Higher Respiratory Resistance Research Articles

Long-term pulmonary and neurodevelopmental impairment in a fetal growth restriction rabbit model.

Fetal growth restriction (FGR) remains one of the main obstetrical problems worldwide, with consequences beyond perinatal life. Animal models with developmental and structural similarities to the human are essential to understand FGR long-term consequences and design novel therapeutic strategies aimed at preventing or ameliorating them. Herein, we described the long-term consequences of FGR in pulmonary function, structure, and gene expression, and characterized neurodevelopmental sequelae up to preadolescence in a rabbit model. FGR was induced at gestational day 25 by surgically reducing placental blood supply in one uterine horn, leaving the contralateral horn as internal control. Neonatal rabbits born near term were assigned to foster care in mixed groups until postnatal day (PND) 21. At that time, one group underwent pulmonary biomechanical testing followed by lung morphometry and gene expression analysis. A second group underwent longitudinal neurobehavioral assessment until PND 60 followed by brain harvesting for multiregional oligodendrocyte and microglia quantification. FGR was associated with impaired pulmonary function and lung development at PND 21. FGR rabbits had higher respiratory resistance and altered parenchymal biomechanical properties in the lungs. FGR lungs presented thicker alveolar septal walls and reduced alveolar space. Furthermore, the airway smooth muscle content was increased, and the tunica media of the intra-acinar pulmonary arteries was thicker. In addition, FGR was associated with anxiety-like behavior, impaired memory and attention, and lower oligodendrocyte proportion in the frontal cortex and white matter. In conclusion, we documented and characterized the detrimental pulmonary function and structural changes after FGR, independent of prematurity, and beyond the neonatal period for the first time in the rabbit model, and describe the oligodendrocyte alteration in pre-adolescent rabbit brains. This characterization will allow researchers to develop and test therapies to treat FGR and prevent its sequelae.

Self-sterilization and self-powered real-time respiratory monitoring of reusable masks engineered by bioinspired coatings

Surgical masks are crucial personal protective equipment to prevent and suppress the transmission of highly infectious viruses, especially suffered from some pandemic outbreaks. However, due to the lack of sterilization functions, the long-term reused masks become the hotbed of microorganisms and further cause additional damages to human health. Furthermore, it is desirable to endow multifunctionalities to the masks, such as self-powered real-time respiratory monitoring to forecast breath-related diseases. Although many efforts have been made towards those requirements, the complicated surface engineering process and involved extra weight of these mask still brought adverse effects in high respiratory resistance and poor wearing comfortability. In this work, we reported a facile fabrication strategy towards multifunctional masks based on the surface modification of melt-blown cloth by two kinds of bioinspired coatings. After sequentially performed mussel-inspired polydopamine coating and metal-phenolic network (Fe3+ and gallic acid) coatings, the obtained masks not only maintained the features of light, flexibility, breathability and filterability, but also realized the self-sterilization under the sunlight irradiation, thus allowing the facile reutilization for many times. Moreover, benefiting from the wet electricity generated by carboxyl group of gallic acid, the modified mask could effectively monitor the different respiratory status in real time. It was anticipated that this work can provide a new strategy towards the multifunctional integration of next-generation masks.

Design of a Low Respiratory Resistance Mask for COVID-19.

Observational evidence suggests that mask-wearing mitigates transmission of COVID-19; at the same time high respiratory resistance leads to an unwillingness to wear masks. This paper proposed a respiratory drive structure to reduce the air resistance of a mask. This structure provides different shapes during expiration and inspiration while focusing on filtering dust, bacteria, or viruses. Meanwhile, the assembled system on the mask can be disassembled and replaced. Then porous media simulation is used to verify the model effect. Experimental results of a new mask show that the ventilation resistance is reduced by 20%, and the bacterial filtration efficiency meets the requirements of YY 0469—2011.

A comparative study of asthma with airflow limitation and asthma-COPD overlap using the forced oscillation technique

