ePS05.4 The impact of Aspergillus fumigatus on lung function and pulmonary exacerbation in children with cystic fibrosis

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

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Faculty Opinions recommendation of The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1165048.2474071 ◽

2010 ◽

Author(s):

Andrew Bush

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Aspergillus Fumigatus ◽

Chronic Infection

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Impact of Aspergillus fumigatus infection on lung function in children with cystic fibrosis

10.1183/13993003.congress-2021.pa3377 ◽

2021 ◽

Author(s):

Ludmila Balanetchi ◽

Rodica Selevestru ◽

Mariana Cotorobai ◽

Diana Rotaru-Cojocari ◽

Cristina Tomacinschi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Aspergillus Fumigatus

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Multivariate joint modeling to identify markers of growth and lung function decline that predict cystic fibrosis pulmonary exacerbation onset

BMC Pulmonary Medicine ◽

10.1186/s12890-020-1177-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

E. R. Andrinopoulou ◽

J. P. Clancy ◽

R. D. Szczesniak

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Joint Modeling ◽

Pulmonary Exacerbation ◽

Lung Function Decline ◽

Cystic Fibrosis Pulmonary Exacerbation

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P108 Chronic co-infection with Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis is associated with accelerated decline in lung function

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(20)30443-4 ◽

2020 ◽

Vol 19 ◽

pp. S86

Author(s):

K. Keown ◽

A. Reid ◽

J. McCaughan ◽

J.E. Moore ◽

C.C. Taggart ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Lung Function ◽

Aspergillus Fumigatus

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Lung function over the life course of paediatric and adult patients with cystic fibrosis from a large multi-centre registry

Scientific Reports ◽

10.1038/s41598-020-74502-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Arul Earnest ◽

Farhad Salimi ◽

Claire E. Wainwright ◽

Scott C. Bell ◽

Rasa Ruseckaite ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Pancreatic Insufficiency ◽

Forced Expiratory Volume ◽

Rate Of Change ◽

Data Registry ◽

Mortality Outcome ◽

The Impact

Abstract A key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Australian Cystic Fibrosis Data Registry (ACFDR). A linear mixed model was used to study FEV1pp as the endpoint. There were 3655 patients (52.4% male) included in our study. Restricted cubic splines were used to fit the non-linear relationship between age of visit and FEV1pp. The following predictors were found to be significant in the multivariate model: age of patient at visit, BMI z-score, age interaction with lung transplantation, insulin dependent diabetes, cirrhosis/portal hypertension, pancreatic insufficiency, Pseudomonas aeruginosa infection and baseline variability in FEV1pp. Those with P. aeruginosa infection had a lower mean difference in FEV1pp of 4.7 units, p < 0.001 compared to those who did not have the infection. Joint modelling with mortality outcome did not materially affect our findings. These models will prove useful for to study the impact of CFTR modulator therapies on rate of change of lung function among patients with CF.

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Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2017.06.002 ◽

2018 ◽

Vol 17 (1) ◽

pp. 83-88 ◽

Cited By ~ 17

Author(s):

Patrick A. Flume ◽

Claire E. Wainwright ◽

D. Elizabeth Tullis ◽

Sally Rodriguez ◽

Minoo Niknian ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Pulmonary Exacerbation

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Serum and Sputum Iron Trends Distinguigh Responders and Non-Responders to Treatment of Cystic Fibrosis Pulmonary Exacerbation

10.21203/rs.3.rs-52287/v1 ◽

2020 ◽

Author(s):

Alex H Gifford ◽

Deepika Polineni ◽

Jianghua He ◽

Jessica L D'Amico ◽

Dana B Dorman ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Iron Homeostasis ◽

Iron Concentration ◽

Symptom Burden ◽

Clinical Information ◽

Medical Decision ◽

Initial Increase ◽

Pulmonary Exacerbation ◽

Objective Evidence

Abstract Background: The cystic fibrosis (CF) community seeks to explain the heterogeneity of pulmonary exacerbation (PEX) treatment outcomes. Studies suggest that certain substances in serum and sputum offer objective evidence of PEX onset in people with CF (PwCF) and identify those at risk for inadequate treatment responses. However, it is clinically impractical to measure most of these substances, and a lack of correlative clinical information limits their utility as drivers of medical decision-making. Here, we questioned whether routinely available indices of iron homeostasis and systemic inflammation could identify PwCF with and without sustained symptom and lung function responses to PEX treatment. Methods: We prospectively evaluated health-related quality-of-life (HRQoL) and lung function and measured biochemical indices associated with iron homeostasis in serum and sputum in twenty adults during a PEX cycle. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores following initial improvement during PEX treatment. We used linear mixed models (LMMs) to explore whether treatment-related trends in lung function and hematologic and sputum parameters of interest differed between SRs and NSRs.Results: We identified ten SRs and ten NSRs. Subjects were adults with baseline lung function and symptom burden similar to other CF cohorts in the literature. SRs and NSRs were treated for similar durations. SRs had higher model-predicted trends in lung function than NSRs during treatment. Serum interleukin-6 (IL-6) and serum hepcidin-25 fell during treatment in SRs and NSRs. Trends in serum and sputum iron levels differed significantly between SRs and NSRs. Conclusions: In adults with CF treated for PEX, symptomatic non-response may be associated with lack of lung function improvement, initial increase but terminal decline in serum iron concentration, and initial decline but terminal increase in sputum iron concentration. Future work is needed to confirm the findings and understand possible mechanisms for these alterations in iron homeostasis during CF PEX.

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