Multi-country estimate of different manifestations of aspergillosis in cystic fibrosis

Joanne Armstead, Julie Morris, David W Denning, Joanne Armstead, Julie Morris, David W Denning

Abstract

Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those >18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were >18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: Dr. Denning holds founder shares in F2G Ltd a University of Manchester spin-out company and has current grant support from the National Institute of Allergy and Infectious Diseases, National Institute of Health Research, the European Union and AstraZeneca. He acts as a consultant to Trinity group, T2 Biosystems, GSK, as well as other companies over the last 5 years including Pfizer, Schering Plough (now Merck), Astellas and Gilead. In the last 3 years, he has been paid for talks on behalf of Astellas, GSK, Gliead and Pfizer. Armstead and Morris have no conflicts to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. The percentage of individuals with…
Figure 1. The percentage of individuals with CF stratified in 5 year age categories for numerous countries.
Figure 2. Alternative models of the development…
Figure 2. Alternative models of the development of ABPA, Aspergillus sensitisation or Aspergillus bronchitis.
Figure 3. Boxplot to show the difference…
Figure 3. Boxplot to show the difference in ages between the different diagnostic groups of aspergillosis.

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