Dataset Information

Efficacy and safety of whole-lung lavage for pulmonary alveolar proteinosis: a protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Pulmonary alveolar proteinosis (PAP) is an ultrarare disorder characterised by the accumulation of alveolar surfactant and the dysfunction of alveolar macrophages that results in hypoxemic respiratory failure. Whole-lung lavage (WLL) is currently the primary therapy for PAP. However, systematic evaluation of the clinical efficacy of WLL is lacking. We aim to perform a systematic review and meta-analysis of existing evidence to support WLL for the clinical treatment of PAP.

Methods and analysis

We will search the PubMed (MEDLINE), Cochrane Library, Embase, Web of Science and Google Scholar databases from inception to December 2021 for observational studies using WLL for the treatment of PAP. Two authors will independently screen the eligible studies, assess the quality of the included papers and extract the required information. Review Manager V.5.4 will be used to perform the meta-analysis. We will evaluate the overall quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. All steps of this protocol will be performed using the Cochrane Handbook for Preferred Reporting Items for Systematic Review and Meta-analysis statement.

Ethics and dissemination

This systematic review and meta-analysis will be based on published data. Therefore, ethical approval is not required. We will publish our results in a peer-reviewed journal.

Prospero registration number

CRD42022306221 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306221).

SUBMITTER: Liu S

PROVIDER: S-EPMC9021772 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of whole-lung lavage for pulmonary alveolar proteinosis: a protocol for a systematic review and meta-analysis.

Liu Shixu S Cui Xiangning X Xia Kun K Duan Yuanyuan Y Xiong Mengran M Li Guangxi G

BMJ open 20220420 4

<h4>Introduction</h4>Pulmonary alveolar proteinosis (PAP) is an ultrarare disorder characterised by the accumulation of alveolar surfactant and the dysfunction of alveolar macrophages that results in hypoxemic respiratory failure. Whole-lung lavage (WLL) is currently the primary therapy for PAP. However, systematic evaluation of the clinical efficacy of WLL is lacking. We aim to perform a systematic review and meta-analysis of existing evidence to support WLL for the clinical treatment of PAP.<h ...[more]

PMID: 35443958

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Project description:RationaleWhole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP.Methods18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled "rescue" WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group.ResultsThe primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30 versus 18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar-arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported.ConclusionsThis long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.

Project description:BackgroundThe incidence of silicosis has increased due to occupational silica exposure from artificial stone, with no treatments proven to halt or reverse the disease. Whole lung lavage (WLL) involves the instillation of fluid into the lungs to wash out silica particles and disease-causing inflammatory cells. This study aimed to determine the feasibility, safety, and possible benefit of WLL in patients with artificial stone silicosis.MethodsIn this prospective observational study, people with progressive silicosis with ground glass predominant radiological changes underwent WLL. High resolution computed tomography (HRCT) chest, X-ray velocimetry (XV), lung function tests, forced oscillation technique (FOT), and cardiopulmonary exercise tests (CPET) were performed before and six months after the procedure.ResultsEight patients underwent WLL between June 2021 and November 2022. Five participants had an improvement in the International Classification of High Resolution Computed Tomography for Occupational and Environmental Respiratory Diseases (ICOERD) CT scores and reduction in XV regional ventilation distribution pre- and six months post-WLL. There was no difference in lung function [annualized rate of change in forced vital capacity (FVC) % predicted mean difference (MD) 1.81; 95% CI: -1.53 to 5.15, P=0.27; forced expiratory volume in 1 second (FEV1) % predicted MD -1.13, 95% CI: -5.08 to 2.83, P=0.55; diffusing capacity for carbon monoxide (DLCO) % predicted MD -2.62, 95% CI: -10.04 to 4.80, P=0.46]. There was no significant difference in CPET or FOT measurements. Following WLL, all patients experienced transient throat discomfort, one had fever and two required oral antibiotics. There were no serious adverse events.ConclusionsWLL for artificial stone silicosis is safe in an expert centre who has experience in performing WLL in this population, and there may be limited benefit in selected patients. Further research is required to select those who will derive the most benefit.

Project description:Pulmonary alveolar proteinosis (PAP) is an umbrella term used to refer to a pulmonary syndrome which is characterized by excessive accumulation of surfactant in the lungs of affected individuals. In general, PAP is a rare lung disease affecting children and adults, although its prevalence and incidence is variable among different countries. Even though PAP is a rare disease, it is a prime example on how modern medicine can lead to new therapeutic concepts, changing ways and techniques of (genetic) diagnosis which ultimately led into personalized treatments, all dedicated to improve the function of the impaired lung and thus life expectancy and quality of life in PAP patients. In fact, new technologies, such as new sequencing technologies, gene therapy approaches, new kind and sources of stem cells and completely new insights into the ontogeny of immune cells such as macrophages have increased our understanding in the onset and progression of PAP, which have paved the way for novel therapeutic concepts for PAP and beyond. As of today, classical monocyte-derived macrophages are known as important immune mediator and immune sentinels within the innate immunity. Furthermore, macrophages (known as tissue resident macrophages (TRMs)) can also be found in various tissues, introducing e. g. alveolar macrophages in the broncho-alveolar space as crucial cellular determinants in the onset of PAP and other lung disorders. Given recent insights into the onset of alveolar macrophages and knowledge about factors which impede their function, has led to the development of new therapies, which are applied in the context of PAP, with promising implications also for other diseases in which macrophages play an important role. Thus, we here summarize the latest insights into the various forms of PAP and introduce new pre-clinical work which is currently conducted in the framework of PAP, introducing new therapies for children and adults who still suffer from this severe, potentially life-threatening disease.

Dataset Information

Efficacy and safety of whole-lung lavage for pulmonary alveolar proteinosis: a protocol for a systematic review and meta-analysis.

Introduction

Methods and analysis

Ethics and dissemination

Prospero registration number

Publications

Efficacy and safety of whole-lung lavage for pulmonary alveolar proteinosis: a protocol for a systematic review and meta-analysis.

Similar Datasets

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