• The occurrence of BOS grade 0p through 3 in lung transplant recipients at 2 years after randomization [ Time Frame: From study initiation through 2+ years after randomization ] [ Designated as safety issue: No ]
• Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization [ Time Frame: From study initiation through 2+ years after randomization ] [ Designated as safety issue: No ]
• All cause mortality [ Time Frame: From study initiation through 2+ years after randomization ] [ Designated as safety issue: No ]

A Phase III, multi-center, randomized, controlled study designed to demonstrate the efficacy and safety of Cyclosporine Inhalation Solution (CIS)in improving survival and preventing bronchiolitis obliterans syndrome (BOS) when given prophylactically to lung transplant recipients in addition to their standard immunosuppressive regimen.

• Active Comparator: CIS in addition to standard immunosuppressive regimen.
• No Intervention: Standard of care (SOC) therapy for lung transplant recipients

• Burkart GJ, Smaldone GC, Eldon MA, Venkataramanan R, Dauber J, Zeevi A, McCurry K, McKaveney TP, Corcoran TE, Griffith BP, Iacono AT. Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Pharm Res. 2003 Feb;20(2):252-6.
• Iacono AT, Smaldone GC, Keenan RJ, Diot P, Dauber JH, Zeevi A, Burckart GJ, Griffith BP. Dose-related reversal of acute lung rejection by aerosolized cyclosporine. Am J Respir Crit Care Med. 1997 May;155(5):1690-8.
• Keenan RJ, Iacono A, Dauber JH, Zeevi A, Yousem SA, Ohori NP, Burckart GJ, Kawai A, Smaldone GC, Griffith BP. Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients. J Thorac Cardiovasc Surg. 1997 Feb;113(2):335-40; discussion 340-1.
• Iacono A, Dauber J, Keenan R, Spichty K, Cai J, Grgurich W, Burckart G, Smaldone G, Pham S, Ohori NP, Yousem S, Williams P, Griffith B, Zeevi A. Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine. Transplantation. 1997 Jul 27;64(2):263-9.
• Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50.
• Iacono AT, Corcoran TE, Griffith BP, Grgurich WF, Smith DA, Zeevi A, Smaldone GC, McCurry KR, Johnson BA, Dauber JH. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J. 2004 Mar;23(3):384-90.
• Iacono AT, Keenan RJ, Duncan SR, Smaldone GC, Dauber JH, Paradis IL, Ohori NP, Grgurich WF, Burckart GJ, Zeevi A, Delgado E, O'Riordan TG, Zendarsky MM, Yousem SA, Griffith BP. Aerosolized cyclosporine in lung recipients with refractory chronic rejection. Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1451-5.

Inclusion Criteria:

• A recipient of a single or double lung transplant (including heart-lung transplant)
• Age 18 years or older
• Able to produce a forced expiratory volume in one second (FEV1) of greater than one liter at randomization
• Eligible subjects must be enrolled within 70 days after receiving a lung transplant
• Clinical status sufficiently stable to enable routine post-transplant bronchoscopy with bronchoalveolar lavage (BAL) and chest X-ray (or equivalent i.e., chest computerized tomogram (CT)) prior to screening

Exclusion Criteria:

• Lung re-transplantation
• Documented allergy to propylene glycol and/or cyclosporine
• Documented respiratory or anastomotic infections unless on appropriate antimicrobial therapy with evidence of clinical response
• Women who are pregnant, wishing to become pregnant, or unwilling to use appropriate birth control to avoid becoming pregnant
• Women who are breastfeeding
• Clinically significant bronchial stenosis unresponsive to dilation and/or stenting
• Malignancies diagnosed within one year prior to screening (with the exception of non-melanomatous skin cancers)