Acute Airway Research Articles

PIN23 Costs-Consequences Analysis of Ceftaroline Fosamil for the Treatment of Community-Acquired Pneumonia in the Brazilian Private Healthcare System

Community-acquired pneumonia (CAP) is one of the most common infectious diseases and one of the leading causes of morbidity and mortality worldwide. It is defined as an acute lower airway infection, caused by viruses, fungi or bacteria, which develops in patients not exposed to hospital settings or health facilities. Therefore, the choice of initial antibiotic therapy is pivotal to achieve early response and possibly early discharge, and thus reducing hospital expenditure. Considering this scenario were developed a cost–consequence for ceftaroline fosamil in the perspective of Brazilian private healthcare system (BPHS). A decision tree model simulates a hypothetical cohort of 100 adult patients hospitalized to treat moderate to severe CAP, comparing two arms: the first consider ceftaroline fosamil while the second consider alternatives classically recommended for CAP by the Brazilian Society of Pulmonology and Tisiology - ceftriaxone and levofloxacin. The model results consider the transitions of those patients depending on the clinical response to the initial therapy. Where also measured all direct costs according with the consequences of the treatments in the perspective of BPHS. The analysis demonstrated that the use of ceftaroline fosamil as initial antibiotic treatment versus the comparators for CAP treatment may represent a significant reduction in total treatment cost, mainly due to the reduction in length of stay. It is important to note that this cost reduction was sufficient to offset the higher cost of acquiring ceftaroline fosamil as the initial antibiotic therapy. Cost-savings ranged from BRL 174,675 when compared to ceftriaxone, to BRL 5720,221 when compared to levofloxacin. Ceftaroline fosamil demonstrated potential as an initial antibiotic therapy when compared to alternative therapies for patients with moderate to severe CAP, as it can result in an increase in early response and a decrease in total costs for the BPHS.

Role for Mucin-5AC in Upper and Lower Airway Pathogenesis in Mice.

Mucin-5AC (MUC5AC) is a major secreted mucin in pathogenic airways. To determine its role in mucus-related airway disorders, Muc5ac-deficient (Muc5ac-/-) and wild-type (Muc5ac+/+) mice were compared in bleomycin-induced pulmonary fibrosis, respiratory syncytial virus (RSV) disease, and ozone toxicity. Significantly greater inflammation and fibrosis by bleomycin were developed in Muc5ac-/- lungs compared to Muc5ac+/+ lungs. More severe mucous cell metaplasia in fibrotic Muc5ac-/- lungs coincided with bronchial Muc2, Muc4, and Muc5b overexpression. Airway RSV replication was higher in Muc5ac-/- than in Muc5ac+/+ during early infection. RSV-caused pulmonary epithelial death, bronchial smooth muscle thickening, and syncytia formation were more severe in Muc5ac-/- compared to Muc5ac+/+. Nasal septal damage and subepithelial mucoserous gland enrichment by RSV were greater in Muc5ac-/- than in Muc5ac+/+. Ozone exposure developed more severe nasal airway injury accompanying submucosal gland hyperplasia and pulmonary proliferation in Muc5ac-/- than in Muc5ac+/+. Ozone caused periodic acid-Schiff-positive secretion only in Muc5ac-/- nasal airways. Lung E-cadherin level was relatively lower in Muc5ac-/- than in Muc5ac+/+ basally and after bleomycin, RSV, and ozone exposure. Results indicate that MUC5AC is an essential mucosal component in acute phase airway injury protection. Subepithelial gland hyperplasia and adaptive increase of other epithelial mucins may compensate airway defense in Muc5ac-/- mice.

A Case Report: Probably Concurrent Nasogastric Tube Syndrome and Cerebrovascular Disease in a Postoperative Patient

Nasogastric tube syndrome (NTS) is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. Although NTS is a rare cause of vocal cord paralysis, it has the potential of causing serious morbidities even mortality. We here with present a case of concurrent NTS and cerebrovascular disease patient. 73 year-old male was admitted to our university hospital emergency department with acute respiratory distress and stridor days after his cholecystectomy operation and laryngoscopy showed bilateral vocal cord paralysis. The patient was admitted to the intensive care unit (ICU) and urgent tracheotomy was performed. On the day after his discharge from the hospital, his vocal cord movements fully recovered state. Nasogastric tube syndrome can be considered in patient who complains because of acute upper airway obstruction with nasogastric tube inserted. Thinking NTS early may be reducing the complication rate.

