Pseudomonas aeruginosaeradication therapy and risk of acquiringAspergillusin young children with cystic fibrosis

Abstract

BackgroundWhile Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.AimTo determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.MethodsCross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.ResultsCross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32–3.79) years and 3.69 (1.68–4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.ConclusionIn young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

The presence of Aspergillus fumigatus is associated with worse respiratory quality of life in cystic fibrosis

“…The presence of Af has been postulated to be a marker of disease severity and antibiotic exposure in CF; however, clinical markers of more advanced CF, such as Pa colonization, BMI, and FEV 1 percent predicted did not differ between the Af -positive and Af -negative groups. Unlike previous studies [14][15][16][17], chronic inhaled and oral antibiotics were not associated with the presence of Af . Whereas, subjects using inhaled corticosteroid use were more likely to recover Af in sputum; a relationship that has been previously reported [ 14 , 18 , 19 ].…”

An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway samples

“…Whilst it seems plausible that the presence of anti-fungal compound in the sputum of a chronic Pa patient may impact on these results, our within-patient analyses, in particular the significant dose relationships with Pa density, would argue against this and suggest a mechanism related to the bacterium itself. Other studies have reported an increase in Af prevalence with nebulised Pa eradication treatment [35] and chronic suppressive therapy [36][37][38][39] which would be complimentary to this data, suggesting that a reduction in Pa prevalence or density may lead to an increase in Af recovery on culture.…”

Lung Microbiome in Cystic Fibrosis

“…Another important aspect to note is the untargeted action that antibiotics can have on non-pathogenic bacteria, applying additional pressure on the lung microbial community [34]. Furthermore, it has been shown that antibiotic therapies used to eradicate P. aeruginosa can make the conditions favorable for acquiring Aspergillus in young CF subjects [35], causing a further imbalance in microbiome composition.…”