Pathophysiological Concepts and Management of Pulmonary Manifestation of Pediatric Inflammatory Bowel Disease

Abstract

Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed a systematic Medline search between April 1976 and April 2022. Different pathophysiological concepts were identified, including the shared embryological origin, “miss-homing” of intestinal based neutrophils and T lymphocytes, inflammatory triggering via certain molecules (tripeptide proline-glycine-proline, interleukin 25), genetic factors and alterations in the microbiome. Most pediatric IBD patients with PM are asymptomatic, but can show alterations in pulmonary function tests and breathing tests. In children, the pulmonary parenchyma is more affected than the airways, leading histologically mainly to organizing pneumonia. Medication-associated lung injury has to be considered in pulmonary symptomatic pediatric IBD patients treated with certain agents (i.e., mesalamine, sulfasalazine or infliximab). Furthermore, the risk of pulmonary embolism is generally increased in pediatric IBD patients. The initial treatment of PM is based on corticosteroids, either inhaled for the larger airways or systemic for smaller airways and parenchymal disease. In summary, this review article summarizes the current knowledge about PM in pediatric IBD patients, focusing on pathophysiological and clinical aspects.

Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections

“…A defective intestinal barrier function due to chronic inflammation has been demonstrated to facilitate antigens to translocate through the intestinal epithelium [11][12][13]. Antigens passing through leaky intestinal epithelium activate both dendritic cells [14] and macrophages.…”

“…Another molecular alteration that may play a role in both IBD and pulmonary manifestations is the dysregulation of protease activity [10,11]. During intestinal inflammation, the expression of matrix metalloproteinase (MMP) is increased, leading to a neutrophilmediated intestinal collagen proteolysis and rise in neutrophilic inflammation [26].…”

“…During intestinal inflammation, the expression of matrix metalloproteinase (MMP) is increased, leading to a neutrophilmediated intestinal collagen proteolysis and rise in neutrophilic inflammation [26]. Increased levels of epithelial and leukocyte MMP have already been associated with the pathogenesis of some inflammatory diseases of the lung, such as chronic obstructive pulmonary disease, and might be one cause of pulmonary manifestations of IBD [11].…”

“…The pathogenesis of respiratory involvement in IBD patients remains partially understood. The common embryological origin of the respiratory and gastrointestinal systems and their shared components of the mucosal immune system may explain the pathogenesis [10,11].…”

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease

“…On the other hand, it is noteworthy that expression of some biomolecules on the surface of capillary endothelial cells raises in the inflamed colon. The overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-Selectin, and E-Selectin is among the most important pathophysiological changes on the surface of capillary endothelial cells in damaged regions of the colon ( Zhao et al, 2019 ; Bui et al, 2020 ; Schmid et al, 2022 ).…”