Cyp19a1 is essential for macrophage function and pulmonary tissue repair following airway epithelial injury

CYP19A1 (the aromatase) is a key enzyme in the biosynthesis of estrogens, which have important regulatory functions, including roles as a major mitogenic stimulus for cellular proliferation. Using a new myeloid cell-specific Cyp19a1-null (Cyp19a1-null) mouse model, we tested the role of macrophage CYP19A1 in pulmonary regenerative response to naphthalene-induced bronchiolar epithelial cell injury. Wild-type and Cyp19a1-null mice were treated with naphthalene (200 mg/kg, IP) to induce acute lung injury, or with corn oil as a vehicle control. Mouse lung was examined at 24 hour, 72 hours, or 14 days after the treatment, for extent of acute airway injury, post-injury cellular proliferation, and tissue repair, respectively. At 24 hours, a genotype difference in the extent of naphthalene-induced airway injury was not detected. At 72 hours, the fraction of airway epithelial cells that are positive for the cell proliferation marker Ki67 was higher in naphthalene-treated wild-type mice (40%-70%) than in naphthalene-treated Cyp19a1-null mice (20-30%); whereas the fraction was much lower in corn oil treated control mice (3-5%). At 14 days, the bronchiolar epithelium was recovered to a greater extent in wild-type (~80%) than in the Cyp19a1-null mice (<30%), as indicated by the abundance of Club cells (positive for Club cell secretary protein) in the airway epithelium. Further studies of isolated macrophages indicated that Cyp19a1-null macrophages had reduced phagocytosis (by ~70%) and migration (by ~50%) activities, compared to wild-type controls. Thus, the loss of macrophage CYP19A1negativelyimpacted macrophage function and impeded the post-injury cellular proliferation and tissue repair in the lung airways.

Respiratory syncytial virus-induced high mobility group box 1 secretion modulates innate immune response to promote inflammation

Abstract Respiratory syncytial virus (RSV) is the single most common human pathogen responsible for ~ 60% of all acute lower respiratory tract infections in young children, and is a major cause of severe respiratory morbidity and mortality in the elderly, and the immunocompromised. Yet, no vaccine or efficacious treatment is available. Although the mechanisms of RSV-induced acute airway disease are not fully understood, lung inflammatory and immune events are key. Our studies show that RSV induces increased extracellular secretion of high-mobility group box 1 (HMGB1), a prominent damage-associated molecular pattern family member that alerts the immune system to potential damage and trigger immediate response. The goal of this study is to investigate the molecular mechanisms of RSV-induced HMGB1 release in the activation of innate immune response in promoting lung inflammation. Studies were conducted in BALB/c mice as well as human lung epithelial cells including A549 and normal small alveolar epithelial cells. To determine the role of HMGB1 in the activation of innate immune signaling, BALB/c mice and airway epithelial cells were infected with RSV in the presence or absence of recombinant HMGB1 or HMGB1 monoclonal antibody and measured RIG-I-dependent interferon-mediated innate antiviral immune response. Our studies demonstrated an important role of HMGB1 in cellular protection and the activation of innate immune signaling cascades to promote inflammation. Our studies indicate that HMGB1 acts as a signaling molecule to induce an increased inflammatory response in the lung, thus contributing to RSV pathogenesis. Modulation of proinflammatory function of HMGB1 may attenuate RSV-induced lung inflammation.

Exploratory research on asthma exacerbation risk factors using the Japanese claims database and machine learning: a retrospective cohort study

Objective: Analytical studies of risk factor assessment using machine learning have recently been reported. We performed an exploratory detection study of asthma exacerbation-related factors using health insurance claims data and machine learning to explore risk factors that have high generalizability and can be easily obtained in daily practice. Methods: A dataset of asthma patients during May 2014-April 2019 from the Japanese insurance claims database, MediScope® (DB) was used. Patient characteristics and disease information were extracted, and association with occurrence of asthma exacerbation was evaluated to comprehensively search for exacerbation risk factors. Asthma exacerbations were defined as the co-occurrence of emergency medical procedures, such as emergency transport and intravenous steroid injections, with asthma claims, which were recorded in the database. Results: In total, 5,844 (13.7%) subjects had exacerbations in 42,685 eligible cases from the DB. Information on approximately 3,300 diseases was subjected to a machine learning, and 25 variables were extracted as variable importance and targeted for risk assessment. As a result, sex, days without exacerbation from cohort entry date at look-back period, Charlson Comorbidity Index, allergic rhinitis, chronic sinusitis, acute airway disease (upper airway), acute airway disease (lower airways), Chronic obstructive pulmonary disease/chronic bronchitis, gastroesophageal reflux disease, and hypertension were significantly associated with exacerbation. Dyslipidemia and periodontitis were detected as associated factors of reduced exacerbation risk. Conclusions: A comprehensive analysis of claims data using machine learning showed asthma exacerbation risk factors mostly consistent with those in previous studies. Further examination in other fields is warranted. Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.1923740 .

