The Longitudinal Impact of Respiratory Viruses on Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation (The RV-BOS Study)

Inclusion Criteria:

   - Allogeneic HCT recipients with any indication, graft source, donor type, or
   conditioning regimen

   - Age 8 and older

   - COHORT 1 Inclusion criteria: One or more of the following clinical scenarios that
   encompass increased risk for BOS:

      1. A diagnosis of cGVHD as per NIH criteria through 5 years of diagnosis.

      i. New diagnosis of cGVHD within 3 months.

      ii. A diagnosis of cGVHD > 3 months < 5 years with a new FEV1 decline of >10% in
      absolute compared with prior 2 years PFT.

      iii. A recent documented respiratory infection of any etiology that has been
      clinically managed and stabilized or improving as determined by a clinician,
      within 8 weeks.

      iv. Progression of flare of chronic GVHD requiring an alteration in therapy as
      determined by a clinician, within 3 months.

      2. At Day 80 evaluation. D80 designates a time frame D70-120 posttransplant to
      account for local variations in posttransplant care.

      i. FEV1 decline of 10% in absolute values compared with pretransplant baseline.
      ii. Documented posttransplant RVI. iii. Lower respiratory tract disease (LRTD) of
      any etiology.

   - COHORT 2 inclusion criteria: Newly diagnosed BOS within 6 weeks of clinical
   recognition. This may include the following scenarios:

      1. "Early BOS", ie patients with new airflow decline and obstruction, not yet
      meeting the FEV1 cut-off of < 75% predicted by FEV1, in the absence of other
      etiologies as determined by clinical investigations including chest imaging and
      microbiologic studies.

      2. NIH-defined BOS:

      i. FEV1 < 75% predicted, with a decline in absolute FEV1 > 10% compared to
      pretransplant baseline or within the prior 2 years. Absolute decline in FEV1
      should remain >10% after bronchodilator response.

      ii. FEV1/FVC or FEV1/VC <0.7, or Lower Limit of Normal as per accepted reference
      standards. Reference standards may include National Health and Nutrition
      Examination Survey III or Global Lung Initiative.

      iii. Absence of an alternative diagnosis, including COPD exacerbation, asthma,
      and active respiratory tract infection, as determined by appropriate clinical
      investigationsthat may include chest imaging, microbiologic cultures, and/or
      bronchoscopy.

      iv. One of two supportive features of BOS:

         - a. Evidence of air trapping by PFTs: RV>120%, or elevated RV/TLC (>20% of
         predicted value)

         - b. High resolution chest CT with inspiratory and expiratory cuts that show
         findings that are consistent with small airways disease including (but not
         exclusive of) air trapping, bronchial wall thickening, or bronchiectasis.

      3. BOS with atypical spirometric pattern

      i. FEV1 <80%, with a preserved FEV1/FVC ratio (>0.7) and TLC >80% in the absence
      of other clinically determined lung disease.

      4. Clinical or suspected diagnosis of BOS not otherwise meeting above criteria.

   - Patient should have an Android or iOS-based smartphone with reliable access to Wi-Fi
   for data to be transmitted electronically. Android smartphones should have a software
   version of 4.0 or higher; iOS phones should have a version of 8.0 or higher.

   - Patient should be willing and able to communicate electronically in English.

Exclusion Criteria:

   - Life expectancy < 2 years.

   - Diagnosis of active hematologic relapse or malignancy requiring active treatment that
   will affect that patient's ability to comply with study procedures.

   - Patient should not have a clinically acute active lower respiratory tract infection or
   a clinically acute active noninfectious respiratory condition (i.e. COPD exacerbation,
   pleural effusion) at the time of enrollment. However, patient may become eligible once
   these conditions have stabilized or resolved as noted above.

   - Inability or unwillingness to perform the study procedures, most of which are
   performed at home.

   - Lack of a personal iOS or Android smartphone.

   - Inability or unwillingness to communicate electronically.