Birgitta Versluijs

56 Discussion our cohort, compared with at least 60 days in previous studies. Progression to LRTI might be expected in patients with RV infection early after transplantation, because of poor immune status, but this was not seen. In our opinion, it is more likely that the mo- ment of immune recovery defines the onset of symptoms. What we define as IPS in this study (ie, symptoms after a period of quiescent RV infection) might have been reported in other stud-ies as progressive viral pneumonia, with symptoms occurring at the onset of RV infection later after HSCT, when some immune recovery has already occurred. The reported incidence of IPS after HSCT ranges from 2% to 15% of patients, 2,4,25,26 and that of BOS ranges from 0% to 26%. 1,4,27,28 Most reported data are from adult studies. The combined incidence of allo-LS in our cohort of 27.3% is comparable to that reported in the literature. Our incidence of IPS is relatively high, most likely because our cohort included a high number of early RV-positive patients. We found a strong association between RV infection and the development of allo-LS. To the best of our knowledge, this is the first report of such a strong association between RV infection and life-threatening allo-LS.Earlier, Erard et al. 17 described a relationship be- tween RV infection during the first 100 days after HSCT and a decline in airflow leading to increased overall mortality. The decline in airflow was detected immediately after in- fection and did not return to baseline values, suggesting sustained airway inflammation leading to permanent loss of lung function. Pulmonary disease was much more severe in our cohort compared with the cohort of Erard et al. 17 This discrepancy can be explained by the early moment of RV infection, when immune recovery has not yet occurred and the persistent RV likely causes more tissue damage, ultimately resulting in a stronger inflammatory response. The absence of immunity at the time of primary RV infection also might explain the absence of an immediate decline in clinical lung function. Pulmo- nary function deteriorated only after at least 2 weeks after RV infection, when the first signs of immune recovery were evident. It would be interesting to routinely perform PFTs earlier after HSCT, but for reasons of hygiene and patient comfort, we decided not to do this in the present study. Most previous studies have found an association between the presence of GVHD and the development of allo-LS. 1,2,25,29 In those studies, aGVHD was associated with IPS, but other risk factors, including conditioning regimen and infection, might have been in- volved as well. cGVHD is considered an important risk factor for BOS in adults. Allore- active T cells, in the context of aGVHD or cGVHD, play an important role in BOS. 29 BOS is also seen in the absence of cGVHD in 7%-18% of patients, however. 27 This percentage may be different in children, who are less susceptible to cGVHD. 30 Our finding that aGVHD grade II-IV in other organs has a protective effect on the development of allo-LS does not necessarily contradict these results. Like aGVHD, allo-LS is a manifestation of alloimmunity. We speculate that the apparent protective effect of aGVHD reflects the 3