A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice.

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA­challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

A Pediatric Emergency Medicine Refresher Course for Generalist Healthcare Providers in Belize: Respiratory Emergencies.

This is a refresher curriculum utilizing multiple methods of education to augment the skills of generalist healthcare providers in low- and middle-income countries (LMICs) in the identification and stabilization of pediatric respiratory emergencies. Our audience of implementation was Belizean generalist providers. Nine hours. In the pediatric population, early recognition and stabilization can improve patient outcomes. Compared with many Western systems that rely on specialists and even subspecialists, in many lower-resource settings, generalists provide most emergency medical care. The purpose of this module is to present a curriculum focused on the identification and stabilization of common pediatric respiratory emergencies for general practitioners (physicians and nurses) working in the acute care setting. Our aim is to provide a care framework and refresher training for the management of pediatric respiratory emergencies for providers who may regularly see the acutely ill pediatric patient but who may not have had recent or any extensive teaching in the management of acute pediatric airway management, bronchiolitis, pneumonia, and asthma. This curriculum presents a refresher course in recognizing and stabilizing pediatric acute respiratory complaints for generalist healthcare providers practicing in LMICs. Our goal is to implement this curriculum in the small LMIC of Belize. This module focuses on common respiratory complaints, including asthma, bronchiolitis, pneumonia and acute airway management. The educational strategies used in this curriculum include didactic lectures, medical simulation, small-group sessions, and a skills lab. We scored written pretests before and posttests after intervention and retested participants to evaluate for knowledge retention. Participants provided qualitative feedback on the module. We taught 26 providers. Twenty-one providers completed the posttest and eight completed the retest. The mean test scores improved from 8.3 ± 2.8 in the pretest to 9.7 ± 1.3 to the posttest (mean difference = 1.4; P = 0.027). The mean test score at pretest was 8.0 ± 4.0, which increased to 9.9 ± 2.5 at retest four months later (mean difference = 1.9, P = 0.049). Fifteen (71.4%) participants found the course "extremely useful," and 28 (28.5%) participants "very useful." This curriculum is an effective and well-received training tool for Belizean generalist providers. Although limited by sample size and 20% attrition for the retest, there was a statistically significant improvement in test performance. We believe that our pilot in Belize shows that this type of refresher course could be useful for teaching generalist providers in LMICs to optimize care of the acutely ill pediatric patient with respiratory ailment. Evaluation of other modules in this curriculum, application of the curriculum in other locations, and measuring clinical patient outcomes will be included in future investigations. Medical simulation, rapid cycle deliberate practice (RCDP), Belize, bronchiolitis, pneumonia, asthma, airway, respiratory distress, low- and middle-income country (LMIC), collaboration, global health.

Negative-pressure-related diffuse alveolar hemorrhage after monitored anesthesia care for vertebroplasty: a case report

BackgroundDiffuse alveolar hemorrhage (DAH) is a rare, life-threatening condition that can present as a spectrum of nonspecific symptoms, ranging from cough, dyspnea, and hemoptysis to severe hypoxemic respiratory failure. Perioperative DAH is frequently caused by negative pressure pulmonary edema resulting from acute airway obstruction, such as laryngospasm, although hemorrhage itself is rare.Case presentationThis case report describes an unexpected hemoptysis following monitored anesthesia care for vertebroplasty. A 68-year-old Asian woman, with a compression fracture of the third lumbar vertebra was admitted for vertebroplasty. There were no noticeable events during the procedure. After the procedure, the patient was transferred to the postanesthesia care unit (PACU), at which sudden hemoptysis occurred. The suspected airway obstruction may have developed during transfer or immediate arrive in PACU. In postoperative chest x-ray, newly formed perihilar consolidation observed in both lung fields. The patients was transferred to a tertiary medical institution for further evaluation. She diagnosed with DAH for hemoptysis, new pulmonary infiltrates on chest x-ray and anemia. The patient received supportive care and discharged without further events.ConclusionsShort duration of airway obstruction may cause DAH, it should be considered in the differential diagnosis of postoperative hemoptysis of unknown etiology.

