Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-ß.

Purpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-ß regulation. Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-ß, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers. Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-ß was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-ß, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon. Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-ß. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.

Complex Evaluation of Surfactant Protein A and D as Biomarkers for the Severity of COPD.

Purpose: Pulmonary surfactant proteins A (SP-A) and D (SP-D) are lectins, involved in host defense and regulation of pulmonary inflammatory response. However, studies on the assessment of COPD progress are limited. Patients and Methods: Pulmonary surfactant proteins were obtained from the COPD mouse model induced by cigarette and lipopolysaccharide, and the specimens of peripheral blood and bronchoalveolar lavage (BALF) in COPD populations. H&E staining and RT-PCR were performed to demonstrate the successfully established of the mouse model. The expression of SP-A and SP-D in mice was detected by Western Blot and immunohistochemistry, while the proteins in human samples were measured by ELISA. Pulmonary function test, inflammatory factors (CRP, WBC, NLR, PCT, EOS, PLT), dyspnea index score (mMRC and CAT), length of hospital stay, incidence of complications and ventilator use were collected to assess airway remodeling and progression of COPD. Results: COPD model mice with emphysema and airway wall thickening were more prone to have decreased SP-A, SP-D and increased TNF-α, TGF-ß, and NF-kb in lung tissue. In humans, SP-A and SP-D decreased in BALF, but increased in serum. The serum SP-A and SP-D were negatively correlated with FVC, FEV1, FEV1/FVC, and positively correlated with CRP, WBC, NLR, mMRC and CAT scores (P < 0.05, respectively). The lower the SP-A and SP-D in BALF, the worse the lung function and the increased probability of complications and ventilator use. Moreover, the same trend emerged in COPD patients grouped according to GOLD severity grade (Gold 1-2 group vs Gold 3-4 group). The worse the patient's condition, the more pronounced the change. Conclusion: This study suggests that SP-A and SP-D may be related to the progression and prognostic evaluation of COPD in terms of airway remodeling, inflammatory response and clinical symptoms, and emphasizes the necessity of future studies of surfactant protein markers in COPD.

The lower the eosinophils, the stronger the inflammatory response? The relationship of different levels of eosinophils with the degree of inflammation in acute exacerbation chronic obstructive pulmonary disease (AECOPD).

BACKGROUND: Blood eosinophil levels are a known marker for the effects of therapy in patients with chronic obstructive pulmonary disease (COPD). This study aimed to clarify the cutoff values for blood eosinophils (EOS) to predict exacerbation risk and prognosis of acute exacerbation COPD (AECOPD) and investigate their correlation using inflammatory indicators and clinical characteristics. METHODS: In this observational study of 174 patients with AECOPD, we assessed the relationship between EOS and COPD. According to the percentage of blood EOS, patients were grouped into two groups (Group 1: EOS <2%, n=98; Group 2: EOS ≥2%, n=76), and Group 2 was further divided into Group A (2%≤ EOS <4%) and Group B (EOS ≥4%) based on a cutoff value of 4%. Patients received standardized treatment after collection of peripheral blood specimen. Associations of EOS with laboratory indicators before any treatment in hospital and with clinical data were compared. RESULTS: Patients in Group 1 showed significantly severe inflammation, worse pulmonary function, longer length of stay (LOS) (P<0.001), higher mMRC score (P<0.05), higher CAT score (P<0.05), higher rates of mortality (P<0.05), and greater noninvasive mechanical ventilation usage (P<0.05) compared with Group 2. Intriguingly, the CRP, total mMRC and CAT scores of patients in Group A were significantly lower than those in Group B (P<0.001; P<0.01; P<0.05, respectively). Pearson correlation analysis showed that a low percentage blood eosinophil level was negatively associated with higher WBC count (r=-0.155, P<0.05), NLR (r=-0.227, P<0.01) and CRP (r=-0.308, P<0.01). CONCLUSIONS: Different cutoff values for percentage blood EOS might be useful biomarkers for predicting the severity of exacerbation and prognosis of inpatients with AECOPD.