Bronchopulmonary dysplasia (BPD), cur-rently the most common chronic respi-ratory disease in infants, is a multifacto-rial disease secondary to genetic (1) andenvironmental factors (chief among thembeing exposure to invasive mechanical ven-tilation, ante- and postnatal infections,and hyperoxia) (2, 3). It is estimated thatapproximately 10,000–15,000 new cases ofBPD occur each year in the United States,of which 97% occur in infants with birthweights <1250g (3). Over the last decade,the incidence of BPD has been reportedvariably to have decreased (4), remainedthe same (5), or even increased slightly(3, 6, 7). However, there is uniform agree-ment that BPD is associated with signif-icant resource utilization and increasedcosts (4,8).While studies assessing the eco-nomic burden of BPD are mostly restrictedto their initial hospitalization in neona-tal intensive care units (4, 8), this is achronic lung disease with significant pul-monary and neurodevelopmental seque-lae (3, 9, 10) that impacts healthcare costsinto the pediatric age group (11, 12) andwouldbeexpectedtocontinuetodosointoadulthood (13).Given the above data, novel effectivedrug therapies for the prevention of BPDwould potentially make a significant dif-ference in the health and costs for pre-maturely born children. A recent work-shop conducted under the auspices of theNational Heart Lung and Blood Instituteof the National Institutes of Health onthe primary prevention of chronic lungdiseases focused on BPD (14). In termsof “promising near-term opportunities forprimary BPD prevention research,” specif-ically, “clinical research priorities and spe-cific clinical trials for BPD prevention,” itwas disappointing to note that only twospecific drugs were named: caffeine andinhaled nitric oxide (iNO).While caffeine has been associated withimprovementinBPD(15)andneurodevel-opmental outcomes (16) [unfortunately,not sustained at 5years of age (17)], stud-ies fine-tuning the timing of initiation andduration of use of this drug would beuseful. This is important given the factthat the mechanism of action in termsof the pulmonary effects in the develop-ing lung is not currently understood andtoxicity concerns have been raised in ananimal study (18). Despite a large num-ber of infants being studied in random-ized clinical trials (RCTs), iNO has notbeen consistently found to be beneficial inpreventing BPD and is currently not rec-ommended for such treatment (19, 20).It is therefore critical that for both caf-feine and iNO, given past experience, sub-group targeted therapy (21) should betested in future RCTs. Such targeted sub-groups could be on the basis of genotypeor phenotype (for e.g., small for gesta-tional age infants) criteria. Assessment ofgenotypes would be a useful technique toidentify specific populations most likelyto benefit from such a targeted approach,which would incorporate the not insignif-icant effects of the genetic contribution toBPD (1, 22–24).On searching the