Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS)

Lung transplantation is increasingly employed as a therapy for patients with advanced lung
disease including cystic fibrosis, idiopathic pulmonary fibrosis or emphysema. Despite
significant short-term improvements in life quality and measures of lung function after lung
transplantation, long-term outcomes are disappointing primarily due to the development of a
condition of airway fibrosis known as bronchiolitis obliterans (BO). It is hypothesized that
aztreonam lysine for inhalation (AZLI) is a safe and effective treatment for declining lung
function in lung transplant recipients with early stage BOS. In order to test the
hypothesis, the investigators seek to establish the safety of AZLI in a two-center cohort of
30 lung transplant recipients with BOS treated intermittently for 5 consecutive study months
and determine if this treatment leads to improvement or stabilization of lung function. The
intervention will involve open label treatment with AZLI, in addition to usual transplant
care, administered for 3 intermittent courses, 28 days each, over a 5 month study period..
Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a
regular basis during study enrollment consistent with each center's usual standard clinical
care. Patients will have a baseline screening visit, one month and five month study visit..
The study will take two years to complete from the start of funding. After a start-up period
of 2 months, a total of 30 patients will be enrolled over 12 months across the two centers
(15 patients each at DUMC and UCLA). Each enrolled patient will complete 5 months of
intermittent therapy, and complete baseline, month 1 and month 5 visits. Over the next 6
months the study database will be finalized, statistical analysis will for primary and
secondary outcomes will be performed leading to the generation of either a study abstract or
manuscript.

Inclusion Criteria:

- Adult (18 or older at the time of transplant) male or female

- Cadaveric first lung transplant recipient, single or bilateral; or multi-organ lung
transplant recipient.

- Current FEV1 66-80% of posttransplant baseline FEV1, and meets all criteria for BOS 1
as defined by the International Society of Heart and Lung Transplantation.

- Onset of BOS 1 within twelve months of screening

Exclusion Criteria:

- Known allergy to aztreonam

- Retransplant

- Pediatric patients

- Live lobar transplant recipients

- Inability to provide informed consent.

- Patients with advanced BOS (grades 2,3) or established BOS >6 months

- Pregnant Women