Would it have happened without Christmas? Thoracic emphysema and allergic bronchopulmonary aspergillosis in a juvenile cystic fibrosis patient with the G551D mutation receiving ivacaftor

Mainz, Jochen G.; Erdmann, Nina; Duckstein, Franziska; Zagoya, Carlos

doi:10.1183/23120541.00758-2020

Cited by 3 publications

(2 citation statements)

References 15 publications

(21 reference statements)

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“…In younger children carrying a G551D gating mutation, ivacaftor was shown to improve residual exocrine pancreatic function, as seen by weight gain and increased pancreatic elastase in stool (Rosenfeld et al, 2018). Some patients have even become pancreatic sufficient with ivacaftor therapy (Mainz et al, 2018;Rosenfeld et al, 2018;Mainz J. G et al, 2021). Such marked effects are not expected in pwCF carrying two severe non-gating mutations, such as F508del, owing to their extent of pancreatic destruction present in early life.…”

Section: Discussionmentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

et al. 2022

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Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score.Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations.Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined (“pain” 16.3 ± 1.6→10.2 ± 2.3, “GERD” 15.8 ± 1.8→8.2 ± 1.9, “disorders of bowel movement” 20.9 ± 1.5→16.0 ± 1.7, “disorders of appetite” 7.9 ± 1.1→2.6 ± 1.1 and “quality of life impairment” 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants’ symptoms mostly still did not reach the reference levels of HCs.Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI.

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Section: Discussionmentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

et al. 2022

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“…CFTR modulators in vitro have been shown to reduce radical oxygen species production by phagocytes induced by A. fumigatus , in both CF and control cells [ 73 ]. A case report signalled the occurrence of ABPA in a 13-year-old boy, despite treatment with ivacaftor [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review

et al. 2022

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BackgroundAspergillus fumigatus is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF.ObjectiveTo systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF.MethodsA systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932).ResultsA total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA.ConclusionScientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.

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Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators

Chatterjee,

Moss,

Omar

et al. 2024

JoF

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Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus (Af), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

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Would it have happened without Christmas? Thoracic emphysema and allergic bronchopulmonary aspergillosis in a juvenile cystic fibrosis patient with the G551D mutation receiving ivacaftor

Abstract: Potent CFTR-modulators improve CF manifestations far beyond expectations including reduction of risks for typical CF complications. Nevertheless, to our knowledge this is the first report on a patient who developed life-threatening ABPA and emphysema after overwhelming improvements.

Cited by 3 publications

References 15 publications

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review

Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators

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