Single Lung Transplant Remains a Viable Option for Patients With Severe Secondary Pulmonary Hypertension.

BACKGROUND: Although double lung transplant is recommended in patients with severe secondary pulmonary hypertension (SPH), our institutional experiences suggest a role for single lung transplant in these patients. Here, we review our experience prioritizing single lung transplant in patients with SPH to minimize their surgical burden. METHODS: We conducted a retrospective review of our lung transplant database to identify patients with SPH who underwent single lung transplant. Patients were stratified as either mild SPH (mean pulmonary artery pressure 25-40 mm Hg) or severe SPH (mean pulmonary artery pressure >40 mm Hg). Singe lung recipients without PH transplanted over the same time were also examined. RESULTS: Between January 2017 and December 2019, 318 patients underwent single lung transplantation; 217 had mild SPH (68%), and 59 had severe SPH (18.5%). Forty-two patients without PH underwent single lung transplant. When the groups were compared, significantly higher pulmonary vascular resistance was noted in the severe SPH group, and obesity was noted in both the mild and severe SPH groups. Although the severe SPH group required more intraoperative cardiopulmonary support (37.3% versus 10.3% versus 4.7%, P < 0.05), there were no significant differences in most major postoperative parameters, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Survival 1 y posttransplant was not significantly different among the groups (93.2% versus 89.4% versus 92.9%, P = 0.58). CONCLUSIONS: Our experience supports the option of single lung transplantation with appropriate intraoperative mechanical circulatory support in patients with SPH. This strategy is worth pursuing, especially with ongoing donor lung shortages.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6-6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as "alarmins". Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

COVID-19 in lung transplant recipients.

Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.

Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA).

OBJECTIVE: In the SOLANA trial, we sought to physiologically characterize benralizumab's onset of effect and maintenance of that effect for patients with severe eosinophilic asthma. METHODS: SOLANA (NCT02869438) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, Phase IIIb study conducted at 49 centers in six countries (Chile, Germany, Hungary, the Philippines, South Korea, and the United States). Eligible patients with baseline blood eosinophil counts ≥300 cells/µL were randomized to subcutaneous benralizumab (30 mg) or placebo administered at Days 0, 28, and 56. The primary endpoint was the average change from baseline in prebronchodilator forced expiratory volume in 1 s (pre-BD FEV1) during the Day 28‒Day 84 period for benralizumab vs placebo. Secondary endpoints included patient-reported outcomes (PROs). A subset of patients participated in a whole-body plethysmography substudy. Safety was also assessed. RESULTS: In total, 233 patients were randomized to benralizumab (n=118) or placebo (n=115). Improvement from baseline in pre-BD FEV1 with benralizumab 30 mg was not statistically significant compared with placebo (least-squares mean change difference [95% confidence interval] 57 mL [-22 to 135]; p=0.16). Compared with placebo, benralizumab demonstrated early (Day 7) nonstatistically significant improvements in whole-body plethysmography assessments of hyperinflation and clinically meaningful improvements in PRO measures (Asthma Control Questionnaire 6 at Day 14 and St. George's Respiratory Questionnaire at Day 28), which were maintained over the treatment period. Benralizumab's safety profile was commensurate with previously reported studies. CONCLUSION: The observed early changes in lung volume despite relatively small improvements in airflow obstruction suggest that the anti-inflammatory effect of benralizumab may be manifested as deflation over time for patients with hyperinflation, who potentially have a greater degree of airway remodeling. This early effect could partially explain the rapid PRO improvements observed for certain patients.