Amending NIH Consensus Criteria for the Clinical Diagnosis of Bronchiolitis Obliterans After HSCT

Bronchiolitis obliterans (BO) after HSCT is a rare and morbid manifestation of cGVHD. Although lung biopsy is the gold standard for diagnosis, the high complication rate restricts its use. There is a lack of consensus in the literature concerning the diagnostic criteria using non-invasive modalities. Thus, the NIH cGVHD consensus project developed a definition for BO after HSCT based on clinical characteristics of BO after lung transplant. This definition required for non-pathologic diagnosis: a) Absence of infection, b) presence of another cGVHD sign, c) FEV-1<75% and d) all 3 parameters to confirm obstruction: 1) FEV1/FVC <0.7, 2) RV> 120%, and 3) CT findings (table). To explore the sensitivity of these criteria, we evaluated this definition in a group of patients with diagnoses of cGVHD and BO (corroborated by NIH pulmonologists). Twenty-four patients were identified; 1 was excluded for relapse and 1 for lack of full PFTs. We then analyzed pulmonary and radiographic parameters of these 15 clinically identified cases of BO and 7 biopsy proven cases. Only 18% (4/22) of patients met the NIH consensus definition for a clinical diagnosis of BO, all of which had an FEV1< 55% suggestive of severe disease. While the majority of the total had FEV1/FVC<0.7, using the slow vital capacity (FEV1/SVC) enhanced sensitivity, capturing patients with airways that collapse early, artificially lowering the FVC.Tabled 1NIH Consensus BO Clinical Definition Components% of Patients Meeting Each Individual Criteria with Biopsy Proven BO n=7% of Patients Meeting Each Individual Criteria with Clincal BO n=15Amended NIH Consensus BO Clinical Definition Components% of Patients Meeting Each Individual Criteria with Biopsy Proven BO n=7% of Patients Meeting Each Individual Criteria with Clinical BO n=15Absence of Infection100%100%Absence of Infection100%100%Another sign of cGVHD100%100%Another sign of cGVHD100%100%FEV1<75% predicted100%100%FEV1<75% predicted100%100%FEV1/FVC< 0.771%67%FEV1/SVC71%73%RV>120%29%27%RV>120%57%60%CT: air trapping or bronchiectasis80%75%CT: air trapping80%75%TOTAL Patients Meeting All Clinical Criteria29%13%TOTAL Patients Meeting All Clinical Criteria86%100% Open table in a new tab We then evaluated the patients that did not meet the new ratio criteria (FEV1/SVC<0.7); all (6/6) had evidence of severe restriction from scleroderma or myositis, thus masking the ratio evidence of obstruction. Because of their restrictive disease, the total lung capacity (TLC) was decreased, also artificially lowering the RV. When RV/TLC>120% of predicted was used with RV>120% predicted, 5/6 of these could be captured as BO and all had air trapping confirmed on expiratory CT. Therefore, we amended the definition of BO to confirm obstruction by either: 1) FEV1/SVC < 0.7 OR air trapping on CT with RV or RV/TLC > 120%. Using this amended definition, all but 1 case (biopsy proven) of our cohort could be captured clinically, increasing our sensitivity from 18% to 95%. We therefore present a modification of the NIH consortium criteria that our data suggests enhances the sensitivity of this test in our cGVHD population. These criteria will require further validation for integration into future trials.