Novel approaches to the prediction and diagnosis of pulmonary complications in the paediatric haematopoietic stem cell transplant patient

Abstract

Purpose of reviewHaematopoietic stem cell transplant (HSCT) remains the only curative treatment option for many children with relapsed leukaemia, primary immunodeficiencies and haemoglobinopathies. Unfortunately, infectious and noninfectious pulmonary complications following HSCT continue to cause significant morbidity and mortality. This review will focus on recent advances in the field that enhance clinically available diagnostic tools and the role of novel diagnostic techniques.Recent findingsResearch continues to highlight the role of standard diagnostic modalities, including imaging using computed topography chest and Fluorodeoxyglucose-positron emission tomography (FDG-PET) in the diagnosis of posttransplant pulmonary infections. Similarly, bronchoalveolar lavage using bronchoscopy to obtain samples for microbiological analysis remains an important tool in the clinical and diagnostic algorithm for these children. The application of more novel diagnostic techniques such as metagenomic next-generation sequencing and the use of specific biomarkers remain potential future tools in children in whom the aetiology of posttransplant lung disease is unknown. The impact of the pulmonary microbiome on infectious and noninfectious pulmonary disease post HSCT is a future research direction.SummaryPulmonary infectious complications post HSCT remain a devastating complication for children and their families. Despite improvements in standard and novel diagnostic modalities, the aetiology of pulmonary disease remains unknown for many patients. There is an urgent need for ongoing collaborative research to bridge this critical knowledge gap and lead to better patient outcomes.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation

“…HCT is often the only curative therapy for patients with malignancy, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. However, direct chemotherapy toxicity, opportunistic infection and alloreactive inflammation can cause pulmonary injury in up to 40% of patients [2][3][4] , with hospital mortality rates approaching 50% when mechanical ventilation is required 5,6 . setting, we applied metatranscriptomic sequencing to BAL from prospectively enrolled pediatric patients who have undergone HCT to characterize the pulmonary microbiome landscape, closely monitor occult infections and capture lung gene expression profiles.…”

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients

“…1 HCT is often the only curative therapy for patients with life-limiting diseases such as malignancy, bone marrow failure, and inborn errors of immunity, hemoglobin, and metabolism. However, direct chemotherapy toxicity, opportunistic infection, and/or alloreactive inflammation can lead pulmonary injury in up to 40% of patients, [2][3][4][5][6] which can lead to hospital mortality rates approaching 50% when mechanical ventilation is required. [7][8][9] Given the severity of lung disease in this population, a deeper understanding of the pulmonary microenvironment is needed to develop next-generation diagnostic tests and treatments that will improve survival rates.…”