Clinical lung and heart/lung transplantationSputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients: relation to tumor necrosis factor-α and interleukin-10
Section snippets
Patients
We entered 30 LTx patients into the study (80% males; mean age, 48 years; range, 18 to 64 years). Indications for transplantation were pulmonary emphysema (n = 13), idiopathic pulmonary fibrosis (n = 9), cystic fibrosis (n = 6), and others (n = 2). Of these, 16 patients had undergone single lung transplantation and 13 patients had undergone double lung transplantation. One patient had undergone single retransplantation after initial double-LTx. Immunosuppressive regimens post-transplantation
Transplant function
According to the International Society for Heart and Lung Transplantation consensus report,24 12 patients met the clinical criteria for chronic transplant rejection, whereas the other 18 had apparently regular graft function. Absolute and relative (% predicted) values of FEV1 and the ratio of FEV1/FVC were significantly lower in LTx patients with chronic rejection (Table I). Sputum cultures were positive for P cepacia in 1 patient with underlying cystic fibrosis, and for S aureus in another
Discussion
Chronic rejection is the major cause limiting overall prognosis of patients after lung transplantation. Transplant rejection is a complex inflammatory process that involves a variety of effector cells and mediators. This study reports the feasibility of using sputum induction to investigate lower respiratory tract inflammation in lung transplant recipients. Consistent with bronchoalveolar lavage and biopsy studies,21, 25 pronounced neutrophilia was present in the airway secretions of LTx
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Cited by (38)
The potential of biomarkers of fibrosis in chronic lung allograft dysfunction
2021, Transplantation ReviewsCitation Excerpt :In LTX patients, sputum MMP-9 and TIMP-1 levels were significantly higher compared to normal controls, with CLAD patients having the highest levels of MMP-9. In addition, the MMP-9/TIMP-1 ratio was high in patients with chronic rejection, suggesting an imbalance between MMP-9 and its inhibitor that may lead to aberrant extracellular matrix remodeling in the airways, activation of growth factors and cytokines and the induction of a profibrotic response as is characteristic of this MMP [43,45,46]. Importantly, a study by Hubner et al. reported a higher MMP-9/TIMP-1 ratio in patients with BOS and this ratio also correlated negatively with FEV1 in these patients [47].
The airway epithelium is a direct source of matrix degrading enzymes in bronchiolitis obliterans syndrome
2011, Journal of Heart and Lung TransplantationCitation Excerpt :As a result, we cannot exclude the possibility that the changes in MMP expression observed are due to time after transplant and not BOS development. This is unlikely, however, because other studies have not reported an effect of time after transplant on BAL or sputum MMP activity.3,5,31 Another limitation is the lack of healthy adult controls.
Attacking the multi-tiered proteolytic pathology of COPD: New insights from basic and translational studies
2009, Pharmacology and TherapeuticsTissue inhibitor of metalloproteinase-1 moderates airway re-epithelialization by regulating Matrilysin activity
2008, American Journal of PathologyCitation Excerpt :Indeed, the concept that epithelial damage promotes remodeling and fibrosis is not limited to OB and has been linked to other pulmonary diseases such as idiopathic pulmonary fibrosis and asthma66–69 as well as fibrotic diseases of the liver and kidneys.70–72 TIMP-1 expression increases in the lung allograft of patients with BOS/OB.39–42 Increased lung expression of TIMP-1 is also associated with the onset of OB42 and contributes to the pathogenesis of airway fibrosis in a mouse model of OB.44
Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome
2007, American Journal of TransplantationMatrix metalloproteinase induction in post-transplant obliterative bronchiolitis
2005, Journal of Heart and Lung Transplantation