lung compliance
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2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Yajuan Wang ◽  
Huizhi Zhu ◽  
Jiabing Tong ◽  
Zegeng Li

Objectives. This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. Methods. Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance ( R L ) and dynamic lung compliance ( C dyn ) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. Conclusions. Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.


Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 10
Author(s):  
Daniel Puhr-Westerheide ◽  
Jakob Reich ◽  
Bastian O. Sabel ◽  
Wolfgang G. Kunz ◽  
Matthias P. Fabritius ◽  
...  

(1) Background: Respiratory insufficiency with acute respiratory distress syndrome (ARDS) and multi-organ dysfunction leads to high mortality in COVID-19 patients. In times of limited intensive care unit (ICU) resources, chest CTs became an important tool for the assessment of lung involvement and for patient triage despite uncertainties about the predictive diagnostic value. This study evaluated chest CT-based imaging parameters for their potential to predict in-hospital mortality compared to clinical scores. (2) Methods: 89 COVID-19 ICU ARDS patients requiring mechanical ventilation or continuous positive airway pressure mask ventilation were included in this single center retrospective study. AI-based lung injury assessment and measurements indicating pulmonary hypertension (PA-to-AA ratio) on admission CT, oxygenation indices, lung compliance and sequential organ failure assessment (SOFA) scores on ICU admission were assessed for their diagnostic performance to predict in-hospital mortality. (3) Results: CT severity scores and PA-to-AA ratios were not significantly associated with in-hospital mortality, whereas the SOFA score showed a significant association (p < 0.001). In ROC analysis, the SOFA score resulted in an area under the curve (AUC) for in-hospital mortality of 0.74 (95%-CI 0.63–0.85), whereas CT severity scores (0.53, 95%-CI 0.40–0.67) and PA-to-AA ratios (0.46, 95%-CI 0.34–0.58) did not yield sufficient AUCs. These results were consistent for the subgroup of more critically ill patients with moderate and severe ARDS on admission (oxygenation index <200, n = 53) with an AUC for SOFA score of 0.77 (95%-CI 0.64–0.89), compared to 0.55 (95%-CI 0.39–0.72) for CT severity scores and 0.51 (95%-CI 0.35–0.67) for PA-to-AA ratios. (4) Conclusions: Severe COVID-19 disease is not limited to lung (vessel) injury but leads to a multi-organ involvement. The findings of this study suggest that risk stratification should not solely be based on chest CT parameters but needs to include multi-organ failure assessment for COVID-19 ICU ARDS patients for optimized future patient management and resource allocation.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Fatemeh Eghtedari ◽  
Shahnaz Fooladi ◽  
Ali Mohammadian Erdi ◽  
Atefeh Shadman ◽  
Mahzad Yousefian

Background: The coronavirus disease 2019 (COVID-19) has a high prevalence and mortality worldwide. Thousands of patients with acute respiratory failure caused by COVID-19 are daily hospitalized in intensive care units (ICUs) around the world. Many of these patients require full mechanical respiratory support and long-term ventilator use. Using different ventilators and calculating important variables can be helpful in meeting therapeutic needs of patients. Objectives: The aim of present study was to investigate the effect of expiratory time constant (RCEXP) on the course of treatment and duration of mechanical ventilation in patients with acute respiratory failure hospitalized in ICU. Methods: The present cross-sectional study was conducted on 60 patients with acute respiratory failure who were hospitalized in the ICU and underwent mechanical ventilation due to COVID-19 in the first six months of 2020. The variables of RCEXP, lung compliance and lung resistance in all patients were recorded daily and analyzed. Then, based on clinical outcome, the patients were divided into two groups: the patients with wean outcome (N = 40) and those with death outcome (N = 20). Results: The mean ± SD of lung compliance in patients who were separated from ventilator and patients with death outcome were 74.73 (18.58) mL/cm H2O and 36.92 (10.56) mL/cm H2O, respectively, which was statistically significant (P = 0.001). The mean ± SD of lung resistance in patients who were separated from ventilator and patients with death outcome were calculated at 9.25 (4.62) and 14 (6.5), respectively, which was statistically significant (P = 0.015). Also, there was a statistically significant difference between the two groups in terms of mean ± SD of RCEXP (0.67 (0.23) vs. 0.49 (0.19), P = 0.010). Conclusions: According to the results of this study, there was a significant difference between high resistance, low compliance, RCEXP, and weaning success of intubation in patients hospitalized in the ICU.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260719
Author(s):  
Habtamu B. Derseh ◽  
Jason Q. D. Goodger ◽  
Jean-Pierre Y. Scheerlinck ◽  
Chrishan S. Samuel ◽  
Ian E. Woodrow ◽  
...  

