical ventilators in recent years, a publication gap remains in assessing Pressure Control Continuous Mandatory Ventilation Modes with a set point targeting scheme PC-CMVs. This study evaluates the operational variability in PC-CMVs of eleven transport and emergency ventilators used in ICU units in Brazil during the COVID-19 pandemic. The assessment involved a comprehensive set of test scenarios derived from existing literature and the NBR ISO 80601-2-12:2014 standard. Nine parameters were computed for five consecutive breaths, offering a comprehensive characterization of pressure and flow waveforms. Most ventilators had Inspiratory pressure and PEEP values that fell outside of the tolerance ranges. Notably, three mechanical ventilators failed to reach the target pressures within the specified inspiratory times during test scenarios with a higher time constant (τ). We observed significant differences among emergency and transport ventilators in all assessed parameters, indicating a performance difference in PC-CMVs modes. The current results might help clinicians determine which ventilator models are suitable for specific clinical situations, particularly when unfavorable circumstances compel doctors to use ventilators that may not provide adequate support for patients in intensive care units., (© 2024. The Author(s).)

Background: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (F I O 2 ) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of F I O 2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV., Methods: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with F I O 2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces., Results: Following balloon occlusion, a steep decrease in left ROI-EELI with F I O 2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher F I O 2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher F I O 2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher F I O 2 ., Conclusions: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high F I O 2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place., Trial Registration: Not applicable., (© 2024. The Author(s).)

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co-release the agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARH AgRP/NPY neurons regulate several hypothalamic-pituitary-endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARH AgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARH AgRP/NPY neurons on the pattern of GH secretion in fed and food-deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARH AgRP/NPY neurons (AgRP ∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP ∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP ∆GHR mice. Our findings indicate that short-term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARH AgRP/NPY neurons., (© 2023 British Society for Neuroendocrinology.)

Background: Heart Failure with Preserved Ejection Fraction (HFpEF) is a syndrome characterized by different degrees of exercise intolerance, which leads to poor quality of life and prognosis. Recently, the European score (HFA-PEFF) was proposed to standardize the diagnosis of HFpEF. Even though Global Longitudinal Strain (GLS) is a component of HFA-PEFF, the role of other strain parameters, such as Mechanical Dispersion (MD), has yet to be studied. In this study, we aimed to compare MD and other features from the HFA-PEFF according to their association with exercise capacity in an outpatient population of subjects at risk or suspected HFpEF., Methods: This is a single-center cross-sectional study performed in an outpatient population of 144 subjects with a median age of 57 years, 58% females, referred to the Echocardiography and Cardiopulmonary Exercise Test to investigate HFpEF., Results: MD had a higher correlation to Peak VO2 (r=-0.43) when compared to GLS (r=-0.26), MD presented a significant correlation to Ventilatory Anaerobic Threshold (VAT) (r=-0.20; p = 0.04), while GLS showed no correlation (r=-0.14; p = 0.15). Neither MD nor GLS showed a correlation with the time to recover VO2 after exercise (T1/2). In Receiver Operator Characteristic (ROC) analysis, MD presented superior performance to GLS to predict Peak VO2 (AUC: 0.77 vs. 0.62), VAT (AUC: 0.61 vs. 0.57), and T1/2 (AUC: 0.64 vs. 0.57). Adding MD to HFA-PEFF improved the model performance (AUC from 0.77 to 0.81)., Conclusion: MD presented a higher association with Peak VO2 when compared to GLS and most features from the HFA-PEFF. Adding MD to the HFA-PEFF improved the model performance., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Lung physiology research advanced significantly over the last 100 years. Respiratory mechanics applied to animal models of lung disease extended the knowledge of the workings of respiratory system. In human research, a better understanding of respiratory mechanics has contributed to development of mechanical ventilators. In this review, we explore the use of respiratory mechanics in basic science to investigate asthma and chronic obstructive pulmonary disease (COPD). We also discuss the use of lung mechanics in clinical care and its role on the development of modern mechanical ventilators. Additionally, we analyse some bench-developed technologies that are not in widespread use in the present but can become part of the clinical arsenal in the future. Finally, we explore some of the difficult questions that intensive care doctors still face when managing respiratory failure. Bringing back these questions to bench can help to solve them. Interaction between basic and translational science and human subject investigation can be very rewarding, as in the conceptualization of "Lung Protective Ventilation" principles. We expect this interaction to expand further generating new treatments and managing strategies for patients with respiratory disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biselli, Degobbi Tenorio Quirino Dos Santos Lopes, Righetti, Moriya, Tibério and Martins.)

Background: During protective mechanical ventilation, electrical impedance tomography (EIT) is used to monitor alveolar recruitment maneuvers as well as the distribution of regional ventilation. This technique can infer atelectasis and lung overdistention during mechanical ventilation in anesthetized patients or in the ICU. Changes in lung tissue stretching are evaluated by monitoring the electrical impedance of lung tissue with each respiratory cycle., Objective: This study aimed to evaluate the distribution of regional ventilation during recruitment maneuvers based on the variables obtained in pulmonary electrical impedance tomography during protective mechanical ventilation, focusing on better lung recruitment associated with less or no overdistention., Methods: Prospective clinical study using seven adult client-owned healthy dogs, weighing 25 ± 6 kg, undergoing elective ovariohysterectomy or orchiectomy. The animals were anesthetized and ventilated in volume-controlled mode (7 ml.kg -1 ) with stepwise PEEP increases from 0 to 20 cmH 2 O in steps of 5 cmH 2 O every 5 min and then a stepwise decrease. EIT, respiratory mechanics, oxygenation, and hemodynamic variables were recorded for each PEEP step., Results: The results show that the regional compliance of the dependent lung significantly increased in the PEEP 10 cmH 2 O decrease step when compared with baseline ( p < 0.027), and for the nondependent lung, there was a decrease in compliance at PEEP 20 cmH 2 O ( p = 0.039) compared with baseline. A higher level of PEEP was associated with a significant increase in silent space of the nondependent regions from the PEEP 10 cmH 2 O increase step ( p = 0.048) until the PEEP 15 cmH 2 O (0.019) decrease step with the highest values at PEEP 20 cmH 2 0 ( p = 0.016), returning to baseline values thereafter. Silent space of the dependent regions did not show any significant changes. Drive pressure decreased significantly in the PEEP 10 and 5 cmH 2 O decrease steps ( p = 0.032) accompanied by increased respiratory static compliance in the same PEEP step ( p = 0.035 and 0.018, respectively)., Conclusions: The regional ventilation distribution assessed by EIT showed that the best PEEP value for recruitment maintenance, capable of decreasing areas of pulmonary atelectasis in dependent regions promoting less overinflation in nondependent areas, was from 10 to 5 cmH 2 O decreased steps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ambrósio, Sanchez, Pereira, Andrade, Rodrigues, Vitorasso, Moriya and Fantoni.)

Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable estimations of the respiratory impedance. In this work, we assessed the effects of removing the disrupted epoch when a 3-seconds input signal composed of one and a half 2-seconds full cycle is used., We tested our hypothesis in 25 SAMR1 mice under different levels of bronchoconstriction due to methacholine administration by iv bolus injections in different doses (15 animals) and by iv continuous infusion in different infusion rates (10 animals). Signal disruptions were computationally simulated as sharp drops in the pressure signal within a short timescale, and signal processing was performed using own developed algorithms., We found that the model goodness of fit worsens when averaging techniques to estimate the input respiratory impedance are not used. However, no statistically significant differences were observed in the comparison between Constant Phase Model parameters of the full 3-s signal and the 2-s non disrupted epoch in all doses or infusion rates for both methacholine delivery strategies., The proposed technique presents reliable outcomes that can reduce animal use in Forced Oscillation Technique realization.

Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in this study. The harmonic distortion index (k d ) was used to assess the respiratory system nonlinearity. The analysis of variance showed difference between groups (OVA vs control) and among doses for both protocols. Bolus protocol posttest: there was a difference between OVA and control at 0.3 and 1 mg/kg doses (p<0.0001 and p<0.001) for R n . Infusion: there was a difference between OVA and control at 192 μg.kg -1 .min -1 dose for R n , G and H, (p<0.01; p<0.001; p<0.001). An increment was found in k d values near to the observed peak values in bolus protocol. The bolus protocol could better differentiate inflamed and non-inflamed airway resistance, whereas the differences between OVA and control in continuous infusion protocol were associated to airway- and, mainly, parenchyma-related parameters. Moreover, the bolus protocol presented a higher nonlinear degree compared to the infusion protocol., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The desaturation-distance ratio (DDR), the ratio of the desaturation area to the distance walked, is a promising, reliable, and simple physiologic tool for functional evaluation in subjects with interstitial lung diseases. Lymphangioleiomyomatosis (LAM) is a rare neoplastic condition frequently associated with exercise impairment. However, DDR has rarely been evaluated in patients with LAM. Objectives: To assess DDR during maximal and submaximal exercises and evaluate whether DDR can be predicted using lung function parameters. Methods: A cross-sectional study was conducted in a cohort of women with LAM. The 6-min walking test (6MWT) and the incremental shuttle walking test (ISWT) were performed, and DDR was obtained from both tests. The functional parameters were assessed at rest using spirometry and body plethysmography. The pulmonary function variables predictive of DDR were also assessed. Results: Forty patients were included in this study. The mean age was 46 ± 10 years. Airway obstruction, reduced DL CO , and air trapping were found in 60, 57, and 15% of patients, respectively. The distance walked and the DDR for the 6MWT and ISWT were, respectively, 517 ± 65 and 443 ± 127 m; and 6.6 (3.8-10.9) and 8.3 (6.2-12.7). FEV 1 (airway obstruction) and reduced DL CO and RV/TLC (air trapping) were independent variables predictive of DDR during exercises field tests [DDR 6MWT = 18.66-(0.06 × FEV 1%pred )-(0.10 × DL CO%pred ) + (1.54 × air trapping), R adjust 2 = 0.43] and maximal [DDR ISWT = 18.84-(0.09 × FEV 1%pred )-(0.05 × DL CO%pred ) + (3.10 × air trapping), R adjust 2 = 0.33]. Conclusion: Our results demonstrated that DDR is a useful tool for functional evaluation during maximal and submaximal exercises in patients with LAM, and it can be predicted using airway obstruction, reduced DL CO , and air trapping., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Queiroz, da Silva, Amaral, Oliveira, Moriya, Carvalho, Baldi and Carvalho.)

Assessment of respiratory mechanics extends from basic research and animal modeling to clinical applications in humans. However, to employ the applications in human models, it is desirable and sometimes mandatory to study non-human animals first. To acquire further precise and controlled signals and parameters, the animals studied must be further distant from their spontaneous ventilation. The majority of respiratory mechanics studies use positive pressure ventilation to model the respiratory system. In this scenario, a few drug categories become relevant: anesthetics, muscle blockers, bronchoconstrictors, and bronchodilators. Hence, the main objective of this study is to briefly review and discuss each drug category, and the impact of a drug on the assessment of respiratory mechanics. Before and during the positive pressure ventilation, the experimental animal must be appropriately sedated and anesthetized. The sedation will lower the pain and distress of the studied animal and the plane of anesthesia will prevent the pain. With those drugs, a more controlled procedure is carried out; further, because many anesthetics depress the respiratory system activity, a minimum interference of the animal's respiration efforts are achieved. The latter phenomenon is related to muscle blockers, which aim to minimize respiratory artifacts that may interfere with forced oscillation techniques. Generally, the respiratory mechanics are studied under appropriate anesthesia and muscle blockage. The application of bronchoconstrictors is prevalent in respiratory mechanics studies. To verify the differences among studied groups, it is often necessary to challenge the respiratory system, for example, by pharmacologically inducing bronchoconstriction. However, the selected bronchoconstrictor, doses, and administration can affect the evaluation of respiratory mechanics. Although not prevalent, studies have applied bronchodilators to return (airway resistance) to the basal state after bronchoconstriction. The drug categories can influence the mathematical modeling of the respiratory system, systemic conditions, and respiratory mechanics outcomes.