Effectiveness of chest physiotherapy using passive slow expiratory techniques in dogs with airway fluid accumulation: A randomized controlled trial.

BackgroundProlonged slow expiration (PSE) and assisted cough (AC) are airway clearance techniques feasible and well tolerated in dogs.ObjectivesTo evaluate the effectiveness of PSE and AC as chest physiotherapy (CP) techniques in dogs with airway fluid accumulation.AnimalsThirty‐one client‐owned dogs hospitalized in an intensive care unit from October 2014 to May 2018.MethodsProspective randomized controlled trial. Dogs presented with or developing acute dyspnea during hospitalization associated with airway fluid accumulation were assigned to CP group (medical treatment and CP, 15 dogs) or control group (medical treatment alone, 16 dogs). The arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio (P/F ratio; PaO2/FiO2 × 100) was calculated daily for the 1st 48 hours of hospitalization and using the last arterial blood gas performed before discharge or death. The ratio of days of hospitalization with oxygen/total number of hospitalization days (ratio of oxygen‐free‐days [O2Free]) was calculated.ResultsDuring the 1st 48 hours, the P/F ratio increased significantly in the CP group compared to the control group (+ 35.1 mm Hg/day; 95% confidence interval [CI] = 0.4‐57.5; P = .03). The (median; 1st quartile to 3rd quartile) difference between the P/F ratio at discharge and inclusion was significantly higher in the CP group (178 mm Hg; 123‐241) than in the control group (54 mm Hg; −19 ‐ 109; P = .001). Mean O2Free increased by 46.4% in the CP group compared with control group (95% CI = 16‐59; P = .001). Mortality was 13% (2/15) in the CP group and 44% (7/16) in the control group (P = .07).Conclusions and Clinical ImportanceProlonged slow expiration and AC improved P/F ratio within 48 hours and decreased need for oxygenation in dyspneic dogs with acute airway fluid accumulation.

IRAK-M knockout promotes allergic airway inflammation, but not airway hyperresponsiveness, in house dust mite-induced experimental asthma model.

BackgroundIL-1 receptor associated-kinase (IRAK)-M, expressed by airway epithelium and macrophages, was shown to regulate acute and chronic airway inflammation exhibiting a biphasic response in an OVA-based animal model. House dust mite (HDM) is a common real-life aeroallergen highly relevant to asthma pathogenesis. The role of IRAK-M in HDM-induced asthma remains unknown. This study was aimed to investigate the effect of IRAK-M on allergic airway inflammation induced by HDM using IRAK-M knockout (KO) mice and the potential underlying mechanisms.MethodsIRAK-M KO and wild-type (WT) mice were sensitized and challenged with HDM. The differences in airway inflammation were evaluated 24 hours after the last challenge between the two genotypes of mice using a number of cellular and molecular biological techniques. In vitro mechanistic investigation was also involved.ResultsLung expression of IRAK-M was significantly upregulated by HDM in the WT mice. Compared with the WT controls, HDM-treated IRAK-M KO mice showed exacerbated infiltration of inflammatory cells, particularly Th2 cells, in the airways and mucus overproduction, higher epithelial mediators IL-25, IL-33 and TSLP and Th2 cytokines in bronchoalveolar lavage (BAL) fluid. Lung IRAK-M KO macrophages expressed higher percentage of costimulatory molecules OX40L and CD 80 and exhibited enhanced antigen uptake. However, IRAK-M KO didn’t impact the airway hyperreactivity (AHR) indirectly induced by HDM.ConclusionsThe findings indicate that IRAK-M protects allergic airway inflammation, not AHR, by modifying activation and antigen uptake of lung macrophages following HDM stimulation. Optimal regulation of IRAK-M might indicate an intriguing therapeutic avenue for allergic airway inflammation.

Physiological Effects of High-Flow Nasal Cannula Therapy and Its Use in Acute Cardiogenic Pulmonary Edema.

