scholarly journals Fungal Infection and Inflammation in Cystic Fibrosis

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 618
Author(s):  
T. Spencer Poore ◽  
Gina Hong ◽  
Edith T. Zemanick
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Clinical Outcomes ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Lower Airway ◽  
Future Research ◽  
Isolation And Identification ◽  
Helper Cell Type

Fungi are frequently recovered from lower airway samples from people with cystic fibrosis (CF), yet the role of fungi in the progression of lung disease is debated. Recent studies suggest worsening clinical outcomes associated with airway fungal detection, although most studies to date are retrospective or observational. The presence of fungi can elicit a T helper cell type 2 (Th-2) mediated inflammatory reaction known as allergic bronchopulmonary aspergillosis (ABPA), particularly in those with a genetic atopic predisposition. In this review, we discuss the epidemiology of fungal infections in people with CF, risk factors associated with development of fungal infections, and microbiologic approaches for isolation and identification of fungi. We review the spectrum of fungal disease presentations, clinical outcomes after isolation of fungi from airway samples, and the importance of considering airway co-infections. Finally, we discuss the association between fungi and airway inflammation highlighting gaps in knowledge and future research questions that may further elucidate the role of fungus in lung disease progression.

scholarly journals Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease

2019 ◽  
Vol 58 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Deepa Patel ◽  
Sarah Popple ◽  
Alison Claydon ◽  
Deborah E Modha ◽  
Erol A Gaillard
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Plasma Levels ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Tablet Formulation ◽  
Full Blood Count ◽  
Systemic Corticosteroids ◽  
Liquid Preparation ◽  
A Prospective Study

Abstract There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3–17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels >1 mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.

scholarly journals Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 716
Author(s):  
Claudia Lattanzi ◽  
Giulia Messina ◽  
Valentina Fainardi ◽  
Maria Candida Tripodi ◽  
Giovanna Pisi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Diagnostic Criteria ◽  
Respiratory Infections ◽  
Fungal Infections ◽  
Early Recognition ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Clinical Manifestations ◽  
Diagnostic Tools ◽  
The Impact

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF.

scholarly journals Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 357
Author(s):  
Aidan K. Curran ◽  
David L. Hava
Keyword(s):  
Cystic Fibrosis ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Hyphal Growth ◽  
Allergic Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Th2 Immune Response ◽  
Difficulty Breathing ◽  
Oral Corticosteroids

Aspergillus spp. are spore forming molds; a subset of which are clinically relevant to humans and can cause significant morbidity and mortality. A. fumigatus causes chronic infection in patients with chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In patients with CF, A. fumigatus infection can lead to allergic disease, such as allergic bronchopulmonary aspergillosis (ABPA) which is associated with high rates of hospitalizations for acute exacerbations and lower lung function. ABPA results from TH2 immune response to Aspergillus antigens produced during hyphal growth, marked by high levels of IgE and eosinophil activation. Clinically, patients with ABPA experience difficulty breathing; exacerbations of disease and are at high risk for bronchiectasis and lung fibrosis. Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF.

scholarly journals The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis

Thorax ◽  
2017 ◽  
Vol 72 (12) ◽  
pp. 1104-1112 ◽  
Author(s):  
Katherine B Frayman ◽  
David S Armstrong ◽  
Rosemary Carzino ◽  
Thomas W Ferkol ◽  
Keith Grimwood ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Longitudinal Analysis ◽  
Cystic Fibrosis Lung ◽  
Lower Airway ◽  
Cystic Fibrosis Lung Disease

Role of omalizumab in the management of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

2015 ◽  
Vol 144 (4) ◽  
pp. 190-191
Author(s):  
Isabel Delgado Pecellín ◽  
Esther Quintana Gallego ◽  
Celeste Pedregal Solano ◽  
Carmen Calero Acuña
Keyword(s):  
Cystic Fibrosis ◽  
Allergic Bronchopulmonary Aspergillosis

Potential role of the cellular allergen stimulation test (CAST) in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

2007 ◽  
Vol 42 (4) ◽  
pp. 314-318 ◽  
Author(s):  
Stephanie Ringer ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Felix Zintl ◽  
Jochen Mainz
Keyword(s):  
Cystic Fibrosis ◽  
Potential Role ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Stimulation Test

scholarly journals 2045 The role of TGFβ in driving early cystic fibrosis lung disease

2018 ◽  
Vol 2 (S1) ◽  
pp. 33-33
Author(s):  
Elizabeth L. Kramer ◽  
William Hardie ◽  
Kristin Hudock ◽  
Cynthia Davidson ◽  
Alicia Ostmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Transforming Growth Factor ◽  
Genetic Modifier ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Patient Specific

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

scholarly journals Why Beliefs About Emotion Matter: An Emotion-Regulation Perspective

2018 ◽  
Vol 28 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Brett Q. Ford ◽  
James J. Gross
Keyword(s):  
Emotion Regulation ◽  
Clinical Outcomes ◽  
Underlying Mechanism ◽  
Future Research ◽  
Wide Range ◽  
The World ◽  
Emotion Beliefs

The world is complicated, and we hold a large number of beliefs about how it works. These beliefs are important because they shape how we interact with the world. One particularly impactful set of beliefs centers on emotion, and a small but growing literature has begun to document the links between emotion beliefs and a wide range of emotional, interpersonal, and clinical outcomes. Here, we review the literature that has begun to examine beliefs about emotion, focusing on two fundamental beliefs, namely whether emotions are good or bad and whether emotions are controllable or uncontrollable. We then consider one underlying mechanism that we think may link these emotion beliefs with downstream outcomes, namely emotion regulation. Finally, we highlight the role of beliefs about emotion across various psychological disciplines and outline several promising directions for future research.

scholarly journals Airway Inflammation and Host Responses in the Era of CFTR Modulators

2020 ◽  
Vol 21 (17) ◽  
pp. 6379
Author(s):  
Karen Keown ◽  
Ryan Brown ◽  
Declan F. Doherty ◽  
Claire Houston ◽  
Michael C. McKelvey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Lung Disease ◽  
Airway Inflammation ◽  
Host Responses ◽  
Current Evidence ◽  
Future Research ◽  
Clinical Endpoints ◽  
New Class ◽  
Cftr Modulators

The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research.

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