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Subjects with severe and very severe chronic obstructive pulmonary disease (COPD) present thoracoabdominal asynchrony (TAA) that reduces ventilatory efficiency and exercise capacity. However, no therapeutic intervention has focused on reducing TAA. The purpose of this study was to evaluate the effects of elastic tape (ET) on thoracoabdominal mechanics, dyspnea symptoms, exercise capacity, and physical activity level in nonobese male subjects with severe-to-very severe COPD. This crossover, randomized trial included nonobese males with severe to very severe COPD. ET was placed on the chest wall and abdomen to reduce TAA. Subjects were evaluated at three hospital visits, each 7 days apart. At visit 1 , thoracoabdominal kinematic and pulmonary ventilation were evaluated by optoelectronic plethysmography and electrical impedance tomography, respectively, both at rest and during isoload exercise testing. At visit 2 , a cardiopulmonary exercise test (CPET; 10 W/min) was performed until exhaustion. Between the visits, subjects used a physical activity monitor (PAM) (at least 5 days of measurement; 10 h/day). At visit 3 , all the tests were repeated in the opposite order of the previous randomization. During the isoload exercise, subjects with ET presented lower tidal and minute volumes ( P = 0.01) and reduced TAA ( P = 0.02) and dyspnea ( P = 0.04). During the CPET, subjects with ET presented an increase in peak oxygen consumption (V̇o 2peak ; L/min and mL·kg -1 ·min -1 ; P = 0.01), test duration ( P = 0.009), and maximal load ( P = 0.03). Moderate and vigorous physical activity (MVPA), which was evaluated by the PAM, was also increased in subjects with ET ( P = 0.01). ET reduced TAA and dyspnea and increased exercise capacity and the duration of MVPA in nonobese male subjects with severe-to-very severe COPD NEW & NOTEWORTHY Elastic tape can be used as a new and low-cost intervention to reduce thoracoabdominal asynchrony and sedentary behavior as well as improve exercise capacity and physical activity level in nonobese male subjects with severe-to-very severe chronic obstructive pulmonary disease.

One of the possible causes of death in epilepsy is breathing disorders, especially apneas, which lead to an increase in CO 2 levels (hypercapnia) and/or a decrease in O 2 levels in arterial blood (hypoxemia). The respiratory neurons located in the ventral brainstem respiratory column are the main groups responsible for controlling breathing. Recent data from our group demonstrated respiratory changes in two experimental models of epilepsy, i.e. audiogenic epilepsy, and amygdala rapid kindling. Here, we aimed to evaluate respiratory changes in the classic model of temporal lobe epilepsy induced by intra-hippocampal injection of pilocarpine. Adult Wistar rats with stainless-steel cannulas implanted in the hippocampus region were used. The animals were submitted to pilocarpine injection (2.4 mg/μL, N = 12-15) or saline (N = 9) into the hippocampus. The respiratory parameters analyzed by whole-body plethysmography were respiratory rate (f R ), tidal volume (V T ) and ventilation (V E ). Respiratory mechanics such as Newtonian airway resistance (R n ), viscance of the pulmonary parenchyma (G) and the elastance of the pulmonary parenchyma (H) were also investigated. No changes in baseline breathing were detected 15 or 30 days after pilocarpine-induced status epilepticus (SE). However, 30 days after pilocarpine-induced SE, a significant reduction in V E was observed during hypercapnic (7% CO 2 ) stimulation, without affecting the hypoxia (8% O 2 ) ventilatory response. We also did not observe changes in respiratory mechanics. The present results suggest that the impairment of the hypercapnia ventilatory response in pilocarpine-induced SE could be related to a presumable degeneration of brainstem respiratory neurons but not to peripheral mechanisms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, cross-contamination risks, and aerosol dissemination. After the prototype development phase, preclinical bench-tests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures.

Mechanical evaluation of tracheal grafts is of great relevance for transplant research. Although there are some publications demonstrating different techniques of tracheal mechanical evaluation, there is still no definitive or preferred protocol available. Here, we present a simple image processing acquisition system that can be used for in vivo experiments. Six male Wistar rats were submitted to orotracheal intubation and a longitudinal incision was made to expose the trachea. Images of tracheae were acquired from a video camera in different scenarios of bronchoconstriction using methacholine (MCh) (Basal, PBS, MCh 30 μg/kg, MCh 300 μg/kg, and postmetabolized) during imposed-inspiration and imposed-expiration. The area variation ratio (the ratio between areas during expiration vs. inspiration) was 1.1× for the Basal group, while the ratio for MCh 300 µg/kg was 6.5×. The area variation of imaged tracheae was statistically significant at the dose of MCh 300 µg/kg for imposed-inspiration versus imposed-expiration (P = .002). Likewise, elastance data of respiratory mechanics indicated a statistically significant difference at the dose of MCh 300 µg/kg for imposed-inspiration versus imposed-expiration (P = .026). Our image processing analysis protocol presented corresponding behavior when compared to mechanical parameters of the respiratory system. In addition, our image acquisition system was able to highlight the differences between imposed-inspiration and imposed-expiration. Image analysis of the tracheal area variation seems to be in agreement with the elastance of the respiratory system. Taken together, these observations may help future studies of tracheal transplantation for in situ assessment of graft patency., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Impact Statement: Respiratory mechanics studies are associated with fundamental research and translational studies; the present work thus investigates this particular matter. Our current research describes differences and similarities between two different ways of administrating a very prevalent bronchoconstrictor (methacholine) in an aging process scenario. The core issue of our work is related with troubles we find with the bolus protocol and the application of the mathematical model used to assess the respiratory mechanics. Our findings reveal the continuous infusion as an alternative to these problems and we hope to provide the proper foundations to a more reliable assessment in the respiratory field.

Background: Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient-ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (V T ) at protective levels with NAVA and PSV in patients with ARDS., Methods: We conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and V T . Asynchrony events detection was based on waveform analysis., Results: We randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain V T below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, V T was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH 2 O) than in PSV (19 ± 3 cmH 2 O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0-2.7) in PSV and 0% (0-2.2) in NAVA (p = 0.6835)., Conclusions: It was feasible to keep V T in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar V T , RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation. Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258.

