Pulmonary Therapy最新文献

Introduction: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health.

Methods: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO₂).

Results: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO₂ compared to the P group.

Conclusions: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.

Adults with obesity may develop asthma that is ineffectively controlled by inhaled corticosteroids and long-acting beta-adrenoceptor agonists. Mechanistic and translational studies suggest that metabolic dysregulation that occurs with obesity, particularly hyperglycemia and insulin resistance, contributes to altered immune cell function and low-grade systemic inflammation. Importantly, in these cases, the same proinflammatory cytokines believed to contribute to insulin resistance may also be responsible for airway remodeling and hyperresponsiveness. In the past decade, new research has emerged assessing whether hypoglycemic therapies impact comorbid asthma as reflected by the incidence of asthma, asthma-related emergency department visits, asthma-related hospitalizations, and asthma-related exacerbations. The purpose of this review article is to discuss the mechanism of action, preclinical data, and existing clinical studies regarding the efficacy and safety of hypoglycemic therapies for adults with obesity and comorbid asthma.

Introduction: Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness.

Methods: This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV₁) after treatment versus at inclusion.

Results: In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters.

Conclusion: TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV₁.

Introduction: Treatment of prolonged air leak due to secondary spontaneous pneumothorax is challenging. Autologous blood patch pleurodesis (ABPP) is a treatment option. Previous evidence is reliant on single-centre series and underpowered trials and is mostly described in air leaks post cardiothoracic intervention. There are no United Kingdom (UK) wide data.

Methods: Members of the UK Pleural Society were surveyed for their practice and for patients who underwent blood patch. There were 16 respondents from 333 members. Twelve had performed the procedure, and six had kept records and could submit data. Basic demographics, intervention and clinical details of patients were then collected. The study was sponsored by the Audit Department of Northumbria Healthcare NHS Foundation Trust (reference 8124), and Caldicott Clearance for data sharing was provided by the Trust's Information Goverance Board (reference C4221). There was no requirement for informed consent.

Results: Data for 12 patients that received ABPP between 2014 and 2022 in six respiratory centres were assessed. The aetiology of the secondary pneumothoraces was mostly due to chronic obstructive pulmonary disease and end-stage interstitial lung disease. The patients had a median age of 75 years. The median air leak time before ABPP was 17 days. A total of 50-100 ml of blood was used for ABPP. Five patients had two attempts at ABPP. Air leak resolved in six patients (50%). Four patients had pleural apposition prior to ABPP. Four patients were diagnosed with hospital-acquired pneumonia following ABPP.

Conclusion: This is the only UK-wide retrospective case series of ABPP of 'medical' patients with secondary pneumothorax. There is widespread variation in care. No formal conclusions can be drawn, and much larger robust datasets are required. An application has been made to the European Respiratory Society to incorporate ABPP within the International Collaborative Effusion database.

Introduction: Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2-17 years.

Methods: Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight-age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods.

Results: Mean phenylephrine total exposure (AUC_∞) for children aged 2-5, 6-11, and 12-17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (C_max) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (T_max) ranged from 0.17 to 1.5 h, and elimination half-life (t_½,β) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,_scaled) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed.

Conclusion: A dosing schedule with additional weight-age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and C_max for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. TRIAL REGISTRATION: Clintrials.gov NCT00762567, registered 30 September 2008.

Pulmonary arterial hypertension (PAH) is a rare disease caused by high pressure in the blood vessels leading from the heart to the lung. PAH affects many parts of a patient's life, which means that patients should be managed by a clinical team of different specialists, including doctors, advance practice providers, nurses, social workers, and therapists. This article is co-authored by a patient living with PAH and an acute care nurse practitioner specializing in the management of patients with pulmonary hypertension. In the first section of this commentary, the patient describes her experience of living with PAH. The specialist nurse practitioner then discusses the management of PAH, to provide a clinician perspective in the context of the patient's experiences.

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation.

Introduction: There is lack of consensus on what constitutes best practice when assessing extubation readiness in children. This systematic review aims to synthesize data from existing literature on pre-extubation assessments and evaluate their diagnostic accuracies in predicting extubation failure (EF) in children.

Methods: A systematic search in PubMed, EMBASE, Web of Science, CINAHL, and Cochrane was performed from inception of each database to 15 July 2021. Randomized controlled trials or observational studies that studied the association between pre-extubation assessments and extubation outcome in the pediatric intensive care unit population were included. Meta-analysis was performed for studies that report diagnostic tests results of a combination of parameters.

Results: In total, 41 of 11,663 publications screened were included (total patients, n = 8111). Definition of EF across studies was heterogeneous. Fifty-five unique pre-extubation assessments were identified. Parameters most studied were: respiratory rate (RR) (13/41, n = 1945), partial pressure of arterial carbon dioxide (10/41, n = 1379), tidal volume (13/41, n = 1945), rapid shallow breathing index (RBSI) (9/41, n = 1400), and spontaneous breathing trials (SBT) (13/41, n = 5652). Meta-analysis shows that RSBI, compliance rate oxygenation pressure (CROP) index, and SBT had sensitivities ranging from 0.14 to 0.57. CROP index had the highest sensitivity [0.57, 95% confidence interval (CI) 0.4-0.73] and area under curve (AUC, 0.98). SBT had the highest specificity (0.93, 95% CI 0.92-0.94).

Conclusions: Pre-extubation assessments studied thus far remain poor predictors of EF. CROP index, having the highest AUC, should be further explored as a predictor of EF. Standardizing the EF definition will allow better comparison of pre-extubation assessments.

Despite the latest developments in therapeutic agents targeting airway endotypes, a significant proportion of patients with asthma and chronic obstructive pulmonary disease (COPD) remain symptomatic. Endoscopic therapies have a complementary role in the management of these airway diseases. The sustained efficacy of bronchial thermoplasty (BT) among patients with asthma over 10 years has been encouraging, as it has been shown to improve symptom control and reduce hospital admissions and exacerbations. Studies suggest that BT helps ameliorate airway inflammation and reduce airway smooth muscle thickness. While studies suggest that it is as effective as biologic agents, its role in the management of severe asthma has yet to be clearly defined and GINA 2022 still suggests limiting its use to patients with characteristics of the various populations studied. Conversely, bronchoscopic lung volume reduction has shown promise among patients with advanced COPD. Rigorous patient selection is important. Patients with minimal collateral ventilation (CV) and higher heterogeneity index have shown to benefit the most from endobronchial valve (EBV) therapy. For those with ongoing CV, endobronchial coils would be more appropriate. Both therapeutic modalities have demonstrated improved quality of life, effort tolerance, and lung function indices among appropriately selected patients. The emerging evidence suggests that endoscopic procedures among airway disease still have a substantial role to play despite the development of new therapeutic options.

Asthma is the most common chronic childhood condition and is a risk factor for severe respiratory viral infections. Thus, early during the coronavirus disease 2019 (COVID-19) pandemic there was concern that children with asthma would be at risk for severe COVID-19 illness and that asthma control could worsen as a result of the pandemic. This article seeks to summarize what was learned in the early stages of the pandemic about the impact of COVID-19 on children with asthma. We review evidence from several studies that demonstrated a significant decline in asthma morbidity in the first year of the pandemic. Additionally, we describe several potential mechanisms that may explain the reduced frequency in childhood asthma exacerbations as well as review lessons learned for future management of childhood asthma. While the COVID-19 pandemic initially brought uncertainty, it soon became clear that the pandemic had several positive effects for children with asthma. Now we can apply the lessons that were learned during the pandemic to re-examine asthma care practices as well as advocate for best approaches for asthma management.