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Extracellular matrix remodeling in children with airway foreign-body aspiration
Lan Fang Tang1, Li Zhong Du, Zhi Min Chen
1Department of Respiratory Medicine, Zhejiang University Children's Hospital, School of Medicine, Zhugan Xiang, Hangzhou, China.
Insights
Airway foreign-body aspiration (FBA) in children triggers extracellular matrix remodeling, indicated by increased matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Hydroxyproline (HYP) levels also rise with longer foreign-body retention, suggesting potential airway remodeling.
Area of Science:
- Pediatric Pulmonology
- Biochemistry
- Cell Biology
Background:
- Airway foreign-body aspiration (FBA) in children can lead to significant respiratory complications.
- Extracellular matrix (ECM) remodeling plays a crucial role in tissue repair and fibrosis, but its involvement in FBA is not fully understood.
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are key regulators of ECM turnover.
Purpose of the Study:
- To investigate extracellular matrix remodeling in pediatric patients with FBA.
- To assess the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hydroxyproline (HYP) in bronchoalveolar lavage fluid (BALF) of children with FBA.
- To correlate these markers with the duration of foreign-body retention.
Main Methods:
- A cohort of 46 children with FBA and 12 healthy controls were studied.
- Bronchoalveolar lavage fluid (BALF) was collected to measure cell counts, MMP-9, TIMP-1, and HYP levels.
- Patients were categorized into three subgroups based on foreign-body retention duration (<7 days, 7-30 days, >30 days).
Main Results:
- MMP-9 and TIMP-1 expression were significantly higher in FBA patients compared to controls and increased with longer FB retention duration.
- Hydroxyproline (HYP) levels were significantly elevated in patients with FB retention exceeding 7 days.
- Mast cells were exclusively found in the BALF of FBA patients, and their presence correlated positively with MMP-9 and TIMP-1 levels.
Conclusions:
- FBA in children is associated with ECM remodeling, evidenced by increased MMP-9, TIMP-1, and HYP.
- The duration of foreign-body retention is a critical factor influencing the extent of ECM remodeling.
- These findings suggest that FBA may contribute to airway remodeling through the generation of MMPs and TIMPs, beyond mechanical obstruction.
Abstract:
The purpose of this study was to observe extracellular matrix remodeling in children with airway foreign-body aspiration (FBA) by detecting the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hydroxyproline (HYP) in bronchoalveolar lavage fluid (BALF). Forty-six children with FBA and 12 control subjects from 2002-2003 were enrolled in this study. The former were divided into three subgroups according to duration of foreign-body (FB) retention (subgroup 1, <7 days; subgroup 2, 7-30 days; subgroup 3, >30 days). Cell count, and levels of MMP-9, TIMP-1, and HYP in BALF were measured. The total number of cells and differential counts detected in BALF did not differ significantly between patients and controls (P > 0.05), while mast cells were found only in the BALF of patients. The positive rates of MMP-9 in controls, subgroup 1, subgroup 2, and subgroup 3 were 33.3%, 62.5%, 80.0%, and 93.3%, respectively, with a significant difference (P = 0.006). The positive rate of TIMP-1 in controls and subgroups 1, 2, and 3 were 33.3%, 62.5%, 80.0%, and 93.3%, respectively, with a significant difference (P < 0.001) as well. HYP levels in subgroups 2 and 3 were significantly more increased than in subgroup 1 and controls (all P < 0.001). Levels of MMP-9, TIMP-1, and HYP in patients were positively correlated with duration of FB retention (all P < 0.05), and levels of MMP-9 and TIMP-1 were also positively correlated with percentage of mast cells in BALF (all P < 0.05). The differences in MMP-9 and TIMP-1 before and after FB removed were not significant (P > 0.05), while HYP levels decreased significantly after FB were removed (P = 0.001). Our findings support the hypothesis that FBA may contribute not only to mechanical airway obstruction, but also possibly to eventual airway remodeling by generation of MMPs and TIMPs.
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