Postulated mechanism for why early-onset ACS in children with sickle-cell anaemia younger than 4 years is associated with both short-term and long-term acute lung morbidity (ACS, asthma, or both). The initial ACS event results in airway inflammation and hyper-responsiveness, which predispose the airways to narrowing from a second hit, either a repeat viral infection (young children have about six viral infections a year), exposure to an environmental irritant (eg, cigarette smoke), or a history of atopy with exposure to an aeroallergen to which there is sensitivity. A second event then leads to a sequence of events that result in a repeat severe vaso-occlusive episode. ACS=acute chest syndrome. HbS=haemoglobin S.