Aim: This study aimed to analyze the Constant Phase Model (CPM) Coefficient of Determination (COD) and an index of harmonic distortion ([Formula: see text]) behavior in intravenous methacholine dose response curve. We studied the COD and [Formula: see text] behavior of Control and Lung Inflammation (OVA) groups of mice and we proposed an alternative for moments when the CPM should not be applied. Methods: 9-week female BALB/c mice were studied, 8 of the control group (23.11 ± 1.27 g) and 11 of the lung inflammation group (OVA) (21.45 ± 2.16 g). The COD values were obtained during the respiratory mechanics assessment via Forced Oscillation Technique (FOT) and the [Formula: see text] was estimated a posteriori. Both control and OVA groups were submitted to 4 doses of Methacholine (MCh) protocol. Results: A strong correlation between COD and [Formula: see text] was present at the last two doses (0.3 mg/kg: r = -0.75, p  = 0.0013 and 1 mg/kg: r = -0.91; p  < 0.0001) in the OVA group. Differences were found in doses of 0.3 mg/kg between control and OVA for the maximum values of Rn (Newtonian Resistance) and G (tissue viscous); and between groups at PBS and doses of 0.03, 0.1 and 0.3 mg/kg for H (Elastance). A similar behavior was observed for the analysis of Area Under the Curve with the exclusion of the 3 first measurements of each dose. However, in this scenario, the comparison with the maximum value presented a higher discriminatory capacity of the parameters associated with the parenchyma. Conclusions: During severe bronchoconstriction there is a strong negative correlation between model goodness of fit and nonlinearities levels, reinforcing that COD is a robust acceptance criterion, whether still simple and easily obtained from the ventilator. We also pointed out the area under the CPM parameters dose response curve is a useful and can be used as a complementary analysis to peak comparison following bolus injections of methacholine.

Background: An oronasal mask is frequently used to treat OSA. In contrast to nasal CPAP, the effectiveness of oronasal CPAP varies by unknown mechanisms. We hypothesized that oral breathing and pressure transmission through the mouth compromises oronasal CPAP efficacy., Methods: Thirteen patients with OSA, well adapted to oronasal CPAP, were monitored by full polysomnography, pharyngeal pressure catheter, and nasoendoscope. Patients slept with low doses of midazolam, using an oronasal mask with sealed nasal and oral compartments. CPAP was titrated during administration by the oronasal and nasal routes, and was then reduced to induce stable flow limitation and abruptly switched to the alternate route. In addition, tape sealing the mouth was used to block pressure transmission to the oral cavity., Results: Best titrated CPAP was significantly higher by the oronasal route rather than the nasal route (P = .005), and patients with > 25% oral breathing (n = 5) failed to achieve stable breathing during oronasal CPAP. During stable flow limitation, inspiratory peak flow was lower, driving pressure was higher, upper airway inspiratory resistance was higher, and retropalatal and retroglossal area were smaller by the oronasal rather than nasal route (P < .05 for all comparisons). Differences were observed even among patients with no oral flow and were abolished when tape sealing the mouth was used (n = 6)., Conclusions: Oral breathing and transmission of positive pressure through the mouth compromise oronasal CPAP., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Oronasal breathing may adversely impact obstructive sleep apnea (OSA) patients either by increasing upper airway collapsibility or by influencing continuous positive airway pressure (CPAP) treatment outcomes. Predicting a preferential breathing route would be helpful to guide CPAP interface prescription. We hypothesized that anthropometric measurements but not self-reported oronasal breathing are predictors of objectively measured oronasal breathing. Seventeen OSA patients and nine healthy subjects underwent overnight polysomnography with an oronasal mask with two sealed compartments attached to independent pneumotacographs. Subjects answered questionnaires about nasal symptoms and perceived breathing route. Oronasal breathing was more common ( P = <0.001) among OSA patients than controls while awake (62 ± 44 vs. 5 ± 6%) and during sleep (59 ± 39 vs. 25 ± 21%, respectively). Oronasal breathing was associated with OSA severity ( P = 0.009), age ( P = 0.005), body mass index ( P = 0.044), and neck circumference ( P = 0.004). There was no agreement between objective measurement and self-reported breathing route among OSA patients while awake (κ = -0.12) and asleep (κ = -0.02). The breathing route remained unchanged after 92% of obstructive apneas. These results suggest that oronasal breathing is more common among OSA patients than controls during both wakefulness and sleep and is associated with OSA severity and anthropometric measures. Self-reporting is not a reliable predictor of oronasal breathing and should not be considered an indication for oronasal CPAP. NEW & NOTEWORTHY Continuous positive airway pressure (CPAP) interface choice for obstructive sleep apnea (OSA) patients is often guided by nasal symptoms and self-reported breathing route. We showed that oronasal breathing can be predicted by anthropometric measurements and OSA severity but not by self-reported oronasal breathing. Self-reported breathing and nasal symptoms should not be considered for CPAP interface choice.

Replacement of large tracheal defects remains an unmet clinical need. While recellularization of acellular tracheal grafts appeared to be a viable pathway, evidence from the clinic suggests otherwise. In hindsight, complete removal of chondrocytes and repopulation of the tracheal chondroid matrix to achieve functional tracheal cartilage may have been unrealistic. In contrast, the concept of a hybrid graft whereby the epithelium is removed and the immune-privileged cartilage is preserved is a radically different path with initial reports indicating potential clinical success. Here, we present a novel approach using a double-chamber bioreactor to de-epithelialize tracheal grafts and subsequently repopulate the grafts with exogenous cells. A 3 h treatment with sodium dodecyl sulfate perfused through the inner chamber efficiently removes the majority of the tracheal epithelium while the outer chamber, perfused with growth media, keeps most (68.6 ± 7.3%) of the chondrocyte population viable. De-epithelialized grafts support human bronchial epithelial cell (BEAS-2B) attachment, viability and growth over 7 days. While not without limitations, our approach suggests value in the ultimate use of a chimeric allograft with intact donor cartilage re-epithelialized with recipient-derived epithelium. By adopting a brief and partial decellularization approach, specifically removing the epithelium, we avoid the need for cartilage regeneration.

