Highlights from

ATS 2019

American Thoracic Society international conference

Dallas, USA 17-22 May 2019

Aspergillus and early cystic fibrosis lung disease: does it need to be treated?

Using the AREST CF cohort (collected between 2000-2018 in Australia), researchers found that Aspergillus species are the most commonly isolated pathogen in young children with airway infection in cystic fibrosis (CF), yet it is unclear whether treatment is necessary. In this prospective cohort study, initial 1-year follow-up data indicates that CF patients with Aspergillus species infections are associated with progression of structural lung disease (especially trapped air), respiratory symptoms, respiratory exacerbations, and lower airway neutrophilic inflammation [1]. This data suggests an unmet need to actively treat these infections in young children with CF.

Dr Oded Breuer (Perth Children’s Hospital, Australia) began his presentation by reviewing the recent literature from the AREST CF cohort that contradicted the standard assumption that airway infection in CF initiates with Staphylococcus aureus and Haemophilus influenzae, with later emergence of Pseudomonas aeruginosa. Aspergillus species are regarded as relatively infrequent, late occurring infections. However, in young children in the AREST CF cohort, Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy. The decrease in prevalence of P. aeruginosa and S. aureus since 2000, coinciding with more aggressive therapeutic approaches, has resulted in Aspergillus becoming the most commonly isolated pathogen in young children [2]. The purpose of the study presented was to evaluate the longitudinal associations between Aspergillus infections and current and future indicators of lung disease in preschool patients with CF with the purpose to determine whether Aspergillus infections are a confounder in severe lung disease or whether this is a pathogen that should be treated and eradicated.

Participants with a CF diagnosis (n=330), of which 35% (n=115) were Aspergillus-positive, prospectively underwent bronchoalveolar lavage (BAL) at 3-6 months, 1 year, and annually up to 6 years of age in this cohort. A total of 1,631 hospital visits were replete with a BAL sample for analysis (n=186 Aspergillus-positive; n=1,445 Aspergillus-negative). Patients with Aspergillus infections were more likely to be older (3.9 vs 2.9 years, P<0.001) and were more likely to have taken azithromycin in the 3 months prior to the BAL (11% vs 5.3%, P=0.030) or had received intravenous antibiotic treatment at least once in the year prior to BAL (35.1% vs 20.6%, P=0.002). All patients received thorough clinical assessment, thoracic CT (CF-CT score and/or PRAGMA score), and neutrophilic inflammation assays (IL-8 and neutrophil elastase measurements) at every routine follow up with BAL sampling.

The major outcome of the study was structural lung disease in patients who were ever infected with Aspergillus, as determined by CF-CT and PRAGMA scores, both the current status and longitudinal progression after 1 year and at the end of study. Minor outcomes were the need for intravenous antibiotic treatment, clinical findings, and the presence of lower airway inflammation (IL-8, neutrophil elastase).

Aspergillus was mainly associated with trapped air and mucus plugging (both P<0.001) at the start of study. One year after the infection, Aspergillus was the main pathogen associated with a progression compared with baseline CT. End of study results indicated that patients that had ever had Aspergillus or Pseudomonas infections had worse structural lung disease by 5 to 6 years of age. Pseudomonas infection was mostly associated with bronchiectasis, whereas Aspergillus infection was mostly associated with trapped air.

With regard to the minor outcomes, Aspergillus infection had a significant effect on the risk for intravenous antibiotic therapy within a year of infection (P=0.013), and recurrent respiratory symptoms (P=0.007), compared with CF patients that were Aspergillus-negative (but possibly infected by other pathogen).

In summary, Aspergillus species infections are associated with progression of structural lung disease (especially trapped air), respiratory symptoms, respiratory exacerbations, and lower airway neutrophilic inflammation (although this was a hallmark for all 4 pathogens tested). The results suggest a detrimental role for Aspergillus infections on CF airways, and underscores the need to evaluate the safety and benefit of available treatments for aspergillus infections in children with CF.

  1. Breuer O, et al. Aspergillus and Early CF lung disease: guilty until proved innocent. A4003, ATS 2019, 17-22 May, Dallas, Texas, USA.
  2. Breuer O, et al. Am J Respir Crit Care Med. 2019 Feb 27.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.