Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

Abstract

Intraluminal pulmonary vein stenosis is a disease with significant morbidity and mortality, though recent progress has been made using multimodal therapy with antiproliferative agents. The aim of this study was to evaluate the association between aspiration and poor treatment response in patients with intraluminal pulmonary vein stenosis. A retrospective, single-center cohort analysis was performed of patients treated with a combination of imatinib mesylate and multimodal anatomic relief between March 2009 and November 2019. Analysis focused on 2-ventricle patients due to small numbers and clinical heterogeneity of single ventricle patients. Among the 84 patients included, 15 had single ventricle physiology and 69 had 2-ventricle physiology. Among the 2-ventricle group, multivariable analysis revealed that patients with clinical aspiration had nearly five times higher odds of poor treatment response than patients without aspiration (OR 4.85, 95% CI [1.37, 17.2], p = 0.014). Furthermore, male patients had higher odds of poor treatment response than their female counterparts (OR 3.67, 95% CI [1.04, 12.9], p = 0.043). Aspiration is a novel, potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology.

Management of Pediatric Pulmonary Vein Stenosis

“…Patients who are at risk of a poor outcome include those with a younger age and/or lower weight at presentation, a higher number of affected veins, higher severity of disease in the affected veins, severe secondary PH, presence of RV dysfunction, and aspiration. 13,29,35,[43][44][45][46][47][48] Patients with single-ventricle physiology are particularly vulnerable. Patients who respond to therapy thrive, require fewer and less frequent interventions, have shorter hospital stays following reintervention, and have declining RV pressure.…”

“…Lung disease of any kind, including BPD, interstitial lung disease, malacia, apnea, chronic atelectasis, lower respiratory infections, and aspiration, are associated with PVS. [19][20][21]31,48 Patients with aspiration, in particular, are more likely to have a poor treatment response. 48 It is unclear whether it is the inflammatory process associated with these conditions that is the initial nidus in the lungs that ultimately drives the fibromyxoid proliferation in the veins.…”

“…[19][20][21]31,48 Patients with aspiration, in particular, are more likely to have a poor treatment response. 48 It is unclear whether it is the inflammatory process associated with these conditions that is the initial nidus in the lungs that ultimately drives the fibromyxoid proliferation in the veins. Alternatively, the lung issues may simply be stretching or distorting the pulmonary veins secondary to arterial/bronchial dilation, lung hyperinflation, atelectasis, and airspace disease, which stimulates neointimal hyperplasia.…”

“…Further, a feeding evaluation is performed at diagnosis and following surgical interventions with the goal of eliminating the risk of aspiration. 48 In severe PVS cases, hemoptysis can occur as a result of alveolar or capillary hemorrhage or airway collaterals from vein atresia and insufficient pulmonary venous egress. Treatment is largely supportive-including positive-pressure ventilation-but may result in the need for a pneumonectomy when vein patency cannot be achieved.…”

Lung and Pleural Findings of Children with Pulmonary Vein Stenosis with and without Aspiration: MDCT Evaluation

“…These studies found that poor outcomes from PVS in children are associated with bilateral pulmonary vein involvement, smaller size and younger age at diagnosis, and underlying concomitant lung disease [9][10][11][12][13][14][15][16]. Among the studies investigating risk factors for poor outcomes in children with PVS, the most recent study, which demonstrated an association between aspiration and poor outcome in pediatric PVS, is receiving special attention because aspiration is a potentially modifiable risk factor [17].…”