How Does Acute Chest Syndrome in Sickle Cell Disease Impact Lung Function?

Pulmonary function impairment was more frequent and inflammatory markers were elevated in pediatric patients with sickle cell disease (SCD) who experienced acute chest syndrome (ACS) versus those who did not experience ACS, according to an analysis of patient data from a previous randomized controlled trial, published in PLoS One.

The study, led by Aliva De, MD, of the Columbia University Irving Medical Center in New York, found a relationship between ACS and inflammation driven by interferon-inducible protein 10 (IP-10) and interleukin (IL)-6. “These findings suggest airway inflammation is present in children with SCD and ACS, which could be contributing to impaired pulmonary function,” Dr. De and colleagues wrote.

Researchers reviewed serum samples and pulmonary function test (PFT) data from 55 patients who had participated in a two-year clinical trial on high-dose and standard-dose vitamin D3 for the prevention of respiratory complications.

Compared with children with SCD without ACS, children with ACS had lower total lung capacity (TLC) at baseline and at year two, and had significant declines in forced expiratory volume in one second (FEV1; P=.015) and mid-maximal expiratory flow rate (P=0.39) over the study period. Children with ACS also had higher IL-5 and IL-13 serum cytokines at baseline and year two versus children without ACS.

Investigators noted that IP-10 and IL-6 were negatively correlated with PFT values. Based on multivariable regression models, age was significantly associated with FEV1 (P=.47) and FEV1 to forced vital capacity (FVC) ratios (P=.006). Additionally, males had lower FEV1/FVC ratios (P=.035) and higher TLC. Asthma was associated with FEV1 (P=.017) and FVC (P=.022), and history of ACS was significantly associated with TLC (P=.027).

Overall, “our present findings strengthen the association of ACS with lung function deficits and indicate that inflammatory mediators may be responsible,” Dr. De and colleagues wrote, concluding that, “with more insight into the underlying mechanisms of ACS in SCD leading to pulmonary injury, future therapeutic targets can be directed toward more specific disease mechanisms.”

Reference

De A, Williams S, Yao Y, et al. Acute chest syndrome, airway inflammation and lung function in sickle cell disease. PLoS One. 2023;18(3):e0283349. 2023. doi:10.1371/journal.pone.0283349