NHANES III equations enhance early detection and mortality prediction of bronchiolitis obliterans syndrome after hematopoietic SCT

Abstract

Bronchiolitis obliterans syndrome (BOS) is a serious complication of chronic GVHD (cGVHD) following HSCT (hematopoietic SCT). The clinical diagnosis of BOS is based on pulmonary function test (PFT) abnormalities including: FEV1<75% predicted and obstructive FEV1/VC ratio, calculated using reference equations. We sought to determine if the frequency of clinical diagnoses and severity of BOS would be altered by using the recommended NHANES III vs older equations (Morris/Goldman/Bates, MGB) in 166 cGVHD patients, median age 48 (range: 12–67). We found that NHANES III equations significantly increased the prevalence of BOS, with an additional 11% (18/166) meeting diagnostic criteria by revealing low FEV1 (<75%) (P<0.0001), and six additional patients by obstructive ratio (vs MBG). Collectively, this led to an increase of BOS incidence from 17 (29/166) to 29% (41/166). For patients with severe BOS, (FEV1<35%), NHANES III equations correctly predicted death 71.4% vs 50% using MGB. In conclusion, the use of NHANES III equations markedly increases the proportion of cases meeting diagnostic criteria for BOS and improves prediction of survival.

Prognostic role of FEV1 for survival in bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation

“…Therefore, we believe that our present findings could be applied to patients with relatively severe BOS. Indeed, Williams et al recently reported that an FEV 1 < 35% of predicted was a significantly predictor of mortality in patients with BOS . Our current findings are also consistent with studies in COPD, in which FEV 1 is one of the most established predictors of mortality , particularly in patients with very severe airflow obstruction .…”

“…Considering that FEV 1 is one of the most important prognostic markers of COPD , we speculated that FEV 1 may be a predictor of survival in patients with BOS after HSCT, as both BOS and COPD are characterized by airflow obstruction. However, data to support this hypothesis are limited . Our current study findings suggest that FEV 1 can be used to predict the clinical course of BOS.…”

How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

“…Patient 1 would have met criteria for BOS by PFTs alone using current definitions using National Health and Nutrition Examination Survey equations. 13 Similarly, elderly individuals may have appropriate age-related decline in FEV1 to ,0.7 and not de facto meet criteria for obstruction. Finally, the slow VC may now be used rather than FVC, as some BOS patients require slow exhalation to reveal full VC due to early airway collapse with the forced expiratory maneuver.…”

“…The slope also removes any influence of different PFT equations, which can significantly alter FEV1% predicted (up to 27%). 13 In addition to quickly revealing FEV1 changes, the rate of decline can be compared interpatient to compare disease severity and intrapatient to evaluate the success of therapies. Notably, for pediatric patients, the necessity of growth is important to include, thus it is best to evaluate the percentpredicted slope for prognosis (showing sufficient recruitment of lung for growth).19 For children with pneumothorax limiting PFTs, 6-minute walk assessment can be a good surrogate for progression in the absence of other cGVHD manifestations that impair mobility.…”

MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

“…This is mainly due to chronic allograft dysfunction, manifesting as OB, characterized histologically by inflammation and fibrosis of small airways. In BMT recipients, the incidence of OB has been reported to be as high as 29% with increased risk of mortality and is associated with chronic graft-versus-host disease (GVHD) [2] , [3] . After transplant, the host immune system is activated by exposure to allogeneic tissue antigens, resulting in an inflammatory cascade with alloimmune and non-alloimmune dependent factors contributing to the response.…”