Abstract
BackgroundThe relationship between fungal culture (FC) positivity and airway inflammation in CF is largely unknown. Identifying the clinical significance of filamentous fungi in CF using both clinical parameters and biomarkers may change our antimicrobial therapeutic strategies.ObjectivesTo investigate the clinical characteristics and airway biomarker profile in relation to the detection of filamentous fungi in respiratory samples obtained from CF patients.MethodsA prospective cohort study over 24 months, including children and adults with CF. Participants provided sputum and/or bronchoalveolar lavage samples, which underwent processing for bacterial and fungal culture, leukocyte differential cell count and biomarker analysis for neutrophil elastase (NE), interleukin-8 (IL-8), galactomannan and tumor necrosis factor receptor type 2 (TNF-R2). We performed FC using neat sputum plugs, an approach shown to be more sensitive compared to routine laboratory testing.ResultsSixty-one patients provided 76 respiratory samples (72 sputum and 4 BAL). Median age was 17 years (range 6 months–59 years). FC positivity was noted in 49% of the cohort. FC positivity was greater during pulmonary exacerbation compared to the stable state (67 versus 50%). Participants aged 5–30 years had a lower FEV1 within the FC positive group. A significant association between FC positivity and non-tuberculosis mycobacterial (NTM) culture was observed on non-parametric testing (p = 0.022) and regression analysis (p = 0.007). Exposure to indoor mold was a predictor for FC positivity (p = 0.047). There was a trend towards increased lung clearance index (LCI), bronchiectasis and intravenous antibiotic use in the FC positive group. There was no significant difference in biomarkers between FC positive and negative patients.Conclusion Aspergillus. fumigatus is the commonest filamentous fungi cultured from CF airways. We found no difference in the airway biomarker profile between FC positive and negative patients. The role of galactomannan and TNFR2 as fungal specific biomarkers in CF remains uncertain. FC positivity is associated with a lower FEV1 in younger patients, a lower LCI, NTM positivity, bronchiectasis, and intravenous antibiotic exposure. Larger trials are needed to determine the role of galactomannan and TNF-R2 as potential fungal biomarkers in CF.
Highlights
Cystic fibrosis (CF) lung disease involves impaired mucociliary clearance leading to pulmonary inflammation, infection, and a more rapidly declining lung function
Twelve patients were excluded as no respiratory sample for fungal culture was obtained (Figure 1)
All 61 participants provided a sputum sample during the stable state, of whom 43 patients produced respiratory samples suitable for biomarker analysis
Summary
Cystic fibrosis (CF) lung disease involves impaired mucociliary clearance leading to pulmonary inflammation, infection, and a more rapidly declining lung function. Whilst the association between pathogenic bacteria and airway inflammation, infection and disease progression is well established (Hauser et al, 2011), less is known about the role of fungi in the CF airways and their impact on airway inflammation and lung disease progression. Allergic bronchopulmonary aspergillosis (ABPA) is a well-established complication in CF associated with sensitization to Aspergillus fumigatus (Thia and Balfour Lynn, 2009). In the absence of ABPA, it is not clear whether the detection of fungi in the CF airway in asymptomatic patients reflects simple colonization (innocent bystander effect) or infection contributing to increased airway inflammation (Liu et al, 2013; Chotirmall and McElvaney, 2014). A. fumigatus is the commonest filamentous fungus isolated from CF airways (Pihet et al, 2009; Sudfeld et al, 2009). Identifying the clinical significance of filamentous fungi in CF using both clinical parameters and biomarkers may change our antimicrobial therapeutic strategies
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