Methods: This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018. Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD (SGRQ-c).
Results: Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS). The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001). Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001). Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001). However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187). There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.
Conclusion: Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components. Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components.
METHODS: Pre-differentiation of eGFP-expressing AFMSCs to lung epithelial progenitor-like cells (LEPLCs) was established under a modified small airway growth media (mSAGM) for 7-day induction. Pre-differentiated AFMSCs were intratracheally injected into porcine pancreatic elastase (PPE)-induced emphysema mice at day 14, and then inflammatory-, fibrotic-, and emphysema-related indices and pathological changes were assessed at 6 weeks after PPE administration.
RESULTS: An optimal LEPLCs pre-differentiation condition has been achieved, which resulted in a yield of approximately 20% lung epithelial progenitors-like cells from AFMSCs in a 7-day period. In PPE-induced emphysema mice, transplantation of LEPLCs significantly improved regeneration of lung tissues through integrating into the lung alveolar structure, relieved airway inflammation, increased expression of growth factors such as vascular endothelial growth factor (VEGF), and reduced matrix metalloproteinases and lung remodeling factors when compared with mice injected with AFMSCs. Histopathologic examination observed a significant amelioration in DNA damage in alveolar cells, detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), the mean linear intercept, and the collagen deposition in the LEPLC-transplanted groups.
CONCLUSION: Transplantation of predifferentiated AFMSCs through intratracheal injection showed better alveolar regeneration and reverse elastase-induced pulmonary emphysema in PPE-induced pulmonary emphysema mice.