The forced oscillation technique（FOT）, which requires breathing without forced action, is a useful tool that can measure respiratory impedance. We investigated the physiological differences between asthma with smoking-unrelated airflow limitation and asthma-chronic obstructive pulmonary disease（COPD）overlap（ACO）using the FOT. Among 275 patients with asthma who presented at the Showa University Hospital from April 2018 through March 2019, 211 were enrolled and assigned into the asthma（BA）, asthma with airflow limitation（AL）, or ACO groups. Respiratory impedance measured using the FOT were compared among the groups. There were no significant differences in spirometry data between the AL and the ACO group. The AL group had higher respiratory resistance at 5Hz（R5）, 20Hz（R20）, and reactance at 5Hz than the ACO group, but there was no significant difference in subtracting R20 from R5（R5-R20）. R5 and R20 were similar between the ACO and the BA groups, but R5-R20, resonant frequency（Fres）, and low-frequency reactance area were significantly higher in the ACO group than the BA group. Fres yielded the highest area under the curve（AUC）to identify airflow limitation, and R20 yielded the highest AUC to identify the ACO group among patients with airflow limitation. An analysis using the cut off value to identify airflow limitation and ACO detected 33 patients as having ACO, 17 of whom were diagnosed with ACO. R5 and R20 measured by FOT are higher in AL than in ACO despite no difference in spirometry data, and are not significantly different between BA and ACO. Therefore, FOT aids our understanding of the physiological characteristics and provides clues for the treatment in asthmatics with airflow limitation.

Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring.

It was previously demonstrated that non-allergen-sensitized rodents born to mothers exposed to a high-fat diet (HFD) spontaneously develop lower respiratory compliance and higher respiratory resistance. In the present study, we sought to determine if mice born to mothers consuming HFD would exhibit changes in inflammatory response and lung remodeling when subjected to ovalbumin (OVA) sensitization/challenge in adult life. Mice born to dams consuming either HFD or standard chow had increased bronchoalveolar lavage (BAL) levels of IL-1β, IL-4, IL-5, IL-10, IL-13, TNF-α and TGF-β1 after challenge with OVA. IL-4, IL-13, TNF-α and TGF-β1 levels were further increased in the offspring of HFD-fed mothers. Mice born to obese dams also had exacerbated values of leukocyte infiltration in lung parenchyma, eosinophil and neutrophil counts in BAL, mucus overproduction and collagen deposition. The programming induced by maternal obesity was accompanied by increased expression of miR-155 in peripheral-blood mononuclear cells and reduced miR-133b in trachea and lung tissue in adult life. Altogether, the present data support the unprecedented notion that the progeny of obese mice display exacerbated responses to sensitization/challenge with OVA, leading to the intensification of the morphological changes of lung remodeling. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression.

Physiological and morphological differences of airways between COPD and asthma\u2013COPD overlap

Overlap of asthma and COPD has attracted attention recently. We aimed to clarify physiological and morphological differences of the airways between COPD and asthma–COPD overlap (ACO). Respiratory resistance and reactance and three-dimensional computed tomography data were evaluated in 167 patients with COPD. Among them, 43 patients who fulfilled the diagnosis of asthma were defined as having ACO. Among 124 patients with COPD without ACO, 86 with a comparable smoking history and airflow limitation as those with ACO were selected using propensity score matching (matched COPD). The intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi were measured and adjusted by body surface area (BSA; Ai/BSA and WT/√BSA, respectively). Patients with ACO had higher respiratory resistance and reactance during tidal breathing, but a smaller gap between the inspiratory and expiratory phases, compared with matched patients with COPD. Patients with ACO had a greater WT/√BSA in third- to fourth-generation bronchi, smaller Ai/BSA in fifth- to sixth-generation bronchi, and less emphysematous changes than did matched patients with COPD. Even when patients with ACO and those with COPD have a comparable smoking history and fixed airflow limitation, they have different physiological and morphological features of the airways.

Factors Causing Post-Anesthetic High Respiratory Resistance in Patients Undergoing Transurethral Resection of Bladder Tumors.

BackgroundIn this study, we investigated the causes of high respiratory resistance that is observed after general anesthesia. We focused on respiratory resistance at 5 Hz (R5), which were measured preoperatively and postoperatively.MethodsOur prospective observational study enrolled 68 patients who underwent transurethral resection of bladder tumors from April to October 2015. Respiratory impedance was measured the day before surgery and immediately after general anesthesia. Participants were divided into 2 groups: Group L (postoperative R5 values < 4.0 cmH2O/L/sec; n = 33) and Group H (postoperative R5 values ≥ 4.0 cmH2O/L/sec; n = 35). Patient background, preoperative R5 values, endotracheal tube or subglottic devices, anaesthetic period, desflurane or sevoflurane, and endotracheal suctioning were compared.ResultsSignificant parameters were height, inhalation of desflurane, endotracheal suctioning, and preoperative R5 value. Logistic regression showed that endotracheal suctioning and a higher preoperative R5 level increased postoperative respiratory resistance (> 4 cmH2O/L/sec).ConclusionsThe endotracheal suctioning at the end of anesthesia influenced respiratory resistance more than use of the endotracheal tube and desflurane.

Forced oscillation technique as a predictor of FEV1 improvement in asthma

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting β2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5Hz (R5), as well as a difference between R5 and R20 (R5–R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment.