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson’s Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound’s ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.


2021 ◽  
Vol 12 (3) ◽  
pp. 26-32
Author(s):  
Danyele Holanda da Silva ◽  
Tassiane Maria Alves Pereira ◽  
Janaína De Moraes Silva

Introduction: Cardiovascular Diseases (CVD) are the main cause of morbidity and mortality in developed and developing countries. According to World Health Organization estimates, 17.9 million people died of CVD in 2016, representing 31% of all global deaths. Material and Method: Integrative review carried out in the databases PubMed, SciELO, Lilacs and PEDro, based on the guiding question of the search: “what is the effect of respiratory techniques on the lung function of patients undergoing cardiac surgery?”, And crossing of the terms: breathing exercises AND preoperative AND cardiac surgery (all terms present in MEsh and DeCs) from May to June 2020. Results: 104 articles were found in the selected databases, 67 articles were excluded, 37 were selected for full reading, eight of which were part of this review. Discussion: The present integrative review aimed to analyze the effects of respiratory techniques on lung function in patients undergoing cardiac surgery. Patients undergoing a cardiac surgical procedure, mainly develop postoperative pulmonary dysfunction with significant reduction in lung volumes, impaired respiratory function, decreased lung compliance and increased respiratory work. Final Considerations: Respiratory techniques such as breathing exercises and / or respiratory muscle training employed in patients undergoing a cardiac surgical procedure, improve lung function, consequently improving respiratory muscle strength as a whole, also interfering in the reduction of post-respiratory complications. CRM in this population.Keywords: Cardiac surgery; Breathing Exercises; Preoperative.


Author(s):  
Buranee Yangthara ◽  
Visanu Kittiarpornpon ◽  
Pitiporn Siripattanapipong ◽  
Walaiporn Bowornkitiwong ◽  
Ratchada Kitsommart ◽  
...  

Background: Before the advent of antenatal steroids, early non-invasive respiratory support (NIV) and intratracheal surfactant, antenatal terbutaline was also used to improve lung compliance and reduce the incidence of respiratory distress syndrome (RDS). Objectives: To study the association between antenatal terbutaline and endotracheal intubation (ET) within the first 24 hours of life, RDS, bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH) in infants with gestational age (GA) of < 32 weeks. And to study the association between antenatal terbutaline, and ET or NIV within the first 24 hours of life, and RDS in infants with GA of 32 to 36 weeks. Method: A retrospective medical record review of preterm infants delivered at a single tertiary care center from October 2016 to December 2020. Multivariable logistic regression was used to explore the association between antenatal terbutaline and neonatal respiratory support. Result: 1,794 infants were included, 234 (13.0%) had GA < 32 weeks and 1,560 (86.9%) had GA 32 to 36 weeks. Antenatal terbutaline, corticosteroid, or both agents were administered in 561 (31.3%), 1,461 (81.4%), and 555 (30.9%), respectively. Antenatal terbutaline was significantly associated with a reduction in ET (adjusted odds ratio (aOR) = 0.40, 95% confident interval (CI) 0.19 to 0.82, p = 0.012) in infants of GA < 32 weeks, but not in infants with GA 32 to 36 weeks. Antenatal terbutaline was not associated with RDS or BPD, but was significantly associated with a reduction in grade III-IV IVH (aOR 0.11, CI 0.01 to 0.98; p = 0.048), in infants of GA < 32 weeks. Conclusion: In a state-of-the-art neonatal care setting, antenatal terbutaline was associated with a reduction in ET during the first 24 hours in infants of GA < 32 weeks. The use of antenatal terbutaline to improve acute neonatal respiratory outcomes merits reconsideration.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3807-3807
Author(s):  
Hiroyuki Muranushi ◽  
Takero Shindo ◽  
Huong Thi Ngo ◽  
Fumiaki Gochi ◽  
Akihiko Yoshizawa ◽  
...  

