Clinical Relevance of Fungi in Cystic Fibrosis

Abstract

In cystic fibrosis, a new era has started with the approval and use of highly effective cystic fibrosis transport regulator (CFTR) modulator therapy. As pulmonary function is increasing and exacerbation rate significantly decreases, the current meaning of fungal pulmonary diseases is questioned. During the past couple of decades, several studies have been conducted regarding fungal colonization and infection of the airways in people with cystic fibrosis. Although Aspergillus fumigatus for filamentous fungi and Candida albicans for yeasts remain by far the most common fungal species in patients with cystic fibrosis, the pattern of fungal species associated with cystic fibrosis has considerably diversified recently. Fungi such as Scedosporium apiospermum or Exophiala dermatitidis are recognized as pathogenic in cystic fibrosis and therefore need attention in clinical settings. In this article, current definitions are stated. Important diagnostic steps are described, and their usefulness discussed. Furthermore, clinical treatment strategies and recommendations are named and evaluated. In cystic fibrosis, fungal entities can be divided into different subgroups. Besides colonization, allergic bronchopulmonary aspergillosis, bronchitis, sensitization, pneumonia, and aspergilloma can occur as a fungal disease entity. For allergic bronchopulmonary aspergillosis, bronchitis, pneumonia, and aspergilloma, clear indications for therapy exist but this is not the case for sensitization or colonization. Different pulmonary fungal disease entities in people with cystic fibrosis will continue to occur also in an era of highly effective CFTR modulator therapy. Whether the percentage will decrease or not will be the task of future evaluations in studies and registry analysis. Using the established definition for different categories of fungal diseases is recommended and should be taken into account if patients are deteriorating without responding to antibiotic treatment. Drug–drug interactions, in particular when using azoles, should be recognized and therapies need to be adjusted accordingly.

Aspergillus and the Lung

“…74 Up to date, it is not yet clear whether or not the introduction of CFTR modulators reduces the burden of fungal lung disease in CF. 75,76 Aspergillus Bronchitis A. fumigatus is the most prevalent colonizing fungus in CF respiratory samples, and Aspergillus colonization may cause acute or chronic Aspergillus bronchitis in pwCF and bronchiectasis. 77 Chronically affected patients present with recurrent, frequently relapsing acute bronchitis.…”

“…74 Up to date, it is not yet clear whether or not the introduction of CFTR modulators reduces the burden of fungal lung disease in CF. 75 76…”

Pulmonary Aspergillosis in People with Cystic Fibrosis

“…Further studies with a prospective and interventional design could add more clarity to the field, focusing on the treatment aspect (when, how, and whom to treat). 3,10,59,65 Registry data show a decrease in bacteria but whether this is a true number and also true for fungi or if it is linked to the low amount of respiratory sputum is still not known.…”

“…1 2 After many years of observations, it is now well known that the chronic presence of fungal pathogens is associated with clinical and functional deterioration and morbidity, including pulmonary exacerbations requiring hospitalizations. 3 4 In addition, this fungal colonization of the airways is a significant risk factor for severe and often fatal infections in the post–lung transplant population. In the new era of highly effective CFTR modulator therapy, the role of pulmonary exacerbations or infections must be discussed in a new setting of clinically stabilized patients with increasing pulmonary function and a significantly reduced exacerbation rate.…”

The Spectrum of Pulmonary Aspergillosis

“…infection and disease in people living with cystic fibrosis, providing a window into the complexities and particularities of this specific population. 11 The contributions in this issue cover a wide array of topics, carefully elaborated by internationally recognized clinicians and scientists, each shedding light on a different aspect of pulmonary aspergillosis. We would like to extend our heartfelt gratitude to all the authors who have contributed their expertise, insights, and time to make this issue a treasure trove of evidence, clinical wisdom, and innovative insights into the management of pulmonary aspergillosis.…”