New Findings: What is the central question of this study? Clinical reports have described and suggested central and peripheral respiratory abnormalities in Parkinson's disease (PD) patients; however, these reports have never addressed the occurrence of these abnormalities in an animal model. What is the main finding and its importance? A mouse model of PD has reduced neurokinin-1 receptor immunoreactivity in the pre-Bӧtzinger complex and Phox2b-expressing neurons in the retrotrapezoid nucleus. The PD mouse has impairments of respiratory frequency and the hypercapnic ventilatory response. Lung collagen deposition and ribcage stiffness appear in PD mice., Abstract: Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by dopaminergic deficits in the brain. Parkinson's disease patients may experience shortness of breath, dyspnoea, breathing difficulties and pneumonia, which can be linked as a cause of morbidity and mortality of those patients. The aim of the present study was to clarify whether a mouse model of PD could develop central brainstem and lung respiratory abnormalities. Adult male C57BL/6 mice received bilateral injections of 6-hydroxydopamine (10 μg μl -1 ; 0.5 μl) or vehicle into the striatum. Ventilatory parameters were assessed in the 40 days after induction of PD, by whole-body plethysmography. In addition, measurements of respiratory input impedance (closed and opened thorax) were performed. 6-Hydroxydopamine reduced the number of tyrosine hydroxylase neurons in the substantia nigra pars compacta, the density of neurokinin-1 receptor immunoreactivity in the pre-Bӧtzinger complex and the number of Phox2b neurons in the retrotrapezoid nucleus. Physiological experiments revealed a reduction in resting respiratory frequency in PD animals, owing to an increase in expiratory time and a blunted hypercapnic ventilatory response. Measurements of respiratory input impedance showed that only PD animals with the thorax preserved had increased viscance, indicating that the ribcage could be stiff in this animal model of PD. Consistent with stiffened ribcage mechanics, abnormal collagen deposits in alveolar septa and airways were observed in PD animals. Our data showed that our mouse model of PD presented with neurodegeneration in respiratory brainstem centres and disruption of lung mechanical properties, suggesting that both central and peripheral deficiencies contribute to PD-related respiratory pathologies., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Work-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl 2 ) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl 2 exposure is 3 mg/ m 3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m 3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m 3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.

Tissue engineered (or bioengineered) tracheas are alternative options under investigation when the resection with end-to-end anastomosis cannot be performed. One approach to develop bioengineered tracheas is a complex process that involves the use of decellularized tissue scaffolds, followed by recellularization in custom-made tracheal bioreactors. Tracheas withstand pressure variations and their biomechanics are of great importance so that they do not collapse during respiration, although there has been no preferred method of mechanical assay of tracheas among several laboratories over the years. These methods have been performed in segments or whole tracheas and in different species of mammals. This article aims to present some methods used by different research laboratories to evaluate the mechanics of tracheal grafts and presents the importance of the tracheal biomechanics in both macro and micro scales. If bioengineered tracheas become a reality in hospitals in the next few years, the standardization of biomechanical parameters will be necessary for greater consistency of results before transplantations., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs., Methods: We conducted a crossover trial in the ICU of a university hospital in Brazil and included mechanically ventilated patients considered ready to undergo an SBT on the day of the study. Patients underwent two SBTs in randomized order: 30 min in PSV of 5 cmH 2 O or NAVA titrated to generate equivalent peak airway pressure (Paw), with a positive end-expiratory pressure of 5 cmH 2 O. The ICU team, blinded to ventilatory mode, evaluated whether patients passed each SBT. We captured flow, Paw and electrical activity of the diaphragm (EAdi) from the ventilator and used it to calculate respiratory rate (RR), tidal volume (VT), and EAdi. Detection of asynchrony events used waveform analysis and we calculated the asynchrony index as the number of asynchrony events divided by the number of neural cycles., Results: We included 20 patients in the study. All patients passed the SBT in PSV, and three failed the SBT in NAVA. Five patients were reintubated and the extubation failure rate was 25% (95% CI 9-49%). Respiratory parameters were similar in the two modes: VT = 6.1 (5.5-6.5) mL/Kg in NAVA vs. 5.5 (4.8-6.1) mL/Kg in PSV (p = 0.076) and RR = 27 (17-30) rpm in NAVA vs. 26 (20-30) rpm in PSV, p = 0.55. NAVA reduced AI, with a median of 11.5% (4.2-19.7) compared to 24.3% (6.3-34.3) in PSV (p = 0.033)., Conclusions: NAVA reduces patient-ventilator asynchrony index and generates a respiratory pattern similar to PSV during SBTs. Patients considered ready for mechanical ventilation liberation may be submitted to an SBT in NAVA using the same objective criteria used for SBTs in PSV., Trial Registration: ClinicalTrials.gov ( NCT01337271 ), registered April 12, 2011.

Purpose: Negative expiratory pressure (NEP) is a simple technique for the evaluation of upper airway collapsibility in patients with obstructive sleep apnea (OSA). Most studies evaluated NEP using a mouthpiece that may exclude the cephalic portion of the upper airway. We hypothesize that NEP determination is influenced by interface and position., Methods: We evaluated patients with suspected OSA using polysomnography, NEP (-5 cmH 2 O in sitting and supine position with mouthpiece and nasal mask). A subgroup also underwent computed tomography (CT) of the upper airway., Results: We studied a total of 86 subjects (72 male, age 46 ± 12 yrs, body mass index 30.0 ± 4.4 kg/m 2 , neck circumference 40.0 ± 3.5 cm, AHI 32.9 ± 26.4, range 0.5 to 122.5 events/hour). NEP was influenced by interface and position (p = 0.007), and upper airway was more collapsible with mouthpiece than with nasal mask in sitting position (p = 0.001). Position influenced NEP and was worse in supine only when evaluated by nasal mask. Expiratory resistance (R 0.2 ) at 0.2 s during NEP was significantly higher and independent of position with mouthpiece than with nasal mask (20.7 versus 8.6 cmH 2 O/L s -1 , respectively, p = 0.018). NEP evaluated with nasal mask in supine position and with mouthpiece in sitting position, but not when evaluated with mouthpiece in supine position, were correlated with upper airway anatomical measurements including tongue dimensions and pharyngeal length., Conclusions: Interface and position influence NEP. NEP evaluated with nasal mask in supine position may convey more relevant information for patients under investigation for OSA than when evaluated with mouthpiece.

