International Journal of COPD (Dec 2020)

Relationship Between Proteinase with a Disintegrin and a Metalloproteinase Domain-9 (ADAM9), Inflammation, Airway Remodeling, and Emphysema in COPD Patients

  • Cui L,
  • Li H,
  • Xie M,
  • Xu X,
  • Zhang YM,
  • Wang W,
  • Dou S,
  • Xiao W

Journal volume & issue
Vol. Volume 15
pp. 3335 – 3346

Abstract

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Liwei Cui,1 Haijun Li,2 Mengshuang Xie,1 Xia Xu,2 Yingmei Zhang,3 Wei Wang,1 Shuang Dou,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Cadre Health Care, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 3Department of Pulmonary Medicine, Linyi People’s Hospital, Linyi, People’s Republic of ChinaCorrespondence: Wei XiaoDepartment of Pulmonary Medicine, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, People’s Republic of ChinaEmail [email protected] and Objective: The link between ADAM9 and airway remodeling and emphysema severity in COPD patients has not been elucidated. Here, we investigated the relationship between ADAM9 levels in sputum and airway epithelium and the clinical characteristics of COPD patients.Methods: A sputum cohort and a lung tissue cohort were included in the study. Pulmonary function and computed tomography data were analyzed in COPD patients, non-COPD smokers, and non-smokers. Soluble ADAM9 and interleukin 8 (IL-8) levels in sputum supernatants as well as surface ADAM9 expression in airway epithelium were detected. Emphysema scores were calculated by the percentage of low attenuation area (%LAA-950), and airway remodeling was measured via airway thickening and loss of airway counts.Results: Both soluble ADAM9 levels in sputum and relative surface ADAM9 expression in airway epithelium were increased in COPD patients. Sputum ADAM9 levels were negatively correlated with forced expiratory volume in 1 s of predicted (FEV1% of predicted) and positively correlated with sputum IL-8 levels, but not with CT measured emphysema nor airway remodeling. The ADAM9 expression in airway epithelia was positively correlated with %LAA-950 and airway wall thickening parameters (wall area percentage, WA%; the square root of the wall area in a standard airway with a 10 mm internal perimeter, Pi-10), while negatively correlated with airway counts derived from the 4th to 9th bronchial generations.Conclusion: Airway ADAM9 levels in sputum and airway epithelium were both elevated in COPD patients compared to non-COPD controls. Sputum ADAM9 seemed to be associated with inflammatory responses in COPD, while epithelial ADAM9 was more correlated with emphysema and airway remodeling.Keywords: chronic obstructive pulmonary disease, proteinase with a disintegrin and a metalloproteinase domain-9, computed tomography, emphysema, airway remodeling

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