High-flow nasal cannula (HFNC) is an open oxygen delivery system, which provides heated and humidified oxygen at a high flow (up to 60 L/min). This effect can improve mucociliary function, airway clearance, and level of comfort to the patient. It can provide controlled and adequate fraction of inspired oxygen (FiO2) between 21% and 100%. Generation of end-expiratory pressure helps in carbon dioxide washout, reduction of anatomical dead space, and recruitment of collapsed alveoli, ultimately improving tissue oxygenation.The use of HFNC in acute hypoxemic respiratory failure, post-extubation period, pre-intubation period, respiratory infection, and obstructive airway disease has been extensively studied, but there are very few studies regarding its use in cardiogenic pulmonary edema. This review provides the current understanding of the physiological effect of HFNC and its application in acute cardiogenic pulmonary edema (ACPE). We conducted a literature search on PubMed using appropriate terms and reviewed relevant articles published within the last 10 years. We found that initial therapy with HFNC in ACPE patients can improve oxygenation and respiratory rate. HFNC can potentially be an alternative to non-invasive positive-pressure ventilation in terms of initial oxygen therapy in patients with ACPE. There is a need for larger prospective studies to evaluate and develop guidelines to consider the use of HFNC in patients with ACPE. We also highlight the fact that if there is no improvement in arterial blood gas parameters after HFNC therapy, initiation of invasive ventilation should not be delayed.

Mas receptor activation attenuates allergic airway inflammation via inhibiting JNK/CCL2-induced macrophage recruitment

BackgroundDefective absorption of acute allergic airway inflammation is involved in the initiation and development of chronic asthma. After allergen exposure, there is a rapid recruitment of macrophages around the airways, which promote acute inflammatory responses. The Ang-(1−7)/Mas receptor axis reportedly plays protective roles in various tissue inflammation and remodeling processes in vivo. However, the exact role of Mas receptor and their underlying mechanisms during the pathology of acute allergic airway inflammation remains unclear. ObjectiveWe investigated the role of Mas receptor in acute allergic asthma and explored its underlying mechanisms in vitro, aiming to find critical molecules and signal pathways. MethodsMas receptor expression was assessed in ovalbumin (OVA)-induced acute asthmatic murine model. Then we estimated the anti-inflammatory role of Mas receptor in vivo and explored expressions of several known inflammatory cytokines as well as phosphorylation levels of MAPK pathways. Mas receptor functions and underlying mechanisms were studied further in the human bronchial epithelial cell line (16HBE). ResultsMas receptor expression decreased in acute allergic airway inflammation. Multiplex immunofluorescence co-localized Mas receptor and EpCAM, indicated that Mas receptor may function in the bronchial epithelium. Activating Mas receptor through AVE0991 significantly alleviated macrophage infiltration in airway inflammation, accompanied with down-regulation of CCL2 and phosphorylation levels of MAPK pathways. Further studies in 16HBE showed that AVE0991 pre-treatment inhibited LPS-induced or anisomycin-induced CCL2 increase and THP-1 macrophages migration via JNK pathways. ConclusionOur findings suggested that Mas receptor activation significantly attenuated CCL2 dependent macrophage recruitments in acute allergic airway inflammation through JNK pathways, which indicated that Mas receptor, CCL2 and phospho-JNK could be potential targets against allergic airway inflammation.

TRP channels in airway sensory nerves

Transient Receptor Potential (TRP) channels expressed in specific subsets of airway sensory nerves function as transducers and integrators of a diverse range of sensory inputs including chemical, mechanical and thermal signals. These TRP sensors can detect inhaled irritants as well as endogenously released chemical substances. They play an important role in generating the afferent activity carried by these sensory nerves and regulating the centrally mediated pulmonary defense reflexes. Increasing evidence reported in recent investigations has revealed important involvements of several TRP channels (TRPA1, TRPV1, TRPV4 and TRPM8) in the manifestation of various symptoms and pathogenesis of certain acute and chronic airway diseases. This mini-review focuses primarily on these recent findings of the responses of these TRP sensors to the biological stresses emerging under the pathophysiological conditions of the lung and airways.