Lung volume reduction surgery (LVRS) is an option for emphysematous patients who are awaiting lung transplantation. LVRS reduces nonfunctional portions of lung tissues and favors the compensatory lung growth (CLG) of the remaining lobes. This phenomenon diminishes dyspnea and improves both the respiratory mechanics and quality of life for the patients. An animal model of elastase-induced pulmonary emphysema was used to investigate the structural and functional lung response after LVRS. Bilobectomy was performed six weeks after elastase instillation. Two weeks after bilobectomy, CLG effects were evaluated by lung mechanics and histomorphometric analysis. After bilobectomy, the emphysematous animals presented decreased mean linear intercepts, increased elastic fiber proportion, and increased alveolar surface density, total volumes of airspace, tissue and respiratory region and absolute surface area. We conclude that bilobectomy promoted CLG in emphysematous animals, resulting in alveolar architecture repair.

Background: In patients with post-extubation respiratory distress, delayed reintubation may worsen clinical outcomes. Objective measures of extubation failure at the bedside are lacking, therefore clinical parameters are currently used to guide the need of reintubation. Electrical activity of the diaphragm (EAdi) provides clinicians with valuable, objective information about respiratory drive and could be used to monitor respiratory effort., Case Presentation: We describe the case of a patient with Chronic Obstructive Pulmonary Disease (COPD), from whom we recorded EAdi during four different ventilatory conditions: 1) invasive mechanical ventilation, 2) spontaneous breathing trial (SBT), 3) unassisted spontaneous breathing, and 4) Noninvasive Positive Pressure Ventilation (NPPV). The patient had been intubated due to an exacerbation of COPD, and after four days of mechanical ventilation, she passed the SBT and was extubated. Clinical signs of respiratory distress were present immediately after extubation, and EAdi increased compared to values obtained during mechanical ventilation. As we started NPPV, EAdi decreased substantially, indicating muscle unloading promoted by NPPV, and we used the EAdi signal to monitor respiratory effort during NPPV. Over the next three days, she was on NPPV for most of the time, with short periods of spontaneous breathing. EAdi remained considerably lower during NPPV than during spontaneous breathing, until the third day, when the difference was no longer clinically significant. She was then weaned from NPPV and discharged from the ICU a few days later., Conclusion: EAdi monitoring during NPPV provides an objective parameter of respiratory drive and respiratory muscle unloading and may be a useful tool to guide post-extubation ventilatory support. Clinical studies with continuous EAdi monitoring are necessary to clarify the meaning of its absolute values and changes over time.

Objective and approach: In this study, we estimated the constant phase model (CPM) parameters from the respiratory impedance of male BALB/c mice by performing the forced oscillation technique (FOT) in a control group (n  =  8) and in a murine model of asthma (OVA) (n  =  10). Then, we compared the results obtained by two different methods, using a commercial equipment (flexiVent-flexiWare 7.X; SCIREQ, Montreal, Canada) (FXV) and a wavetube method equipment (Sly et al 2003 J. Appl. Physiol. 94 1460-6) (WVT). We believe that the results from different methods may not be comparable. First, we compared the results performing a two-way analysis of variance (ANOVA) for the resistance, elastance and tissue damping., Main Results: We found statistically significant differences in all CPM parameters, except for resistance, when comparing Control and OVA groups. When comparing devices, we found statistically significant differences in resistance, while differences in elastance were not observed. For tissue damping, the results from WVT were observed to be higher than those from FXV. Finally, when comparing the relative variation between the CPM parameters of the Control and OVA groups in both devices, no significant differences were observed for all parameters., Significance: We then conclude that this assessment can compensate the effect of using different cannulas. Furthermore, tissue damping differences between groups can be compensated, since bronchoconstrictors were not used. Therefore, we believe that relative variations in the results between groups can be a comparing parameter when using different equipment without bronchoconstrictor administration.

Determining the presence of thoracoabdominal asynchrony in chronic obstructive pulmonary disease (COPD) patients is clinically relevant, but there is no consensus on the optimal parameters for performing this analysis. We assessed 22 COPD patients (FEV 1 40 ± 10% predicted) and 13 healthy controls during rest and exercise with optoelectronic plethysmography (70% maximum workload) on a cycle ergometer. Thoracoabdominal asynchrony was calculated by using phase angle and phase shift parameters following a three-compartment model involving the upper and lower rib cages and abdomen. Patients were classified as having thoracoabdominal asynchrony (TAA+) or not (TAA-) based on control values (mean ± 2 SDs). The chest wall volume and compartmental contribution were also measured. Thoracoabdominal asynchrony was observed in the lower rib cage. The phase angle detected more TAA+ patients at rest (15 vs. 7 patients) and during exercise (14 vs. 8 patients) compared with the phase shift. TAA+ patients also presented a lower chest wall volume, lower rib cage contribution, and higher abdominal contribution to chest wall volume compared with the control and TAA- patients. Thoracoabdominal asynchrony was more detectable during rest and exercise using the phase angle parameter, and it was observed in the lower rib cage compartment, reducing the chest wall volume during exercise in patients with COPD. NEW & NOTEWORTHY This study contributes to advance the knowledge over the previous lack of consensus on the assessment of thoracoabdominal asynchrony. We rigorously evaluated the related features that interfere in the measurement of the asynchrony (measurement tool, chest wall model and calculation parameter). Our results suggest that phase angle detects more suitably thoracoabdominal asynchrony that occurs on the lower ribcage and leads to a reduction in the chest wall volume during exercise in COPD patients., (Copyright © 2017 the American Physiological Society.)

