Lung transplantation chronic rejection

Multiple studies assessed azithromycin in chronic lung disease, including non-CF bronchiectasis [9lS92, asthma [93 -] and chronic lung allograft rejection. Existing evidence was extensively reviewed for postlung transplant chronic rejection [94 ]. 

Neuringer IP, Chalermskulrat W, Aris R. Obliterative bronchiolitis or chronic lung allograft rejection a basic science review. J Heart Lung Transplant 2005 24 3-19. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Azuma H, Tilney NL. 1995. Immune and nonimmune mechanisms of chronic rejection of kidney allografts. J Heat Lung Transplant. 14 S136-S142. 

Pinderski LJ, Kirklin JK, McGiffin D, Brown R, et al. 2005. Multi-organ transplantation Is there a protective effect against acute and chronic rejection J Heart Lung Transplant. 24 1828-1833. 

Acute and chronic rejection are major problems compromising transplant and patient survival. Many studies indicate that aerosolized cyclosporin A is useful for reducing the risk of acute rejection. The lung concentrates and retains cyclosporin A better after inhalation [152,153]. A number in investigators have found that aerosolized cyclosporin reduces acute rejection in animals [154-157], and some studies suggest efficacy in treating acute [158] and chronic [159,160] rejection in human transplant recipients. 

Currently, since the safety and efficacy of SRL has not been established in liver or lung transplants, it is recommended that its use be avoided in these populations immediately following transplant. In contrast, limited data on the use of SRL in heart transplantation indicate benefit in reversing acute rejection in patients who do not respond to antilymphocyte therapy. Furthermore, SRL may slow the progression of vasculopathy, which may have an impact on chronic rejection and long-term patient survival after heart transplantation. ... 

Uvama T, Winter JB, Groen G, Wildevuur CRH, Monden Y, Prop J. Late airway changes caused by chronic rejection in rat lung allografts. Transplantation 1992 54 809-812. 

Matsumura Y, Marchevsky A, Zuo XJ, Kass RM, Matloff JM, Jorden SC. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation. Transplantation 1995 59 1509-1517. 

Winter JB, CleUand C, Gouw AS, Prop J. Distinct phenotypes of infiltrating cells during acute and chronic lung rejection in human heart-lung transplants. Transplantation 1995 59 63-69. 

Verleden GM, Buyse B, Delcroix M, et al. Cyclophosphamide rescue therapy for chronic rejection after lung transplantation. J Heart Lung Transplant 1999 18 1139-1142. 

Cahill BC, Somerville T, Karwande SW, et al. Early experience with sirolimus in lung transplant recipients with chronic allograft rejection. J Heart Lung Transplant 2003 22 169-176. 

Ussetti R, Caireno, MC, de Pablo A, et al. Rapamycin and chronic lung rejection. J Heart Lung Transplant 2004 23 917-918. 

Fig 2.2.9a-d. Bronchiolitis obliterans and pulmonary fibrosis. A 42-year-old man with a history of heart/lung transplantation for Eisenmenger syndrome 10 years ago, now with increasing shortness of breath, a, b Chest CT shows changes of end-stage bronchiolitis obliterans and pulmonary fibrosis secondary to chronic lung rejection. C, d Note typical anatomic configuration of heart transplantation performed with the atrial-atrial method. There is an increased space between the donor aorta and the recipient superior vena cava (arrow). Note the remnant of the donor superior vena cava (arrowhead)... 

Gastroesophageal reflux (GER) appears to be common in patients following lung transplantation, and may contribute to chronic allograft rejection. 

Against the bacterial modulation concept are a range of arguments that involve both mechanistic studies on inflammatory processes reported here and more circumstantial evidence derived from clinical studies. For example, in lung transplant, one phenomenon of chronic rejection of the graft is known as bronchiolitis obliterans. Around 40% of patients with this condition respond to treatment with azithromycin and detailed studies suggest that these are the sub-set of patients in which neutrophilia in the airway contributes to the apparent disease. Administration of azithromycin leads to fewer neutrophils in the airway and recovery of airway function. Other forms of bronchiolitis obliterans appear not to respond to azithromycin. Responses are obtained in the absence of clear infection and so in this example it is reasoned that the macrolide effect is an immunomodulatory one. ° ... 

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