Laryngopyocele: 10 Years’ Experience in a Tertiary Institution, South-South, Nigeria

Laryngopyocele is an infected laryngocele: Rarer than laryngocele. An estimated 8% of laryngoceles get infected and become laryngopyocele with features of acute airway obstruction and sepsis with resultant fatality. Laryngocele is more common in Caucasian males population after the 5th decades of life. Mostly acquired though could be congenital. Most are unilateral with no predominance for the left or the right. Recently, laryngocele is categorized into internal or mixed (combined). Laryngopyocele accounted for 0.15% of 1376 ENT surgical procedures done in our operative theatre in a period of 10 years. Both were males in their 3rd decade. The first case reported with clinical features of upper airway obstruction from left laryngopyocele. Plain radiographs and computed scan of the neck revealed features of right laryngocele with contralateral left laryngopyocele. The second patient had recurrent right laryngopyocele. Twice general practitioners previously operated upon him before presenting in our facility. The two cases were successfully managed through external approach under general anesthesia with a small size endotracheal intubation. The mean follow-up period was 4 years without recurrence. There is dearth of literature on this subject in our environment; therefore, this article is an addition to literature.

Endoscopic Lung Volume Reduction with Autologous Blood: What is the Evidence?

Biological lung volume reduction (BioLVR) is a novel and low-cost endobronchial treatment method aimed at reducing the volume of the target lung lobe using biological agents, including fibrin-based hydrogel, fibrinogen, and autologous blood (AB) with thrombin. BioLVR induces local inflammation, resulting in acute airway obstruction, resorption atelectasis, fibrosis, and finally tissue remodeling by contraction of the target lobe and reduction in the lung volume, similar to the application of hot water vapor and foam. In addition, patients with severe impairment in lung function and quality of life may refuses to undergo surgery, resulting in limited treatment options. In such complex clinical scenarios, BioLVR with AB appears to be a good therapeutic option. These treatment modalities resulted in favorable outcomes in patients with heterogeneous and bullous emphysema, pulmonary lymphangioleiomyomatosis, and giant bullous lesions. AB applications result in functional improvement, improvement in the quality of life, decrease in dyspnea scores, and reduction in the size of bullae. Based on the available evidence, application of AB for lung volume reduction is minimally invasive and well tolerated by patients. There was no incidence of pneumothorax or mortality. This review aimed to investigate the benefits, complications, and future perspectives of AB application as BioLVR in the treatment of hyperinflated lung diseases.

Microvasculature in murine tracheal allografts after combined therapy with clopidogrel and everolimus.

Survival after lung transplantation is mainly limited by the development of chronic lung allograft dysfunction. Previous studies have suggested T-cell mediated proliferation and microvascular changes in experimental small airways models as potential therapeutic targets. The aim of this study was to assess microvascular changes in murine orthotopic tracheal allografts after treatment with everolimus alone or in combination with clopidogrel. C57Bl/6 (H-2b) donor tracheas were orthotopically transplanted into CBA (H-2k) recipients. Mice received daily injections of everolimus (0.05 mg/kg) alone or combined with clopidogrel (1 mg/kg). Twenty-eight days after transplantation, ratio of the thickness of tracheal epithelium and lamina propria was measured as an indicator for chronic rejection. Additionally, graft oxygenation and graft perfusion were detected on postoperative days 4, 10 and 28. Quantitative reverse transcription polymerase chain reaction analysis was used for gene expression analysis. While syngeneic grafts showed a stable tissue pO2 and undisturbed microvascular perfusion, rejecting allografts had a drastic decline in both parameters as well as a flattened epithelium and an increased thickness of the lamina propria. Treatment with everolimus reduced allogeneic fibroproliferation, but had no protective effects on the microvasculature; polymerase chain reaction analysis indicated hypoxic stress and inflammation. Combining everolimus with clopidogrel improved microvascular integrity in the tracheal grafts, but had no synergistic effect in preventing obliterative bronchiolitis development. These data demonstrate that the ability of everolimus to reduce the development of post-transplant obliterative bronchiolitis is not caused by microvascular protection and has no synergistic effects with clopidogrel in acute airway rejection.

Airway exposure to perfluorooctanoate exacerbates airway hyperresponsiveness and downregulates glucocorticoid receptor expression in asthmatic mice.