Background: CPAP is the gold standard treatment for OSA and was conceived to be applied through a nasal interface. This study was designed to determine the acute effects of changing the nasal CPAP route to oronasal and oral in upper airway patency during sleep in patients with OSA. We hypothesized that the oronasal route may compromise CPAP's effectiveness in treating OSA., Methods: Eighteen patients (mean ± SD age, 44 ± 9 years; BMI, 33.8 ± 4.7 kg/m 2 ; apnea-hypopnea index, 49.0 ± 39.1 events/hour) slept with a customized oronasal mask with nasal and oral sealed compartments connected to a multidirectional valve. Sleep was monitored by using full polysomnography and induced by low doses of midazolam. Nasal CPAP was titrated up to holding pressure. Flow route was acutely changed to the oronasal (n = 18) and oral route (n = 16) during sleep. Retroglossal area was continuously observed by using nasoendoscopy., Results: Nasal CPAP (14.8 ± 4.1 cm H 2 O) was able to stabilize breathing in all patients. In contrast, CPAP delivered by the oronasal and oral routes promoted obstructive events in 12 (66.7%) and 14 (87.5%) patients, respectively. Compared with stable breathing during the nasal route, there was a significant and progressive reduction in the distance between the epiglottis and tongue base and the retroglossal area when CPAP was delivered by the oronasal and oral routes., Conclusions: CPAP delivered through the oronasal route may compromise CPAP's effectiveness in treating OSA., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic disease that may cause left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. Recent studies have shown a high prevalence of OSA among patients with HCM. Because the hemodynamics in patients with LVOT obstruction are unstable and depend on the loading conditions of the heart, we evaluated the acute effects of CPAP on hemodynamics and cardiac performance in patients with HCM., Methods: We studied 26 stable patients with HCM divided into nonobstructive HCM (n = 12) and obstructive HCM (n = 14) groups (LVOT gradient pressure lower or higher than 30 mm Hg, respectively). Patients in the supine position while awake were continuously monitored with beat-to-beat BP measurements and electrocardiography. Two-dimensional echocardiography was performed at rest (baseline) and after 20 min of nasal CPAP at 1.5 cm H 2 O and 10 cm H 2 O, which was applied in a random order interposed by 10 min without CPAP., Results: BP, cardiac output, stroke volume, heart rate, left ventricular ejection fraction, and LVOT gradient did not change during the study period in either group. CPAP at 10 cm H 2 O decreased right atrial size and right ventricular relaxation in all patients. It also decreased left atrial volume significantly and decreased right ventricular outflow acceleration time, suggesting an increase in pulmonary artery pressure in patients with obstructive HCM., Conclusions: The acute application of CPAP is apparently safe in patients with HCM, because CPAP does not lead to hemodynamic compromise. Long-term studies in patients with HCM and sleep apnea and nocturnal CPAP are warranted., Trial Registry: ClinicalTrials.gov; No. NCT01631006; URL: www.clinicaltrials.gov., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objectives: There is a growing interest to develop a simple method to characterize the mechanisms leading to upper airway collapse in order to guide treatment options in patients with obstructive sleep apnea (OSA). Critical closing pressure (Pcrit) during sleep is able to predict the anatomical component of OSA. However, Pcrit is a laborious method that is only used for research purposes. The application of negative expiratory pressure (NEP) is a simple method to assess upper airway collapsibility that can be easily performed during wakefulness. We hypothesized that NEP will be, similarly to Pcrit, associated with upper airway anatomy assessed by computed tomography (CT) scan., Methods: Patients under investigation for OSA underwent polysomnography, CT of the upper airway, NEP while awake, and Pcrit during sleep. NEP was performed with -5 cm H 2 O in supine position using a nasal mask. Pcrit was measured during sleep induced by low doses of midazolam., Results: Twenty-eight male subjects were studied (age 45 ± 13 y, body mass index 29.4 ± 4.9 kg/m 2 , apnea-hypopnea index (AHI) 30 ± 26, range 2 to 86 events/h). NEP and Pcrit were similarly associated with tongue area (r = 0.646 and r = 0.585), tongue volume (r = 0.565 and r = 0.613) and pharyngeal length (r = 0.580 and r = 0.611), respectively (p < 0.05 for all comparisons). NEP and Pcrit were also significantly correlated with AHI (r = 0.490 and r = 0.531). NEP and Pcrit were significantly higher in patients with severe OSA than the remaining population., Conclusions: NEP is a simple and promising method that is associated with the anatomical component of upper airway collapsibility. NEP may be valuable to select patients for noncontinuous positive airway pressure alternative therapies for OSA., (© 2016 American Academy of Sleep Medicine)

CPAP applied by a nasal mask is the gold standard treatment of obstructive sleep apnea. Oronasal masks are an alternative interface that can be used, especially in subjects with predominant oral breathing. However, oronasal masks have higher costs, are associated with larger leaks and higher residual apnea-hypopnea index, and in some cases may be ineffective., (© 2016 American Academy of Sleep Medicine.)

Background: OSA pathogenesis is complex and may vary according to ethnicity. The anatomic component predisposing to OSA is the result of the interaction between bony structure and upper airway soft tissues and can be assessed using passive critical closing pressure (Pcrit). We hypothesized that Japanese-Brazilians and whites present different predictors of upper airway collapsibility, suggesting different causal pathways to developing OSA in these two groups., Methods: Male Japanese-Brazilians (n = 39) and whites (n = 39) matched for age and OSA severity were evaluated by full polysomnography, Pcrit, and upper airway and abdomen CT scans for determination of upper airway anatomy and abdominal fat, respectively., Results: Pcrit was similar between the Japanese-Brazilians and the whites (-1.0 ± 3.3 cm H2O vs -0.4 ± 3.1 cm H2O, P = .325). The Japanese-Brazilians presented smaller upper airway bony dimensions (cranial base, maxillary, and mandibular lengths), whereas the whites presented larger upper airway soft tissue (tongue length and volume) and a greater imbalance between tongue and mandible (tongue/mandibular volume ratio). The cranial base angle was associated with Pcrit only among the Japanese-Brazilians (r = -0.535, P < .01). The tongue/mandibular volume ratio was associated with Pcrit only among the whites (r = 0.460, P < .01). Obesity-related variables (visceral fat, BMI, and neck and waist circumferences) showed a similar correlation with Pcrit in the Japanese-Brazilians and the whites., Conclusions: Japanese-Brazilians and whites present different predictors of upper airway collapsibility. Although craniofacial bony restriction influenced Pcrit only in the Japanese-Brazilians, an anatomic imbalance between tongue and mandible volume influenced Pcrit among the whites. These findings may have therapeutic implications regarding how to improve the anatomic predisposition to OSA across ethnicities., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified., Methods: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 μg/m3). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 μg/10 μL of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-γ) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2)., Results: DEP decreased IFN-γ levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p ≤ 0.001) and CD8+ T cells (p ≤ 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p ≤ 0.001), and the index D2 was statistically different (p = 0.038) from the control animals., Conclusion: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.

