ABSTRACT
These are a rare and disparate group of conditions; even specialist centres see less than 10 cases/year in total; and many are fatal in early life (1). So what is the relevance across the wider age spectrum? Mutations in the surfactant protein-(Sp)-C gene provide the most graphic illustration of the interactions between genetics, and developmental and environmental processes, and why we can no longer operate in developmental silos. The same gene mutation, in the same family, can present as a pulmonary alveolar proteinosis-like picture in newborns, and usual interstitial pneumonia (UIP, a condition unknown in children) in adults (2); furthermore, nearly 50% of SpC children present as slowly resolving respiratory syncytial virus (RSV) infection (3), and there are in vitro data showing that SpC mutation cells are especially vulnerable to the cytotoxic effects of RSV (4). Similarly, the same Adenosine triphosphate binding cassette subfamily A member 3 (ABCA3) mutation in the same family may have very differing clinical courses (5), and ABCA3 mutations also confer vulnerability to the effects of RSV (6). Respiratory bronchiolitis associated ILD and isolated Langerhans cell histiocytosis are both diseases of adult smokers, as may be DIP (7); all three are seen in children passively exposed to tobacco smoke (8–10).