BackgroundMultiple environmental risk factors play a vital role in the pathogenesis of asthma, which contribute to the phenotypic expression of asthma. Perfluorooctanoate (PFOA) is the most common and abundant perfluorocarbon (PFC) in humans, and it has been detected in water and the atmosphere worldwide. Glucocorticoid receptor (GR) is considered to exert a protective effect on asthma and is associated with the sensitivity to glucocorticoids. Dermal or oral exposure to PFOA has been shown to contribute various effects on airway inflammation in individuals with ovalbumin (OVA)-induced asthma. Notably, airway exposure has a critical contribution to the pathogenesis of asthma. However, the effect of airway exposure to PFOA on airway hyperresponsiveness (AHR) in patients with asthma is not currently understood.MethodsBALB/c mice were administered OVA to induce asthma. PFOA was then administered intratracheally to OVA-induced mice for seven days. Then we assessed the effect of airway exposure to PFOA on AHR and the regulation of the GR expression in asthmatic mice.ResultsThe results showed aggravated AHR and T helper type 2 (Th2) airway inflammation in asthmatic mice. Furthermore, these mice show a substantial decrease in the expression of the GR mRNA and protein.ConclusionsThese data strongly suggest that acute airway exposure to PFOA leads to Th2-related AHR and decreases GR expression, which may increase the difficulty in the treatment of asthma.

A novel system that continuously visualizes and analyzes respiratory sounds to promptly evaluate upper airway abnormalities: a pilot study

Although respiratory sounds are useful indicators for evaluating abnormalities of the upper airway and lungs, the accuracy of their evaluation may be limited. The continuous evaluation and visualization of respiratory sounds has so far been impossible. To resolve these problems, we developed a novel continuous visualization system for assessing respiratory sounds. Our novel system was used to evaluate respiratory abnormalities in two patients. The results were not known until later. The first patient was a 23-year-old man with chronic granulomatous disease and persistent anorexia. During his hospital stay, he exhibited a consciousness disorder, bradypnea, and hypercapnia requiring tracheal intubation. After the administration of muscle relaxant, he suddenly developed acute airway stenosis. Because we could not intubate and ventilate, we performed cricothyroidotomy. Subsequent review of our novel system revealed mild stridor before the onset of acute airway stenosis, which had not been recognized clinically. The second patient was a 74-year-old woman who had been intubated several days earlier for tracheal burn injury, and was extubated after alleviation of her laryngeal edema. After extubation, she gradually developed inspiratory stridor. We re-intubated her after diagnosing post-extubation laryngeal edema. Subsequent review of our novel system revealed serially increased stridor after the extubation, at an earlier time than was recognized by healthcare providers. This unique continuous monitoring and visualization system for respiratory sounds could be an objective tool for improving patient safety regarding airway complications.

Risk factors for unplanned reintubation caused by acute airway compromise after general anesthesia: a case-control study

BackgroundThis study aimed to identify the risk factors and evaluate the prognosis of unplanned reintubation caused by acute airway compromise (AAC) after general anesthesia.MethodsThis case-control study included surgical patients who underwent unplanned reintubation in the operating room and postanesthesia care unit after general anesthesia between January 1, 2014, and December 31, 2018. Cases due to AAC were matched 1:4 with randomly selected controls.ResultsA total of 123,068 patients were included, and reintubation due to AAC was performed in 36 patients (approximate incidence 0.03%). Univariable analysis revealed that male sex, age > 65, ASA physical status 3, sepsis, heart disease history, cerebral infarction history, Cormack Lehane grade, surgery type, fresh frozen plasma infusion, increased intubation duration, white blood cell count, and creatinine clearance rate were related to AAC-caused unplanned reintubation. Multivariable analysis revealed that age > 65 (OR = 7.50, 95% CI 2.47–22.81, P < 0.001), ASA physical status 3 (OR = 6.51, 95% CI 1.18–35.92, P = 0.032), head-neck surgery (OR = 4.94, 95% CI 1.33–18.36, P = 0.017) or thoracic surgery (OR = 12.56, 95% CI 2.93–53.90, P < 0.001) and a high fluid load (OR = 3.04, 95% CI 1.16–7.99, P = 0.024) were associated with AAC-caused unplanned reintubation. AAC-caused unplanned reintubation patients had longer postoperative hospital (OR = 5.26, 95% CI 1.57–8.95, P < 0.001) and intensive care unit days (OR = 3.94, 95% CI 1.69–6.18, P < 0.001).ConclusionsAge > 65, ASA physical status 3, head-neck or thoracic surgery and high fluid load were found to be associated with AAC-caused unplanned reintubation.