The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia

Abstract

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management.

Figure 1. Relationship between asthma and increased rate of pain events (A) and acute chest syndrome (B) in children with sickle-cell anaemia

Overall incidence rate of painful events (A) is higher in children with asthma (1·39 events per patient-year) than in those without asthma (0·47 events per patient-year; p<0·001). Overall incidence rate of acute chest syndrome events (B) is higher in children with asthma (0·39 events per patient-year) than in children without asthma (0·20 events per patient-year, p<0·001). *Line segments are point-wise exact 95% CI. Reproduced with permission of the American Haematology Society.

Figure 2. Proposed pathophysiology in children with sickle-cell anaemia with early-onset ACS

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.