18th February 2025

Overview of pulmonary complications of sickle cell disease

Sickle cell disease (SCD) refers to a group of haemoglobinopathies where the sickle mutation is co-inherited with another mutation affecting the other beta globin subunit in haemoglobin (Hb), causing reduced or absent normal beta globin production. Sickle cell anaemia (SCA) is the term used when someone is homozygous for the sickle mutation, resulting in the formation of the HbS (sickle haemoglobin) molecule. The HbS molecule is much less soluble than normal HbA when deoxygenated, causing red cells to deform (sickle). The complications seen in SCD occur as a result of this sickling, such as vaso-occlusive events, haemolysis and pulmonary complications such as acute chest syndrome and pulmonary hypertension (PH).

The pulmonary complications of SCD are particularly important because they are a major cause of morbidity and mortality, with acute chest syndrome and pulmonary hypertension having the highest associated mortality in these populations.

There are numerous pulmonary complications seen in SCD:

• Acute chest syndrome (discussed in detail later)
• Asthma – asthma is much more common in people with SCD, with up to 70% of children with SCD having airway hypersensitivity. Asthma is more common in children with a history of acute chest syndrome and children with asthma have a higher incidence of acute chest syndrome.
• Sleep disordered breathing – increased incidence in people with SCD, and is commonly due to obstructive sleep apnoea, associated with nocturnal hypoxaemia. These are linked with increased risk of vaso-occlusive events, cardiovascular complications and neurological disease.
• Pneumonia – more common in people with SCD. Common causative organisms include Chlamydophila pneumoniae and Mycoplasma pneumoniae. They’re also at increased risk of infection from encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae as they are functionally asplenic.
• Pulmonary venous thromboembolism – SCD is a hypercoagulable state, leading to increased risk of thromboembolisms
• Pulmonary hypertension – occurs in 6-11% of people with SCD and is an independent risk factor for mortality
• Chronic dyspnoea – likely multifactorial and often results in a reduction in exercise capacity in early to late adolescence; contributing factors include the pulmonary complications listed above, anaemia and myocardial dysfunction
• Pulmonary fibrosis – occasionally seen in people with recurrent acute chest syndrome episodes