Severe CF flareups cause temporary pulmonary hypertension in 1 in 4 kids
New study finds age, inflammation tied to PH risk in children with CF
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About one-quarter of children with cystic fibrosis (CF) who are hospitalized for pulmonary exacerbations — an acute worsening of lung symptoms, often marked by increased cough and thicker or more mucus — will temporarily develop pulmonary hypertension (PH), a condition marked by high pressure in blood vessels that supply the lungs.
Those are the findings of a new study from Iran, which identified several factors, including older age, that raise the risk of temporary PH among youngsters with CF. Other factors associated with an increased risk of developing PH were a need for noninvasive ventilation support during hospitalization and elevated levels of inflammatory markers.
Importantly, the researchers noted that no child still had PH after recovering from the pulmonary exacerbation event.
“These findings suggest that transient PH during [pulmonary exacerbations] may reflect the reversible pulmonary vascular changes secondary to inflammation and hypoxia [low oxygen levels] rather than chronic pulmonary vascular remodeling,” the researchers wrote. Vascular remodeling refers to structural alterations to blood vessels, a key feature in PH.
However, the team called for more research into that risk.
The study, “Pulmonary hypertension in pediatric patients with cystic fibrosis during acute pulmonary exacerbations: prevalence and associated factors,” was published in the journal BMC Pulmonary Medicine.
CF is caused by mutations in the CFTR gene, which encodes a protein of the same name that normally helps cells regulate the flow of salt and water. These mutations result in the loss or dysfunction of CFTR protein, leading to the production of thick and sticky mucus in several organs, including the lungs.
CF patients can experience flare-ups that lead to hospitalization
People with CF may experience acute pulmonary exacerbations, or flare-ups marked by worsening respiratory symptoms and lung function. During an acute pulmonary exacerbation, airway infection and inflammation may contribute to structural remodeling and narrowing of blood vessels, which lead to PH.
Here, the researchers investigated the prevalence and factors associated with PH in kids with CF during hospitalization due to moderate to severe pulmonary exacerbations. The study enrolled 107 children, slightly more than half of them girls (57%), with a mean age of 9.
CFTR modulator therapies were unavailable to these children, according to the scientists. Instead, the participants were treated with inhaled hypertonic saline, Pulmozyme (dornase alfa), and tobramycin.
Three-quarters of the children had normal pulmonary arterial pressure (PAP), while 26 patients had high PAP (25 mmHg or higher). None of the children were found to have PH on follow-up examination after recovering from the acute pulmonary exacerbation.
Older kids were more likely to have temporary PH
Those with high PAP were significantly older — 14 versus 9 years of age — than the group with normal PAP. Those with elevated PAP also had higher levels of inflammatory markers, including C-reactive protein (CRP, 26.5 vs. 7 mg/dL) and erythrocyte sedimentation rate (ESR, 26 vs. 11 mm/hour).
The researchers found that all children with high PAP had major abnormalities as seen on a chest X-ray, compared with 81.5% of those with normal PAP. Also, noninvasive ventilation during the hospital stay was more frequently needed by children with elevated PAP (57.7% vs. 30.9%). However, neither parameters of lung function nor exercise capacity were significantly different between the two groups.
Among all children, the most common symptoms were cough (81%), sputum (60%), fever (44%), loss of appetite (32%), and feeling unwell (26%). Most children had sputum samples indicating infection (66%). A total of 20% were admitted to the intensive care unit.
Long-term studies are needed to determine if patients who experience [temporary] PH during [pulmonary exacerbations] face a higher risk of progressing to chronic PH in comparison to the general CF population.
Analyses indicated that the odds of having PH increased with older age, need for noninvasive ventilation, and higher levels of CRP and ESR. These associations were maintained after adjusting for the children’s age, sex, and lung function, as assessed by forced expiratory volume in 1 second (FEV1), which measures the amount of air forcefully exhaled in the first second after a deep breath.
Specifically, PH risk increased by nearly 18% with each additional year of age and was almost three times higher in children who required noninvasive ventilation. Additionally, CRP levels higher than 12 mg/dL increased the risk of PH by about 3.7 times, and ESR levels above 21 mmHg by 15%.
“Further studies are required to inform policy on monitoring strategies and resource allocation in the management of pediatric CF with [pulmonary exacerbations],” the researchers wrote. Also, “long-term studies are needed to determine if patients who experience PH during [pulmonary exacerbations] face a higher risk of progressing to chronic PH in comparison to the general CF population.”
