View clinical trials related to Bronchiolitis, Proliferative.
Filter by:Background: - Bronchiolitis obliterans or bronchiolitis obliterans syndrome is a lung disorder that occurs as a complication of either lung transplantation or bone marrow/blood stem cell transplantation. One of the complications of transplant is the occurrence of graft versus host disease (in hematopoietic stem cell transplants) and host versus graft disease (in lung transplantation). In these diseases, the cells attack the lungs and cause irreversible small airway fibrosis referred to as bronchiolitis obliterans syndrome. When a patient develops fibrosis of the lungs or bronchioles, the lungs no longer work properly, which causes difficulties with breathing that lead to a diminished quality of life and an increased risk of death. Treatment typically involves immunosuppressive therapy such as oral cyclosporine or steroid therapy, but these treatments are only marginally effective and can cause significant toxicities and increase the risk of infections. Inhaled cyclosporine (CIS) achieves higher concentrations of cyclosporine in the lungs and lower concentrations of cyclosporine in the blood than oral cyclosporine. Therefore, it could have advantages over conventional oral immunosuppressive therapies used to treat this disorder. Researchers are interested in testing whether inhaled cyclosporine therapy could be used as a safe and effective treatment for bronchiolitis obliterans or bronchiolitis obliterans syndrome occurring after bone marrow/blood stem cell or lung transplants. Objectives: - To evaluate whether inhaled cyclosporine (CIS) can improve or stabilize lung function and quality of life in individuals with bronchiolitis obliterans. Eligibility: - Individuals between 10 and 80 years of age who have been diagnosed with bronchiolitis obliterans or bronchiolitis obliterans syndrome after blood or lung transplants. Design: - Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, lung function tests, imaging studies, bronchoalveolar lavage samples, and quality of life questionnaires. - Participants will take cyclosporine inhalation solution through a nebulizer. The nebulizer generates a mist of cyclosporine inhalation solution (CIS), which is then breathed in through a mouthpiece. The process takes approximately 20 minutes. The solution will be provided in single-use vials. - Participants will continue to take all medications for post-transplant care as required by their doctor and the study researchers. Attempts will be made to reduce the doses and types of immunosuppressants given to participants on the study, as long as the treatment continues to produce improved or stable lung function. - Participants will have study visits every 3 weeks with blood and urine tests, lung function tests, and imaging studies. Participants will undergo repeat bronchoalveolar sample at week 9 and 18. Participants will also complete quality of life questionnaires as directed. Treatment will continue for a minimum of 18 weeks, followed by a final follow-up visit 2 weeks after the end of the study. - Participants who benefit from the inhaled cyclosporine (CIS) may continue to receive further therapy with inhaled cyclosporine at the end of the study by participation in a separate study extension.
Bronchiolitis Obliterans (BO) is an obstructive lung disease that can affect individuals that have undergone a lung or hematopoietic stem cell transplant. BO has been studied most extensively in lung transplant recipients, where it is considered to represent chronic lung rejection. It is the leading cause of death after lung transplant, with mortality rates up to 55 percent. In hematopoietic stem cell transplantation, BO is thought to be a manifestation of chronic graft-vs-host disease (GVHD). Up to 45 percent of patients undergoing hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function. Conventional therapy for patients who develop BO consists of augmentation of systemic immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated with deleterious consequences including increased risk of infections and decreased graft-versus tumor/leukemia effects. Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been shown to improve overall survival and chronic rejection-free survival in lung transplant patients. These findings suggest targeted delivery of immunosuppressive therapy to the diseased organ warrants further investigation as this may minimize the morbidity associated with systemic immunosuppression. However, there currently exists limited data regarding the overall efficacy of inhaled cyclosporine to treat established BO following lung transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of BO following hematopoietic stem cell transplantation. Here, we propose to evaluate the long-term safety and efficacy, of inhaled CIS for the treatment of BO. Enrollment will be offered to subjects who have completed the end of study (week 18 visit) for the initial protocol (Phase II Trial of CIS in lung transplant and hematopoietic stem cell transplant recipients for treatment of Bronchiolitis Obliterans) and who have shown evidence of benefit (either an improvement or stabilization) in BO/BOS with CIS treatment. Clinical parameters, including pulmonary function tests, will be measured in addition to laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with extended treatment with CIS will be recorded. The primary objective is to provide long-term safety and efficacy data for the use of CIS in hematopoietic transplant patients and lung transplant patients with established BO. Secondary objectives include investigation of the inflammatory pathways that lead to chronic BO and ascertainment of the long term anti-inflammatory effects of this CSA preparation ex vivo and in vivo. Primary endpoint is the efficacy of extended use CIS for BO/BOS. Secondary endpoints include the toxicity profile (adverse events), improvement in high resolution chest CT images, results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers of inflammation, and functional capacity measurements using a six-minute walk test.