Aerosolized cyclosporine in lung recipients with refractory chronic rejection.

Abstract

This study evaluated aerosolized cyclosporine as rescue therapy for lung transplant recipients with unremitting chronic rejection. Nine patients with histologic active obliterative bronchiolitis and progressively worsening airway obstruction refractory to conventional immune suppression received aerosolized cyclosporine. Improvement in rejection histology was seen in seven of nine patients. We compared the changes in the FVC and FEV1 over time using linear regression analysis in these seven histologic responders and nine historical control patients. During the pretreatment period for both the experimental and control groups, the FVC and FEV1 declined at comparable rates. After aerosolized cyclosporine there was stabilization of pulmonary function, whereas in the controls there was continued decline. Cyclosporine blood levels were less than 50 ng/ml 24 h after an aerosolized dose of 300 mg in five patients receiving oral tacrolimus. Nephrotoxicity, hepatotoxicity, and a greater than expected rate of infection was not observed. This study suggests that aerosolized cyclosporine is safe and may be effective therapy for refractory chronic rejection in lung transplant recipients.

Immunosuppressive therapy after human lung transplantation

“…This has led to the concept of delivering these medications directly to the lower respiratory tract by aerosol inhalation, thereby increasing drug delivery while decreasing systemic drug exposure. In this regard, IACONO et al [108] have reported stabilisation of pulmonary function in seven of nine patients with chronic rejection after treatment with inhaled CsA. However, aerosolised CsA has been consistently unavailable for other investigators and there are no further data at the present time.…”

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics

“…Animal studies of lung transplantation demonstrate that inhaled cyclosporine can achieve high graft concentrations with minimal toxicity, 82,83 and these findings have been supported by open label trials in human transplant subjects. 84,85 An RCT of inhaled cyclosporine versus placebo in 58 subjects after lung transplantation demonstrated that whereas there was no improvement in rates of acute rejection, survival and chronic rejection-free survival were significantly greater with inhaled cyclosporine relative to placebo. 86 Nebulized cyclosporine has also been evaluated for safety and pharmacokinetics in healthy controls and asthma subjects.…”

Lung Diseases - Selected State of the Art Reviews

“…Vasculitis Dowd et al, 1995;Esnault, 1997;Griffith et al, 1996Panniculitis Chowdhury et al, 2002Gross et al, 2009;Kjus et al, 2002;Smith et al, 1987;Valverde et al, 2008Fibromyalgia Ablin et al, 2009Blanco et al, 2004;Blanco et al, 2010Asthma Blanco et al, 2008Blanco et al, 2011;Eden et al, 1997Pancreatitis Rabassa et al, 1995Needlham & Stockley, 2004Renal Szönyi et al, 2006Ting et., 2008Diabetes Kalis et al, 2010Lisowska-Myjak et al, 2006;Cancer Li et al, 2011;Lindor et al, 2010;Topic et al, 2011Rheumatoid arthritis Grimstein et al, 2010Grimstein et al, 2011Atherosclerosis Stakisaitis et al, 2001Talmud et al, 2003;Acute anterior uveitis Fearnley et al, 1988;Saari et al, 1986Chronic rhinosinusitis Kilty et al, 2008Maune et al, 1995 (Cantin et al, 2002b). According to their data, the site-specific conjugation with either 20 or 40 kD PEG at Cys 232 of nonglycosylated r- 1 -PI (human) results in an active inhibitor with extended in vivo stability.…”

“…Most present strategies rely on augmenting immunosuppression with the use of corticosteroids, cyclosporine, methotrexate, etc. (Date et al 1998;Dusmet et al 1996;Iacono et al 1996) These, however have been met with little success. The majority of existing treatment methods rely on unproven, anecdotal evidence with few multi-center, randomized, controlled trials.…”