Correlation of end tidal and arterial carbon dioxide levels in critically ill neonates and children.

Sir, We read with great interest the study titled “Correlation of end tidal and arterial carbon dioxide levels in critically ill neonates and children” by Mehta et al.[1] We wish to highlight certain important issues. It is not clear how the sample size was calculated for this study to reach to a fruitful conclusion as this was probably not a pilot study. We believe that without a priori calculation of sample size, it would be really impossible to draw conclusions. We observed a major discrepancy regarding the number of patients being enrolled and excluded from the study as evident from the flow chart in Figure 1 of the article published. In the neonatal arm, authors have excluded 21 patients, whereas the sum of excluded patients is 24. From the data provided by you, the number of patients would be 63 instead of 66, which would change the statistics as reported. Similarly, in the infant and children arm, of 10 pairs that were excluded, the cause of exclusion of two pairs is missing. In the neonatal arm, there were eight newborns (12%) suffering from congenital heart disease with left to right shunt. A large surgical shunt size is related to stiffer lungs and a large heart is associated with a higher respiratory resistance. During mechanical ventilation of patients, the end-tidal CO2 may be an unreliable substitute for arterial CO2. Studies have found a relationship between a decreased pulmonary to systemic shunt ratio and an increased arterial to end-tidal CO2 difference. This may indicate that a reason for the unreliability of end-tidal CO2 is an impaired gas exchange partially due to pulmonary hypoperfusion.[2] In the neonatal group, 68% of newborns were on vasoactive therapy. It is well established that the vasopressors actually decrease the pulmonary blood flow (PBF), which would have an adverse effect on the PaCO2 and PEtCO2 relationship. Also, it would have been more appropriate if the authors could have shown the dosage of vasopressors in the presence of shock/chronic heart failure in the severe acute respiratory distress syndrome group as it would have a significant bearing on the PBF and thereby on the ventilation. In newborns, mainstream sampling of the exhaled gas to monitor the EtCO2 was used, which has a dead space of around 6 mL. It is noteworthy that the mean weight of the neonate arm is 2.1 kg only as mentioned. In all the patients, we presume that a low tidal volume approach would have been applied as the ventilation strategy. Thus, the dead space would account for almost 40–50% of the exhaled air being analyzed by a mainstream sampler. We feel that low flow side-stream sampling would have been a more appropriate sampling tool in the neonate arm of this study as the significant dead space would be a confounding factor with regard to the result of the study.[2,3,4,5,6,7] Almost all the limitations highlighted are independent variables known to disrupt the positive correlation between PaCO2 and EtCO2. Hence, in our opinion, it would not be rational to conclude strongly that increased severity of lung disease as defined by P/F ratio < 200 negatively affects EtCO2 values in all age groups.

The impact of shunt size on lung function in infants with univentricular heart physiology*

To assess the relationship that shunt size, blood gases, and radiologic findings has on respiratory function in infants with univentricular heart physiology. Cardiac catheter laboratory at Rikshospitalet University Hospital, Norway. Fifteen infants with univentricular heart physiology admitted for cardiac catheterization. Lung function was measured by a fixed-orifice differential pressure flow sensor and mainstream volumetric capnography in 15 infants with univentricular heart arrangements during routine invasive assessment before the bidirectional cavopulmonary connection. Blood gases were measured from the indwelling catheters. Chest radiographs were assessed for heart size and pulmonary vasculature. Shunt size was assessed angiographically. Respiratory compliance was reduced in patients with a large surgical systemic-pulmonary arterial shunt (r = -0.67, r = 0.45, p = 0.03). Respiratory resistance was higher with increased heart size (r = 0.72, r = 0.52, p = 0.004). There was no association between arterial and end-tidal CO2 values. The arterial to end-tidal CO2 difference had an inverse relationship with the pulmonary to systemic shunt ratio (r = -0.38, r = 0.14, p = 0.015). A large surgical shunt size is related to stiffer lungs and a large heart is associated with a higher respiratory resistance. During mechanical ventilation of patients with univentricular heart physiology the end-tidal CO2 may be an unreliable substitute for arterial CO2 before the bidirectional cavopulmonary connection. We found a relationship between a decreased pulmonary to systemic shunt ratio and an increased arterial to end-tidal CO2 difference. This may indicate that a reason for the unreliability of end-tidal CO2 is an impaired gas exchange partially due to pulmonary hypoperfusion.

