Inclusion Criteria:
* Age \> 18 years old
* Recipient of a double pulmonary allograft at least 12 months before study entry
* Subjects with clinically diagnosed CLAD-BOS phenotype (all 3 required)
* BOS defined as screening FEV1 between 85-51% of the baseline as defined by the 2 highest FEV1 measures at least 3 weeks apart.
* Diagnosis within 12 months of screening visit.
* FEV1 decline is persistent as defined by decline sustained for \> 30 days.
* Currently receiving Standard Immunosuppression. This is defined as a combination of 3 medications including Prednisone, Mycophenolate or Azathioprine, and Tacrolimus or Cyclosporine. The dosing should be stable for 4 weeks prior to screening.
* Absence of oral sirolimus or everolimus treatment for at least 4 weeks prior to screening based on the half-life and resolution of the tissue effects
* Stable enough to enable routine post-transplant bronchoscopy with BAL and biopsy when indicated
* Capable of understanding the purposes and risks of the study
* Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
* Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry
* Women of childbearing potential if sexually active must agree to using highly effective contraception during study and for 90 days after discontinuation of study treatment
* Women of childbearing potential must refrain from breast feeding or donating eggs for the duration of the study and for 90 days after the last dose of study treatment
* Male participants must agree to use a condom during sexual contact with a female of childbearing potential while participating in the study and for 90 days following discontinuation of investigational product use
* Male participants must refrain from donating sperm for the duration of the study and for 90 days after the last dose of study treatment
Exclusion Criteria:
* Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
* Patients with re-transplantation or currently listed for re-transplantation
* Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (CLAD - RAS phenotype, see Protocol Specific Definition), etc.
* Patients with acute antibody-mediated rejection at Screening. In this context, clinically stable patients (as judged by the Investigator) with detectable donor-specific antibodies (DSA) levels at the Screening Visit are eligible for the study
* Active acute bacterial, viral, or fungal infection that has not successfully resolved in at least 4 weeks prior to the Screening Visit. Patients with chronic infection or colonization who are clinically stable as per judgement of the investigator are eligible.
* Mechanical ventilation within 12 weeks prior to the randomization
* Patient has baseline resting oxygen saturation of \< 89% on room air or use of supplemental oxygen at rest at screening
* Evidence of functional airway stenosis (i.e., bronchomalacia/ tracheomalacia, airway stents, or airways requiring balloon dilatations to maintain patency) with onset after the initial diagnosis of BOS and ongoing at Screening and/or Baseline Visit
* Known hypersensitivity to sirolimus or everolimus
* Currently enrolled in another investigational trial for obstructive chronic lung allograft dysfunction (BOS)
* Patients with chronic renal failure, defined as serum creatinine \> 2.5 mg/dL at screening, or requiring chronic dialysis
* Patients with liver disease and serum bilirubin \> 3-fold upper limit of normal range or transaminases \> 2.5 upper limit of normal range
* Patients with active malignancy within the previous 2 years, including post-transplant lymphoproliferative disorder, except for treated, localized basal and squamous cell carcinomas
* Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 6 months. This does not include minor surgical procedures for localized skin cancer.
* History of severe allergic reaction to lactose (patients with lactose intolerance are eligible)
* Patients with uncontrolled hypertension
