Small airways dysfunction in long-term survivors of pediatric stem cell transplantation

Chronic graft-versus-host disease (cGvHD) in the lungs is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Pulmonary cGvHD is initiated in the peripheral airways, and diagnosis may be delayed by low sensitivity of standard pulmonary function tests. Multiple breath nitrogen washout (MBWN2 ) is a promising, sensitive method to assess small airways function. This is the first report on MBWN2 in survivors of pediatric HSCT.

This cross-sectional study undertaken 3-10 years post-HSCT, included 64 patients and 64 matched controls who all performed spirometry, whole-body plethysmography and MBWN2 . From MBWN2 the lung clearance index (LCI) and indices reflecting ventilation inhomogeneity arising close to the acinar lung zone (Sacin ) and in the conductive airway zone (Scond ) were derived. Subjective respiratory morbidity was assessed using the St. George Respiratory Questionnaire.

LCI, Sacin , and Scond were significantly higher in HSCT-patients compared with controls. Despite few reported symptoms and normal forced expiratory volume in 1 sec (FEV1 ) in 91%, LCI, Scond , and Sacin were abnormal in 34%, 52%, and 25% of HSCT-patients, respectively. LCI and Scond correlated weakly with spirometric findings in HSCT-patients, but not in controls. Scond was abnormal in 82% (9/11) of patients with evidence of cGvHD, and was associated with cGvHD in the multivariate analysis (r(2)  = 0.26, P = 0.001).

Small airways dysfunction as measured by MBWN2 was a common finding at long term follow-up of children after allogeneic HSCT and was associated with cGvHD. The majority of these subjects had normal spirometric values and did not report any respiratory symptoms. Prospective studies are required to evaluate the long term clinical consequences of these signs of small airway disease and the value of MBWN2 as an early marker of pulmonary cGvHD.