The effect of doxapram-induced hyperventilation on respiratory mechanics in horses

To investigate the influence of increased respiratory frequency on respiratory mechanics in the horse, measurements were made in two groups of seven tracheostomised horses before and after the administration of doxapram. The horses in group I had normal base line values for respiratory mechanics, whereas the horses in group II had significantly lower values of dynamic compliance (Cdyn), higher respiratory resistance (R), and a higher total change in pleural pressure (ΔP). The administration of 0·3 mg kg −1 doxapram intravenously resulted in a significant increase in respiratory frequency (f R), R, ΔP, tidal volume (V T), and peak to peak respiratory flow (V̇), and a decrease in Cdyn in both groups of horses. The group II horses had significantly greater increases in R and ΔP than the horses in group I.

"Intrinsic" PEEP (PEEPi): role of expiratory muscles

In normal subjects breathing at rest, lung volume at end-expiration corresponds with the elastic equilibrium volume, or relaxation volume (Vr), of the respiratory system. If expiratory duration is not long enough, then inspiration may begin before the system has returned to Vr, such that end-expiratory lung volume is higher than Vr. This condition is named dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure (PEEPi), also called auto PEEP, corresponds to the elastic recoil of the lung at end-expiration [1, 2]. In the spontaneously breathing subject, this dynamic hyperinflation occurs mainly when the rate of lung emptying is decreased owing to high respiratory resistance or flow limitation. The highest degrees of dynamic hyperinflation are, thus, encountered in patients with airway diseases, particularly chronic obstructive pulmonary disease (COPD) patients. In the ventilated patient, external determinants may also induce dynamic pulmonary hyperinflation, or increase the magnitude of dynamic hyperinflation that was already present before the onset of mechanical ventilation. These additional external determinants include a preceding inflation volume that is too large, a time available for expiration that is reduced or a decreased rate of lung emptying owing to high resistance associated with the tube, the ventilator tubing or devices [3]. Dynamic pulmonary hyperinflation has important pathophysiological and therapeutic implications mainly in critical care medicine [3]. In particular, it implies that as the inspiratory muscles start to contract they must first offset the elastic recoil pressure of the system before inspiratory flow can begin and lung volume can increase. PEEPi associated with dynamic pulmonary hyperinflation thus corresponds to an inspiratory threshold load and is associated with an increased inspiratory work of breathing. This has led several investigators to give external PEEP or continuous positive airway pressure (CPAP) in the belief that this would unload the inspiratory muscles and, therefore, reduce the inspiratory work of breathing [4–6]. It must be stressed, however, that PEEPi and dynamic pulmonary hyperinflation are not always linked. In fact, alveolar pressure can also remain positive throughout expiration when the expiratory muscles contract [1, 5]. With respect to this, recent studies have shown that in many patients with stable but severe COPD [7] as well as in many mechanically ventilated patients [8, 9], expiration is a mechanically active process. These observations, thus, provide strong evidence that the active nature of expiration is an important determinant of PEEPi in such patients and, therefore, that the importance of dynamic pulmonary hyperinflation has been overestimated. Since a positive end-expiratory alveolar pressure resulting from an expiratory muscle contraction does not represent an inspiratory threshold load, the level of external PEEP that is needed in such patients must be significantly less than conventionally thought. The contribution of expiratory muscle contraction to the increase in end-expiratory alveolar pressure has to be taken into account when applying external PEEP or CPAP to offset PEEPi or these procedures might, in fact, result in enhanced pulmonary dynamic hyperinflation with further deleterious consequences [4, 10]. In this issue of the European Respiratory Journal, ZAKYNTHINOS and co-workers [11] report on a method for detecting expiratory muscle use and quantifying its contribution to PEEPi. The two points at issue in this and other studies [7–9] are:

Respiratory mechanics I

The ARDS is a clinical entity which from a mechanical point of view is characterized not only by a low respiratory compliance but also by a high respiratory resistance (R). In five ARDS patients we analyzed the changes in total R of the respiratory system (Rmax) and airway plus endotracheal tube R (Rmin) induced by changing the airflow (V) rate at constant tidal volume (VT) and total PEEP (PEEP plus autoPEEP). Patients were ventilated in volume controlled mode (VC) and VC with inverse ratio (VCIRV), both with constant insufflation flow. Signals of V, and airway pressure (Paw) were digitized (sampling frequency 200Hz) and acquired by an IBM 55SX computer in order to perform the following calculations: Rmax, Rmin, DR (Rmax-Rmin), static compliance (C). VT was obtained by digital integration of V. Rmin was corrected for the closing time of the inspiratory valve. Statistical analysis was performed with a two-way ANOVA. Results: V PEEPt Ti/Tt VT L/e cmH20 8 reL VC .76±.06 9.5±.4 34+.5 590±42 VCIRV .30+.02 8.4+.5 73+2 610±47 P= <.001 .15 <.001 .5