246 - Tracheal Aspirate-Based Study on the Pathophysiology of BPD with Bubbly/Cystic Findings on Chest X-rays.

Publication Number: 246.6563

Hirokazu Arai, Akita Red Cross Hospital, Akita, Akita, Japan; Masato Ito, Akita Redcross hospital, Akita shi, Akita, Japan; Kiichi Takahashi, Japanese Red Cross Akita Hospital., Akita, Akita, Japan; Shozo Ota, 秋田赤十字病院　新生児科, Akita, Akita, Japan; Tomoo Ito, Akita redcross hospital, Akita, Akita, Japan; Tsutomu Takahashi, 秋田大学医学部小児科, Akita, Akita, Japan

Background: Preterm infants with bubbly/cystic lung patterns on chest X-rays (CXR) within the first month indicate the parenchymal phenotype of bronchopulmonary dysplasia (BPD). Early identification allows timely intervention in severe BPD. Tracheal aspirates (TA) are crucial for evaluating lung pathophysiology.

Objective: To investigate the pathophysiology of bubbly/cystic lungs by analyzing TA from lungs with diffuse bubbly/cystic patterns on CXR.

Design/Methods: TA were collected once during clinically indicated tracheal washes in 30 preterm infants born at < 28 weeks’ gestation at 3–4 weeks of life. Aspirates were centrifuged to separate supernatants and cellular components. Supernatants were analyzed for cytokines (IL-1β, IL-6, IL-10), MMP-9, and desmosine via ELISA. Cells were immunostained with CD68 antibodies (monocyte/macrophage marker), and large CD68-positive cells were qualitatively evaluated. Infants were grouped by CXR findings one-week post-aspirate: bubbly/cystic (group B) or non-bubbly/cystic (non-B). Bubbly/cystic lungs were defined by diffuse small bubbly/cystic areas and linear shadows in at least three of four lung regions. CXR readings were blinded and assessed by two neonatologists. Clinical short-term outcomes were retrospectively examined.

Results: No significant differences were observed in gestational age, birth weight, or each humoral factors between group B (n=11) and non-B (n=19) (Table 1, 2). MMP-9/IL-6 (p < 0.01) and Desmosine/IL-6 (p < 0.001) ratios were significantly higher in group B. Large CD68-positive cells, which often had a granular appearance, were more prevalent in non-B (p < 0.01). Using the NIH 2018 BPD severity classification, severe cases (grade≧2) were more frequent in group B, and discharge with home oxygen therapy was significantly higher in group B.

Conclusion(s): Chronic intrauterine infections have been reported to alter fetal immune responses and downregulate inflammatory cytokine responses. To distinguish whether the increases in protease and desmosine were due to acute or chronic inflammation, we calculated MMP-9/IL-6 and desmosine/IL-6 ratios. Increases in these ratios suggest that the bubbly/cystic lung changes are associated with protease activity and elastin degradation and that these dynamics may be persistent changes by chronic intrauterine infection. The lack of large CD68-positive cells, indicative of mature macrophages, in group B suggests that the resolution of inflammation may be delayed compared to non-B. These markers may help identify infants at risk for sever BPD and can compensate for the disadvantage of variability of volume in TA fluid collection.

Table1. Patient characteristics with or without bubbly/cystic lungs.
PAS2025 table1.pdfMAP, mean airway pressure. Data are expressed as median (range) or number (%).

Table2. Tracheal aspirate analysis with or without bubbly/cystic lungs.
PAS2025 table2.pdfData are expressed as median (range) or number (%).

Table1. Patient characteristics with or without bubbly/cystic lungs.
PAS2025 table1.pdfMAP, mean airway pressure. Data are expressed as median (range) or number (%).

Table2. Tracheal aspirate analysis with or without bubbly/cystic lungs.
PAS2025 table2.pdfData are expressed as median (range) or number (%).