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.
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.
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.
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.
Limited data are currently available regarding the course of COVID‐19 in lung and solid organ transplant recipients. We hereby present four cases of SARS‐CoV‐2 pneumonia in lung transplant recipients ...from our center, set in Milan, Italy. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; everybody received hydroxychloroquine, initial empiric antibiotic treatment with piperacillin/tazobactam, and high‐dose low molecular weight heparin. Clinical course seemed favorable in three of our patients, but one of them deteriorated after 10 days of hospitalization, probably due to an acute form of graft dysfunction triggered both by COVID‐19 and a nosocomial bacterial infection, and eventually died. Although short‐term prognosis could be considered benign in the majority of our patients, we should carefully monitor these individuals in order to detect early sign of clinical deterioration and graft dysfunction in the next few months.
Summary Inflammation 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.
To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF).
We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 ...patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls).
Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae.
The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.
Telemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of ...acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed.
Patients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre.
Sixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction.
The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.
Summary
Outcomes after transplantation of lungs (LuTX) treated with ex‐vivo lung perfusion (EVLP) are debated. In a single‐center 8 years of retrospective analysis, we compared: donors’ and ...recipients’ characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients’ survival of LuTX from standard donors compared with EVLP‐treated grafts. A total of 193 LuTX were performed. Thirty‐one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain‐dead donors. Recipients’ characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2/FiO2 276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05, more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration 28 days of ventilator‐free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05. ICU length of stay 4 (2; 9) vs. 6 (3; 12) days, P = 0.208, 28‐day survival (99% vs. 97%, P = 0.735), and 1‐year respiratory function were similar between groups. Log‐rank analysis (median follow‐up 2.5 years) demonstrated similar patients’ survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid‐term outcomes.
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 recipients.
Background: Immunodeficiencies (IDs) are conditions caused by immune system dysfunctions which predispose to chronic infections. Cystic fibrosis (CF) patients are characterized by the presence of ...bronchiectasis filled with hyper-viscous secretions that constitute the ideal environment for infections. Although CF and IDs might share similarities in the pathophysiological mechanism of bronchiectasis development, they each offer different treatment options. We hypothesize that the introduction of a bundle of tests would increase the number of ID diagnoses among adults with Cystic Fibrosis Transmembrane conductance Regulator (CFTR) dysfunction. Objectives: The primary objectives of this study were (1) assessing the prevalence of IDs in CF and (2) defining clinical characteristics of adults with both CF and IDs. The secondary objectives were: (1) assessing the prevalence of IDs in CFTR-Related Disorder (CFTR-RD) patients; (2) comparing the prevalence of IDs in CF and CFTR-RD; (3) comparing the prevalence of treatable IDs in CF and CFTR-RD. Design: We conducted an observational, prospective, consecutive study on a cohort of 190 adult patients affected by CF or CFTR-RD. Methods: Blood samples underwent a standardized immunological screening, including complete white blood count, IgG, IgA, IgM, IgG subclasses, total IgE, lymphocyte subsets, and HIV test. Comprehensive clinical history was assessed to identify risk factors for secondary IDs. Results: We identify a high prevalence of immunodeficiencies among the entire cohort: 34 (20.1%) CF patients and 10 (47.6%) CFTR-RD patients are diagnosed with IDs via a blood screening. No statistically significant difference in terms of clinical characteristics was found between immunocompromised and immunocompetent CF patients. Conclusion: We identify a high prevalence of immunodeficiencies in both CF and CFTR-RD.
Introduction
Sinus disease (SD) in cystic fibrosis (CF) is a known risk factor for disease progression, the upper airways (UAW) being a site of primary colonization with Pseudomonas aeruginosa. UAW ...may function as reservoir for graft colonization after lung transplantation (LuTx), increasing risk of rejection. Aims of this study were to assess the burden of sinus disease in CF LuTx recipients, considering patient‐reported symptoms, endoscopically documented signs and microbiological isolates, comparing colonization between upper and lower airways.
Methods
A prospective, observational study was performed on consecutive CF LuTx recipients, recording history, symptoms, and management of SD. Nasal lavage (NL) was evaluated for UAW colonization, with nasal inspection during bronchoscopy and bronchoalveolar lavage (BAL) used to assess lower airways if clinically indicated.
Results
Hundred and fifty‐four patients were included. Symptoms of SD were reported in 96 (62%) individuals; 87 (56%) had prior sinus surgery. Only 8 (13%) of 60 individuals undergoing bronchoscopy presented completely normal findings of the nasal cavity. Thirty‐six (60%) patients presented the same isolates on both NL and BAL. Polyps and mucosal alterations were significantly less frequently seen endoscopically in patients with normal flora in NL microbiology (respectively, 26% vs 70%, P = .003, and 35% vs 68%, P = .013).
Conclusions
Symptoms of SD affected more than 60% of CF LuTx recipients. Nasal endoscopic inspection identified alterations in 55%. The majority of patients presented the same isolates both on NL and BAL performed on the same visit. These results strongly support a role of paranasal sinuses as “reservoir” for descending re‐colonization of the lung graft.
Chronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has ...been scarcely investigated in the setting of lung transplantation.
We conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules.
Results showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome.
Results of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.
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