Abstract Introduction Despite clinical development of novel immunosuppressants, the prognosis of pulmonary graft-versus-host disease (pGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still poor. It is clinically classified into obstructive and constrictive subtypes, but its pathophysiology is not fully elucidated due to difficulty in collecting human lung specimens. We have shown that the MEK inhibitors that target the MAP kinase pathway suppress gastrointestinal and cutaneous GVHD in mice. Therefore, other kinase inhibitors may have potentials to suppress pGVHD. We here explored key molecules in pGVHD patients who underwent lung transplantation and verified the potency of dual inhibition of the MEK/ERK and PI3K/AKT pathways. Methods For human histopathological analysis, we reviewed 45 lung specimens from the allo-HSCT recipients who underwent lung transplantation at our institute for pGVHD from 2008 through 2018. Single-cell level imaging mass cytometry of human pGVHD specimens was performed to visualize interactions of lymphocytes and monocytes around bronchioles. As for a murine pGVHD model, eight-week-old B10.BR (H2K k) mice were pretreated with 240 mg/kg cyclophosphamide and 7 Gy total body irradiation, followed by infusion of C57BL/6J (H2K b) bone marrow cells and splenocytes. Vehicles, the MEK inhibitors trametinib (tra) 0.1 mg/kg/day, cobimetinib (cobi) 0.1 mg/kg/day, the PI3K inhibitor taselisib (tase) 5 mg/kg/day and tacrolimus (tac) 1 mg/kg were given from day 0 through 28. Evaluation was made at day 42 following transplant: primary endpoint was survival rate and secondary endpoints included development of bronchiolitis and values of airway resistance and lung compliance. Immunosuppressive effects of those reagents for human cells were evaluated in vitro: CSFE dilution of T cells stimulated with allogeneic dendritic cells; expression of CD23/CD69 on B cells activated with IL-4/CD40L; TNF-α production of monocytes stimulated with lipopolysaccharide. Results Three pathological findings characterize human pGVHD: bronchiolitis obliterans, lymphocyte infiltration and wall thickening of bronchioles; pleuroparenchymal fibroelastosis (PPFE), proliferation of subpleural elastic fibers; peribronchitis, macrophage aggregation around the bronchi. Most cases with PPFE had subpleural arteriovenous inflammation, and immunostaining revealed that B cells and macrophages were abundantly infiltrated around the bronchioles. These results indicated that suppressing B cells and macrophages may be crucial to prevent pGVHD through avoiding vascular inflammation and bronchiolitis. In the murine pGVHD, cobi but not tra/tac improved survival rate (vehicle 31%; cobi 62%, tra 7%, tac 10% at day 42; p &lt; 0.01). Cobi attenuated development of bronchiolitis, venulitis and peribronchial macrophage aggregation. Cobi improved respiratory functions, such as airway resistance (vehicle 1.65 ± 0.19, cobi 2.86 ± 0.75 cmH 2O.s/mL, p &lt; 0.001) and lung compliance (vehicle 13.14 ± 0.71 cobi 8.99 ± 1.08 μL/cmH 2O, p &lt; 0.05). Notably, T cell infiltration around bronchioles was inhibited by cobi and tra, but B cell infiltration was inhibited only by cobi. Whereas cobi inhibited phosphorylation of AKT, tra compensatory upregulated it. Cobi inhibited B cell activation more than tra (%CD23 +CD69 + B cells: 32.8% with cobi 1μM, 53.0% with tra 1μM, p &lt; 0.05). In addition, cobi suppressed TNF-α production by monocytes more strongly than tra (%TNF-α + monocytes: 53.1% with cobi 1μM vs 71.6% with tra 1μM, p &lt; 0.05). Dual inhibition of the MEK/ERK and PI3K/AKT pathways with combination of tra and tase strongly suppressed B cells in vitro, and improved survival rate compared with vehicle and monotherapy of tra or tase in mice (Figure). Finally, imaging mass cytometry of human pGVHD specimens revealed that lymphocytes around bronchioles and venules were positive for phospho-ERK1/2 and phospho-AKT. Conclusions pGVHD is associated with vascular inflammation and bronchiolitis in humans and mice. Furthermore, phosphorylation of ERK1/2 and AKT is upregulated in human pGVHD. Given that dual inhibition of MEK/ERK and PI3K/AKT signaling suppresses vascular inflammation and bronchiolitis thorough inhibition of B cells and monocytes in mice, this strategy may provide a novel treatment option against human pGVHD. Figure 1 Figure 1. Disclosures Takaori-Kondo: ONO PHARMACEUTICAL CO., LTD.: Research Funding; Bristol-Myers K.K.: Honoraria; Celgene: Research Funding.


