<i>Candida albicans</i> in cystic fibrosis: “Opening statements presented, let the trial begin”

Chotirmall, Sanjay H.

doi:10.1002/ppul.23315

Cited by 8 publications

(3 citation statements)

References 5 publications

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“…Defective glucagon secretion in cystic fibrosis may increase the risk of hypoglycemia, which is seen even in individuals without CFRD [ 22 ]. Other studies have reported normal glucagon response to mixed meals in cystic fibrosis [ 62 , 63 ]. The possibility of an intrinsic α -cell defect has been raised by an observation that treating mouse islets with CFTR inhibitors increases glucagon secretion, perhaps via alteration of the α -cell membrane potential [ 56 ].…”

Section: Updates On Cfrd Pathogenesismentioning

confidence: 94%

Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

Yoon

2017

Journal of the Endocrine Society

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Diabetes is a common and important complication of cystic fibrosis, an autosomal recessive genetic disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis–related diabetes (CFRD) is associated with profound detrimental effects on the disease course and mortality and is expected to increase in prevalence as the survival of patients with cystic fibrosis continues to improve. Despite progress in the functional characterization of CFTR molecular defects, the mechanistic basis of CFRD is not well understood, in part because of the relative inaccessibility of the pancreatic tissue and the limited availability of representative animal models. This review presents a concise overview of the current understanding of CFRD pathogenesis and provides a cutting-edge update on novel findings from human and animal studies. Potential contributions from paracrine mechanisms and β-cell compensatory mechanisms are highlighted, as well as functional β-cell and α-cell defects, incretin defects, exocrine pancreatic insufficiency, and loss of islet cell mass. State-of-the-art and emerging treatment options are explored, including advances in insulin administration, CFTR modulators, cell replacement, gene replacement, and gene editing therapies.

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Section: Updates On Cfrd Pathogenesismentioning

confidence: 94%

Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

Yoon

2017

Journal of the Endocrine Society

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“…can cause localized and systemic infections and induce oral and genital thrush, vascular access device–related infections, and posttransplantation complications. 80 The potential of Candida spp . to cause lung function declines implementing a significant impact was demonstrated in different studies in pwCF.…”

Section: Treatment Of Fungal Pulmonary Infectionsmentioning

confidence: 99%

Clinical Relevance of Fungi in Cystic Fibrosis

Schwarz¹

2023

Semin Respir Crit Care Med

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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.

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“…Microorganisms, such as P. aeruginosa, H. influenzae , and non-tuberculous mycobacteria (NTM), are all commonly isolated in airways with bronchiectasis [ 24 , 108 , 110 , 111 ]. Fungi, notably Aspergillus, are increasingly being recognized as potential pathogens in both cystic fibrosis (CF) and non-CF bronchiectasis with an association with airway inflammation and disease severity [ 5 , 6 , 8 , 112 , 113 , 114 , 115 , 116 ]. Impaired mucociliary clearance and mucus-congested airways present an ideal environment for fungal colonization and sporulation.…”

Section: The Pulmonary Mycobiome In Health Copd and Bronchiectasismentioning

confidence: 99%

Clinical Aspergillus Signatures in COPD and Bronchiectasis

Tiew

Thng

Chotirmall

2022

JoF

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Pulmonary mycoses remain a global threat, causing significant morbidity and mortality. Patients with airways disease, including COPD and bronchiectasis, are at increased risks of pulmonary mycoses and its associated complications. Frequent use of antibiotics and corticosteroids coupled with impaired host defenses predispose patients to fungal colonization and airway persistence, which are associated with negative clinical consequences. Notably, Aspergillus species remain the best-studied fungal pathogen and induce a broad spectrum of clinical manifestations in COPD and bronchiectasis ranging from colonization and sensitization to more invasive disease. Next-generation sequencing (NGS) has gained prominence in the field of respiratory infection, and in some cases is beginning to act as a viable alternative to traditional culture. NGS has revolutionized our understanding of airway microbiota and in particular fungi. In this context, it permits the identification of the previously unculturable, fungal composition, and dynamic change within microbial communities of the airway, including potential roles in chronic respiratory disease. Furthermore, inter-kingdom microbial interactions, including fungi, in conjunction with host immunity have recently been shown to have important clinical roles in COPD and bronchiectasis. In this review, we provide an overview of clinical Aspergillus signatures in COPD and bronchiectasis and cover the current advances in the understanding of the mycobiome in these disease states. The challenges and limitations of NGS will be addressed.

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Candida albicans in cystic fibrosis: “Opening statements presented, let the trial begin”

Cited by 8 publications

References 5 publications

Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

Clinical Relevance of Fungi in Cystic Fibrosis

Clinical Aspergillus Signatures in COPD and Bronchiectasis

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