Persistent Aspergillus linked to exacerbation risk in bronchiectasis

Key takeaways:

• Persistent Aspergillus was linked to shorter time to an exacerbation and a faster yearly rate of decline in percent predicted FEV₁.
• It also raised the risk for future exacerbations.

HONOLULU — Patients with non-cystic fibrosis bronchiectasis and persistent Aspergillus fumigatus faced a heightened risk for exacerbations, according to research presented at the CHEST Annual Meeting.

“[Bronchiectasis] is considered the third most prevalent airways disease,” Allison Michaud, MD, PhD, pulmonary fellow in the division of respiratory medicine at University of Calgary’s Cumming School of Medicine, said during her presentation. “Despite this, we don’t have a lot of research about non-cystic fibrosis bronchiectasis, and this is largely related to the fact that it’s a very heterogeneous group of patients.”

In a retrospective single center study, Michaud and colleague Christina S. Thornton, MD, PhD, FRCPC, assistant professor in the department of medicine at University of Calgary’s Cumming School of Medicine, assessed patients with non-cystic fibrosis bronchiectasis (NCFB) from the Calgary adult bronchiectasis clinic between 1981 and 2016 to determine if Aspergillus fumigatus — found through sputum samples — raised the risk for adverse outcomes.

Of the total cohort, 29 patients had persistent A. fumigatus (≥ 2 positive samples with carriage 6 months), whereas 102 had transient A. fumigatus (≥ 1 positive sample but did not meet persistent criteria).

Researchers also included 128 control patients with NCFB matched to those with persistent/transient A. fumigatus using age, birth cohort and sex.

To properly assess outcomes, researchers evaluated data 2 years before and after a patient contracted A. fumigatus, as well as 5 years after to account for lung transplants and mortality.

Between patients with transient A. fumigatus and control patients, researchers found comparable baseline characteristics and clinical outcomes; however, this was not true during the assessment of patients with persistent A. fumigatus and control patients.

Prior to accounting for confounding variables, these two sets of patients had differences in mean age (persistent, 68.5 years vs. control, 55.7 years; P < .001), BMI (20.2 kg/m² vs. 22.4 kg/m²; P = .008), percent-predicted FEV₁ (52.4% vs. 67.3%; P < .001) and a history of Pseudomonas aeruginosa (14% vs. 50%; P < .001).

Researchers also observed that significantly more patients with persistent A. fumigatus vs. controls had diabetes (31% vs. 15%; P = .003), allergic bronchopulmonary aspergillosis (31% vs. 0%; P = .005), antibiotic courses in 48 months (22% vs. 7%; P = .008) and proton pump inhibitor use (34% vs. 13%; P = .002).

Two clinical outcomes also varied between those with persistent A. fumigatus and control patients: median time to pulmonary exacerbation (152 days vs. 225 days; adjusted HR = 2.24; 95% CI, 1.69-2.99) and rate of decline in yearly absolute percent-predicted FEV₁ (–2.51% vs. –1.31%; 95% CI, –4.89 to –0.12).

Notably, progression to lung transplant or death did not significantly differ among the two sets of patients, according to researchers.

Following adjustment for baseline age, sex, FEV₁, P. aeruginosa co-infection and antibiotic history, multivariate analysis demonstrated a significant elevated risk for future exacerbations among persistent patients (aHR = 2.24; 95% CI, 1.69-2.99).

Other significant findings from this analysis included an increased risk for future exacerbations with Pseudomonas colonization (HR = 3.6; 95% CI, 2.65-4.76), female sex (HR = 1.26; 95% CI, 1.05-1.5) and a higher number of pulmonary exacerbations in the prior year (HR = 1.83; 95% CI, 1.53-2.2), according to Michaud.

Further, compared with patients aged older than 65 years, researchers found that younger patients had a significant reduced risk for exacerbations (< 50 years, HR = 0.78; 95% CI, 0.62-0.99; 50 to < 65 years, HR = 0.81; 95% CI, 0.66-0.99).

“Like in CF, in this study we saw negative consequences that were associated with persistent Aspergillus isolation,” Michaud said. “The reason for this remains unclear. We have theories that ... patients who have chronic Aspergillus may have increased inflammation at baseline that leads to worse clinical outcomes.

“There was also an interesting association where if patients have less Pseudomonas colonization, they had Aspergillus and so there’s a possibility that they’ve been exposed to less suppressive antibiotics, and this might lead to worse clinical outcomes,” she added.

Michaud highlighted several limitations of this study, with most of her critiques centered around the design and size of the study because it was a single-center retrospective study with a small cohort of patients from a clinic specifically for patients with bronchiectasis.

“Our next steps are to complete data extraction from the remaining 150 patients who have attended the bronchiectasis clinic between our study dates,” Michaud said. “[Additionally,] we have up to 40 years of data so we’re hoping to prolong this out and see what happens over the years and then compare sputum microbiomes between these different populations.”