2021 ◽  
Vol 12 ◽  
Author(s):  
Habtamu B. Derseh ◽  
Kopiyawaththage U. E. Perera ◽  
Sasika N. Vithana Dewage ◽  
Andrew Stent ◽  
Emmanuel Koumoundouros ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic lung disease characterized by excessive extracellular matrix (ECM) deposition in the parenchyma of the lung. Accompanying the fibrotic remodeling, dysregulated angiogenesis has been observed and implicated in the development and progression of pulmonary fibrosis. Copper is known to be required for key processes involved in fibrosis and angiogenesis. We therefore hypothesized that lowering bioavailable serum copper with tetrathiomolybdate could be of therapeutic value for treating pulmonary fibrosis. This study aimed to investigate the effect of tetrathiomolybdate on angiogenesis and fibrosis induced in sheep lung segments infused with bleomycin. Twenty sheep received two fortnightly infusions of either bleomycin (3U), or saline (control) into two spatially separate lung segments. A week after the final bleomycin/saline infusions, sheep were randomly assigned into two groups (n = 10 per group) and received twice-weekly intravenous administrations of either 50 mg tetrathiomolybdate, or sterile saline (vehicle control), for 6 weeks. Vascular density, expressed as the percentage of capillary area to the total area of parenchyma, was determined in lung tissue sections immuno-stained with antibodies against CD34 and collagen type IV. The degree of fibrosis was assessed by histopathology scoring of H&amp;E stained sections and collagen content using Masson’s trichrome staining. Lung compliance was measured via a wedged bronchoscope procedure prior to and 7 weeks following final bleomycin infusion. In this large animal model, we show that copper lowering by tetrathiomolybdate chelation attenuates both bleomycin-induced angiogenesis and pulmonary fibrosis. Moreover, tetrathiomolybdate treatment downregulates vascular endothelial growth factor (VEGF) expression, and improved lung function in bleomycin-induced pulmonary fibrosis. Tetrathiomolybdate also suppressed the accumulation of inflammatory cells in bronchoalveolar lavage fluid 2 weeks after bleomycin injury. The molecular mechanism(s) underpinning copper modulation of fibrotic pathways is an important area for future investigation, and it represents a potential therapeutic target for pulmonary fibrosis.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qing-Yuan Wang ◽  
Yu-Wei Ji ◽  
Li-Xin An ◽  
Lei Cao ◽  
Fu-Shan Xue

Abstract Background The incidence of postoperative pulmonary complications (PPCs) is higher in obese patients undergoing general anesthesia and mechanical ventilation due to the reduction of oxygen reserve, functional residual capacity, and lung compliance. Individualized positive end-expiratory pressure (iPEEP) along with other lung-protective strategies is effective in alleviating postoperative atelectasis. Here, we compared the best static lung compliance (Cstat) titration of iPEEP with electrical impedance tomography (EIT) titration to observe their effects on postoperative atelectasis in obese patients undergoing laparoscopic surgery. Methods A total number of 140 obese patients with BMI ≥ 32.5kg/m2 undergoing elective laparoscopic gastric volume reduction and at moderate to high risk of developing PPCs will be enrolled and randomized into the optimal static lung compliance-directed iPEEP group and EIT titration iPEEP group. The primary endpoint will be pulmonary atelectasis measured and calculated by EIT immediately after extubation and 2 h after surgery. Secondary endpoints will be intraoperative oxygenation index, organ dysfunction, incidence of PPCs, hospital expenses, and length of hospital stay. Discussion Many iPEEP titration methods effective for normal weight patients may not be appropriate for obese patients. Although EIT-guided iPEEP titration is effective in obese patients, its high price and complexity limit its application in many clinical facilities. This trial will test the efficacy of iPEEP via the optimal static lung compliance-guided titration procedure by comparing it with EIT-guided PEEP titration. The results of this trial will provide a feasible and convenient method for anesthesiologists to set individualized PEEP for obese patients during laparoscopic surgery. Trial registration ClinicalTrials.govChiCTR2000039144. Registered on October 19, 2020


2021 ◽  
Author(s):  
Tommaso Mauri ◽  
Elena Spinelli ◽  
Bertrand Pavlovsky ◽  
Domenico Luca Grieco ◽  
Irene Ottaviani ◽  
...  

Background Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. Methods Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. Results Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = –0.735, P &lt; 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P &lt; 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P &lt; 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. Conclusions Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


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