Study Objectives: Upper airway anatomy plays a major role in obstructive sleep apnea (OSA) pathogenesis. An inferiorly displaced hyoid as measured by the mandibular plane to hyoid distance (MPH) has been consistently associated with OSA. The hyoid is also a common landmark for pharyngeal length, upper airway volume, and tongue base. Tongue dimensions, pharyngeal length, and obesity are associated with OSA severity, although the link between these anatomical variables and pharyngeal collapsibility is less well known. We hypothesized that obesity as measured by body mass index (BMI), neck and waist circumferences, and variables associated with hyoid position (pharyngeal length, upper airway volume, and tongue dimensions) would be associated with passive pharyngeal critical closing pressure (Pcrit)., Design: Cross-sectional., Setting: Academic hospital., Patients: 34 Japanese-Brazilian males age 21 to 70 y., Interventions: N/A., Measurements and Results: We performed computed tomography scans of the upper airway, overnight polysomnography, and Pcrit measurements in all subjects. On average, subjects were overweight (BMI = 28 ± 4 kg/m(2)) and OSA was moderately severe (apnea-hypopnea index = 29 [13-51], range 1-90 events/h). Factor analysis identified two factors among the studied variables: obesity (extracted from BMI, neck and waist circumferences) and hyoid position (MPH, pharyngeal length, tongue length, tongue volume, and upper airway volume). Both obesity and hyoid position correlated with Pcrit (r = 0.470 and 0.630, respectively) (P < 0.01). In addition, tongue volume, tongue length, pharyngeal length, and MPH correlated with waist and neck circumferences (P < 0.05)., Conclusions: Pharyngeal critical closing pressure is associated with obesity and hyoid position. Tongue dimensions, pharyngeal length, and the mandibular plane to hyoid distance are associated with obesity variables. These findings provide novel insight into the potential factors mediating upper airway collapse in obstructive sleep apnea., (© 2014 Associated Professional Sleep Societies, LLC.)

Bronchial responsiveness during methacholine (MCh) challenge was analysed in an elastase-induced mouse model of emphysema to explore the magnitude of the response in this model. Swiss mice were intratracheally instilled with saline or elastase (0.3 or 0.6 U). Twenty days afterward, mechanical ventilation data were collected from the closed and opened thorax of baseline and MCh (vehicle, 50 and 100 mg/mL) challenged mice. The lungs were prepared for morphometric analysis. In the 0.6 U group, airway resistance (Raw) and tissue elastance (H) were decreased, and hysteresivity (η) was increased (closed thorax). MCh increased Raw, G and H in all groups, but this increase was attenuated in the elastase-induced emphysema groups, the largest attenuation was observed in the 0.6 U (closed thorax condition). Elastase increased hyperinflation of the alveoli, alveolar collapse and the Lm and reduced the normal area. MCh reduced respiratory mechanics in elastase-induced emphysema, and this reduction was modulated by the collapsed and/or hyperinflated areas, which increased the heterogeneity of the lungs., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate bronchoconstriction episodes. A potential correlation of formaldehyde (FA) inhalation and asthma has been observed; however, the exact role of FA remains controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA) sensitisation using a parameter of respiratory mechanics. The involvement of nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were OVA-sensitised and challenged 14 days later. Our data showed that previous FA exposure in allergic rats reduced bronchial responsiveness, respiratory resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs, while Indomethacin partially reversed all of the parameters studied. The L-NAME and Indomethacin treatments reduced leukotriene B₄ levels while they increased thromboxane B₂ and prostaglandin E₂. In conclusion, FA exposure prior to OVA sensitisation reduces the respiratory mechanics and the interaction of NO and PGE₂ may be representing a compensatory mechanism in order to protect the lung from bronchoconstriction effects., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We evaluated the effects of cigarette smoke (CS) on lung inflammation and remodeling in a model of ovalbumin (OVA)-sensitized and OVA-challenged mice. Male BALB/c mice were divided into 4 groups: non-sensitized and air-exposed (control); non-sensitized and exposed to cigarette smoke (CS), sensitized and air-exposed (OVA) (50 μg+OVA 1% 3 times/week for 3 weeks) and sensitized and cigarette smoke exposed mice (OVA+CS). IgE levels were not affected by CS exposure. The increases in total bronchoalveolar fluid cells in the OVA group were attenuated by co-exposure to CS, as were the changes in IL-4, IL-5, and eotaxin levels as well as tissue elastance (p<0.05). In contrast, only the OVA+CS group showed a significant increase in the protein expression of IFN-γ, VEGF, GM-CSF and collagen fiber content (p<0.05). In our study, exposure to cigarette smoke in OVA-challenged mice resulted in an attenuation of pulmonary inflammation but led to an increase in pulmonary remodeling and resulted in the dissociation of airway inflammation from lung remodeling., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of a diaphragmatic breathing training program (DBTP) on thoracoabdominal motion and functional capacity in patients with chronic obstructive pulmonary disease., Design: A prospective, randomized controlled trial., Setting: Academic medical center., Participants: Subjects (N=30; forced expiratory volume in 1s, 42%±13% predicted) were randomly allocated to either a training group (TG) or a control group (CG)., Interventions: Subjects in the TG completed a 4-week supervised DBTP (3 individualized weekly sessions), while those in the CG received their usual care., Main Outcome Measures: Effectiveness was assessed by amplitude of the rib cage to abdominal motion ratio (RC/ABD ratio) (primary outcome) and diaphragmatic mobility (secondary outcome). The RC/ABD ratio was measured using respiratory inductive plethysmography during voluntary diaphragmatic breathing and natural breathing. Diaphragmatic mobility was measured by ultrasonography. A 6-minute walk test and health-related quality of life were also evaluated., Results: Immediately after the 4-week DBTP, the TG showed a greater abdominal motion during natural breathing quantified by a reduction in the RC/ABD ratio when compared with the CG (F=8.66; P<.001). Abdominal motion during voluntary diaphragmatic breathing after the intervention was also greater in the TG than in the CG (F=4.11; P<.05). The TG showed greater diaphragmatic mobility after the 4-week DBTP than did the CG (F=15.08; P<.001). An improvement in the 6-minute walk test and in health-related quality of life was also observed in the TG., Conclusions: DBTP for patients with chronic obstructive pulmonary disease induced increased diaphragm participation during natural breathing, resulting in an improvement in functional capacity., (Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)