Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review

Respiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipient

understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia

SummaryInflammation is a double-edged sword in the outcome of pneumonia. On the one hand, an effective and timely inflammatory response is required to eliminate the invading respiratory pathogen. On the other, a toxic and prolonged inflammatory response may result in lung injury and poor outcomes, even in those receiving advanced medical care. This review focuses on recent understanding of the dynamics of the cytokine response, neutrophil activity, and responsiveness to cytokines and neutrophil lifespan as major elements of lung inflammation resulting in favorable or poor outcomes in lung infection primarily due to pneumococcus and influenza virus. Although some progress has been made in our understanding of the molecular mechanisms of the pneumonia inflammation axis composed of cytokines modulating neutrophil activation and neutrophil apoptosis, important questions remain to be answered. The degree of neutrophil activation, generation of reactive oxygen species, and the release of granule antimicrobial peptides play a key role in microbial pathogen clearance; however, prolonged neutrophil activation may contribute to lung injury and poor outcomes in pneumonia. Molecular markers of the mechanisms regulating neutrophil survival and apoptosis may help in the identification of novel therapeutic targets to modulate inflammation by inducing timely neutrophil apoptosis. A major task is to identify the mechanisms of dysregulation in inflammation leading to toxic responses, thereby targeting a biomarker and enabling timely therapies to modulate inflammation

Quality of Life and Lung Function in Survivors of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome

Abstract Editor's Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Survivors of acute respiratory distress syndrome (ARDS) have long-term impairment of pulmonary function and health-related quality of life, but little is known of outcomes of ARDS survivors treated with extracorporeal membrane oxygenation. The aim of this study was to compare long-term outcomes of ARDS patients treated with or without extracorporeal membrane oxygenation. Methods A prospective, observational study of adults with ARDS (January 2013 to December 2015) was conducted at a single center. One year after discharge, survivors underwent pulmonary function tests, computed tomography of the chest, and health-related quality-of-life questionnaires. Results Eighty-four patients (34 extracorporeal membrane oxygenation, 50 non–extracorporeal membrane oxygenation) were studied; both groups had similar characteristics at baseline, but comorbidity was more common in non–extracorporeal membrane oxygenation (23 of 50 vs. 4 of 34, 46% vs. 12%, P < 0.001), and severity of hypoxemia was greater in extracorporeal membrane oxygenation (median Pao2/Fio2 72 [interquartile range, 50 to 103] vs. 114 [87 to 133] mm Hg, P < 0.001) and respiratory compliance worse. At 1 yr, survival was similar (22/33 vs. 28/47, 66% vs. 59%; P = 0.52), and pulmonary function and computed tomography were almost normal in both groups. Non–extracorporeal membrane oxygenation patients had lower health-related quality-of-life scores and higher rates of posttraumatic stress disorder. Conclusions Despite more severe respiratory failure at admission, 1-yr survival of extracorporeal membrane oxygenation patients was not different from that of non–extracorporeal membrane oxygenation patients; each group had almost full recovery of lung function, but non–extracorporeal membrane oxygenation patients had greater impairment of health-related quality of life

Extracorporeal photopheresis as induction therapy in lung transplantation for cystic fibrosis: a pilot randomized trial

IntroductionExtracorporeal photopheresis (ECP) is a viable treatment that slows the progression of chronic lung allograft dysfunction. Despite its immunoregulatory potential, data on extracorporeal photopheresis as an induction therapy remain rather limited.MethodsWe conducted a pilot randomized controlled study on ECP as induction therapy in cystic fibrosis patients undergoing primary lung transplantation. Primary endpoints included safety, assessed based on the incidence of adverse events, treatment-related toxicity, and procedure-related complication rates; and feasibility, evaluated through the completion rate of scheduled ECP sessions, patient tolerability, and treatment discontinuation rates. Secondary endpoint consisted of an exploratory assessment of efficacy, using a composite measure that included three key components: freedom from biopsy-proven acute rejection within the first 12 months, absence of chronic lung allograft dysfunction at 36 months, and optimal graft function, defined as a predicted forced expiratory volume in the first second ≥ 90% at 36 months. Finally, exploratory endpoints included cell phenotypic and functional analyses, secreted immune protein profiling, and gene expression analysis for mechanistic insights. Patients were randomly assigned to receive either standard immunosuppressive therapy alone or standard therapy plus six sessions of extracorporeal photopheresis, with a follow-up period of 36 months.ResultsAmong 36 cystic fibrosis patients who underwent lung transplantation between 2018 and 2021 and met the eligibility criteria, 21 were randomized (9 to the study group and 12 to the control group). No patients in the treatment group experienced adverse events. The enrollment rate was 61%, and the treatment discontinuation rate was 22%. The clinical composite endpoint was achieved by 28.6% of patients in the treatment group and 16.7% in the control group. Exploratory endpoint analyses revealed significant decreases in pro-inflammatory cytokines, degranulating CD8+ T lymphocytes, and NK cells in the treatment group. Moreover, significant increases in Treg lymphocytes, IL-10-producing NK cells, and anti-inflammatory cytokines appeared to be associated with improved pulmonary function in the treatment group.ConclusionsInduction therapy with extracorporeal photopheresis is safe and feasible in lung transplantation for cystic fibrosis. Some clinical benefits appear to persist for the first 36 months of follow-up. Interestingly, a correlation between immunological modulation induced by extracorporeal photopheresis and pulmonary function was observed.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT03500575?cond=NCT03500575&rank=1, identifier NCT03500575

Chronic lung allograft dysfunction after lung transplantation - prevention, diagnosis and treatment in 44 European centers

Background: There is limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe. Methods: A structured questionnaire was sent to 71 centers in 24 countries. Questions were related to contemporary clinical practices for work-up, monitoring and treatment of CLAD. Number of lung transplant (LTx) procedures, patients in follow-up were collected. Results: Forty-four centers (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles 4.4-15.7). Preferred initial work-up for probable CLAD consisted of chest CT (inspiratory 91%, expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%), and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%), and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (CMV 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%), and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases. Conclusion: Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression, and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation

Criteria for clinical stability in hospitalised patients with community-acquired pneumonia

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