In celebration of World Sickle Cell Day on June 19th The Lancet has published a series of specially commissioned articles on controversial topics in sickle cell. The first, written by Michael DeBaun, from Vanderbilt University, Nashville and Robert Strunk, from Washington University, St Louis, concentrated on the difficult and confusing association between asthma and sickle cell disease.
Asthma is common and familiar to most of us. Around 5.4 million individuals receive treatment for asthma in the UK, approximately 1 in every 12 adults and children. Asthma UK defines the condition as one that affects the airways, “the tubes that carry air in and out of your lungs. You could say that someone with asthma has sensitive airways that are inflamed and ready to react when they come into contact with something they don’t like”. Many “asthma triggers” are known including, infections such as colds and flu, cigarette smoke, stress and anxiety, exercise, cold air and allergies to pollen or pets. To quote Asthma UK again, “when a person with asthma comes into contact with something that irritates their sensitive airways it causes their body to react in three ways:
- the muscles around the walls of the airways tighten so that the airways become narrower
- the lining of the airways becomes inflamed and starts to swell
- sticky mucus or phlegm sometimes builds up, which can narrow the airways even more.
These reactions cause the airways to become narrower and irritated – making it difficult to breathe and leading to symptoms such as chest tightness, wheezing and coughing” – symptoms of a classic a asthma attack.
Because asthma is so common it is inevitable that some individuals with sickle cell disease will also have asthma, but the two diseases do not just occur together from time to time, they also interact in ways that have been difficult for doctors to disentangle and sort out.
The first problem is that it can be very difficult, particularly in young children, to distinguish between an episode of the acute chest syndrome and an acute asthma attack. Shortness of breath, wheezing and cough are symptoms common to both conditions and it is not uncommon for patients to be treated for both conditions at the same time.
Secondly, asthma and asthma-like symptoms are more common in children with sickle cell than in the general population. Wheezing, which is one of the classic symptom of asthma, is present in up to 70% of children with sickle cell and a formal diagnosis of asthma is made in 15-28% of sickle cell children.
Finally, if you have asthma it will make your sickle cell worse. Attacks of the acute chest syndrome occur more often, earlier in life and are associated with longer stays in hospital in the presence of asthma. Individuals with asthma will also have with more frequent painful crises. Recurrent attacks of the acute chest syndrome and frequent painful crises are associated with early mortality in sickle cell and, it is not surprising therefore, that a diagnosis of asthma also predicts earlier death.
How are we to understand the complex interaction between these two diseases? Professors DeBaun and Strunk suggest that an episode of the acute chest syndrome early in life sensitises the patient’s airways, either provoking full blown asthma or wheezing in susceptible individuals. A “second hit” with an asthma trigger such as a viral infection (young children have on average 6 a year), cigarette smoke or exposure to an allergen such as pollen, will provoke an asthma attack, but, in addition, by stimulating inflammation and reducing the flow of air and oxygen into the lungs, the episode of asthma can also evolve rapidly into the acute chest syndrome.
Whatever the details of the relationship between asthma and sickle cell disease, we know that individuals with both conditions are at increased risk. The authors emphasise how important it is for all sickle cell patients to be screened for asthma at each clinic visit, including the regular use of spirometry to measure their lung function. Once diagnosed the asthma needs to be treated effectively and treatment of the underlying sickle cell disease needs to be intensified, to prevent the two conditions interacting with each other in such a negative way.
The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia – Michael R DeBaun and Robert C Strunk. The Lancet (June 18th 2016), volume 387, pages 2545-2553.