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 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.

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 A Prospective Study of Adherence and Virologic Failure in HIV-Infected Patients: Role of a Single Determination of Plasma Levels of Antiretroviral Medications

2007 ◽  
Vol 6 (4) ◽  
pp. 245-250 ◽  
Author(s):  
María J. Cuevas González ◽  
Luis Ortega Valín ◽  
María del Rosario Pérez-Simón ◽  
José Luis Mostaza Fernández ◽  
Manuel Alcoba Leza ◽  
...  
Keyword(s):  
Prospective Study ◽  
Plasma Levels ◽  
Virologic Failure ◽  
Antiretroviral Medications ◽  
Single Determination ◽  
A Prospective Study

Mycobacterial lung disease in cystic fibrosis: a prospective study

1997 ◽  
Vol 16 (4) ◽  
pp. 354-358 ◽  
Author(s):  
BRIGITTE FAUROUX ◽  
BERTRAND DELAISI ◽  
ANNICK CLÉMENT ◽  
CAROLE SAIZOU ◽  
DIDIER MOISSENET ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Prospective Study ◽  
Lung Disease ◽  
A Prospective Study

Neutrophils in cystic fibrosis

2016 ◽  
Vol 397 (6) ◽  
pp. 485-496 ◽  
Author(s):  
Julie Laval ◽  
Anjali Ralhan ◽  
Dominik Hartl
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Structural Damage ◽  
Fungal Pathogens ◽  
Therapeutic Potential ◽  
Inflammatory Cells ◽  
Current Evidence ◽  
Infection And Inflammation ◽  
Shed Light

Abstract Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease.

scholarly journals The CFTR and ENaC debate: how important is ENaC in CF lung disease?

2012 ◽  
Vol 302 (11) ◽  
pp. L1141-L1146 ◽  
Author(s):  
James F. Collawn ◽  
Ahmed Lazrak ◽  
Zsuzsa Bebok ◽  
Sadis Matalon
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Bacterial Infections ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Ongoing Debate ◽  
The Subject ◽  
Cystic Fibrosis Transmembrane ◽  
Epithelial Sodium Channel Enac

Cystic fibrosis (CF) is caused by the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) function and results in a respiratory phenotype that is characterized by dehydrated mucus and bacterial infections that affect CF patients throughout their lives. Much of the morbidity and mortality in CF results from a failure to clear bacteria from the lungs. What causes the defect in the bacterial clearance in the CF lung has been the subject of an ongoing debate. Here we discuss the arguments for and against the role of the epithelial sodium channel, ENaC, in the development of CF lung disease.

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