Hemoptysis increases risk for serious outcomes in cystic fibrosis

Patients with cystic fibrosis who experience hemoptysis were found to be at higher risk for a lung transplant and death without a transplant, according to a study published in Annals of the American Thoracic Society.

“Over time, [people with cystic fibrosis] are at risk for increased respiratory symptoms and lung function decline, with many progressing to lung transplant or death without transplant,” Omar F. Bayomy, MD, internal medicine specialist from the University of Washington Medical Center, and colleagues wrote. “Furthering the understanding of possible associations between hemoptysis and lung transplant or death without transplant, particularly in patients with advanced cystic fibrosis (CF) lung disease, will contribute to an important gap in the literature and has the potential to impact clinical decision-making.”

In a retrospective cohort study, Bayomy and colleagues evaluated 18,347 patients with CF, aged at least 12 years, from the CF Foundation Patient Registry in 2016 to determine if having a hemoptysis complication raises the risk for a lung transplant or dying without a transplant over 3 years.

Patients from this dataset were grouped into one of three categories according to the severity of their hemoptysis: no hemoptysis; any hemoptysis (submassive and/or massive); or massive hemoptysis, which researchers identified as “acute airway bleeding [greater than or equal to] 240 ml in a 24-hour period or recurrent bleeding [greater than] 100 ml over several days.”

In order to find the relationship between the two factors, researchers used logistic regression and multivariable logistic regression that adjusted for age, sex, BMI, FEV₁, number of exacerbations, supplemental oxygen use, CF-related diabetes and Pseudomonas aeruginosa colonization status.

After accounting for patients lost in follow-up, the analysis included 813 patients with hemoptysis, including 103 (13%) with massive hemoptysis, and 16,589 patients without hemoptysis.

During the study period, 89 (11%) patients with hemoptysis received a lung transplant and 74 (9%) died without a transplant. In the group of patients with no hemoptysis, 567 (3%) received a lung transplant and 660 (4%) died without one.

Researchers also conducted a subgroup analysis among patients with an FEV₁ less than 40% predicted, or advanced lung disease, to assess their risk for the composite endpoint of a lung transplant or dying without one. This group included 191 patients with hemoptysis and 1,855 patients without hemoptysis. A greater proportion of those with vs. without hemoptysis had a lung transplant (36% vs. 22%) or died without one (24% vs. 17%).

According to researchers, patients with any instances of hemoptysis were at a higher risk for receiving a lung transplant or death without a transplant compared with the other group (OR = 1.3, 95% CI, 1.1-1.7).

Massive hemoptysis further increased the risk for a lung transplant and death without one among all patients (OR = 2.2, 95% CI, 1.2-3.8) and those with advanced lung disease (OR = 3.2, 95% CI, 1.3-8.2).

Patients with one episode of hemoptysis and no advanced lung disease did not appear to be at significant risk for lung transplantation or death without a transplant in a post-hoc analysis; however, researchers wrote that this finding does not entirely rule out an increased risk “given our 95% CIs of the ORs that are wide and nearing significance in this subgroup that may be underpowered.”

Researchers further found that removing FEV₁, adding Staphylococcus aureus, adjusting for CFTR modulator use and adding CF-related liver disease in sensitivity analysis did not significantly change the original associations.

However, this analysis did find higher chances of a lung transplant or dying without a transplant among patients categorized with having massive hemoptysis than patients categorized with having submassive hemoptysis in the total cohort (massive OR = 2.2, 95% CI, 1.2-3.8; submassive OR = 1.2, 95% CI, 0.9-1.5) and the advanced lung disease cohort (massive OR = 3.3, 95% CI, 1.3-8.8; submassive OR = 1.6, 95% CI, 1.1-2.4), according to researchers.

“Our results suggest that hemoptysis functions as a useful predictor of serious outcomes in people with cystic fibrosis with advanced lung disease and may be important to incorporate into risk prediction models and/or transplant decisions in CF,” Bayomy and colleagues wrote. “How highly effective [CF transmembrane conductance regulator] modulators impact hemoptysis and/or modify the effect of hemoptysis on serious outcomes will also be a key area for research as longer-term follow-up data become available in the future.”