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

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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P0569ACUTE KIDNEY INJURY AFTER LUNG TRANSPLANTATION: INCIDENCE, RISK FACTORS AND OUTCOMES IN A MONOCENTRIC RETROSPECTIVE COHORT STUDY

Abstract Background and Aims Acute kidney Injury (AKI) occurs in more than 50% of patients after lung transplantation (LTx). Our aim was to describe the incidence, risk factors and outcomes associated with AKI after LTx in a retrospective monocentric cohort study. Method We studied all recipients of LTx (&amp;gt; 16 years of age) occurring at Ospedale Maggiore Policlinico Milano between Jan 1st 2015 and Dec 31st 2017. AKI was defined according to KDIGO classification, eGFR was calculated according to CKD (Chronic Kidney Disease) Epidemiology Collaboration formula and CKD was defined by an eGFR&amp;lt; 60 ml/min per 1.73 m2. Chi square, Fisher exact test, t.-test and logistic regression were used to define risk factors for AKI in the early post-surgical period and for CKD at 1 and 2 years after LTx. AKI-related survival was estimated using Kaplan Meyer model. Results Of 78 LTx patients enrolled in our Center, 50% of patients was affected by cystic fibrosis. Median age at transplant was 43 years (27-55); median follow- up was 31 months (20-40). Survival rate was 80.77% at 1 year, 69.23% at 2 years and 66.67% on Dec 31st 2019 (last follow-up). AKI occurred in 42 (53.85%) patients within the first week after LTx, respectively grade I and II in 12 each (15.38%) and grade III in 18 (23.08%) patients. Pre-transplant low albumin levels and hypertension were independently associated with AKI at univariate and multivariate (p= 0.0018 and 0.0004 respectively) analysis. Pre-transplant low albumin levels, pre-transplant ECMO-use, hypertension, ECMO-use during transplant surgery were associated with severe AKI in univariate analysis but only pre-transplant hypertension and ECMO-use during transplant surgery were independently associated in the multivariate one (p=0.0266 and 0.0463 respectively). Survival was significantly reduced in patients affected by AKI (p=0.035); this observation became strongly significant when only mild and moderate (grade I and II) AKI was considered (p=0.0071). CKD was diagnosed in 38.09% of patients at 1 year and 35.18% at 2 years. While numerous risk factors were related to the occurrence of CKD at 1 and 2 years after LTx at univariate analysis, only grade III AKI remained independently associated with CKD at multivariate analysis (p= 0.0081 for 1 year-CKD, p=0.0154 for 2 year-CKD). Conclusions In our population, AKI after LTx occurred in about half of the patients and was predicted by history of hypertension, low albumin levels and hemodynamic instability during the surgery. Mild-moderate AKI, often clinically underestimated, was strongly associated with reduced survival. Severe forms of AKI were predictive of occurrence of CKD. </jats:sec