Relevance between clinical status and exhaled molecules related to neutrophilic inflammation in pediatric cystic fibrosis

Kanık, Esra Toprak; Yılmaz, Özge; Ozdogru, Ece; Alper, Hüdaver; Ulman, Cevval; Kanık, Ali; Şimşek, Yurda; Yüksel, Hasan

doi:10.1088/1752-7163/ab670d

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Recently the exhaled breath condensate (EBC) test was investigated to establish whether there was a link between inflammatory markers in the EBC and clinical outcome. NE was the only inflammatory marker found to be raised in EBC; conversely, this did not correlate with clinical outcome in these patients [157]. As, it has been reported that NE directly targets the CFTR interfering with its functionality [158], studies have aimed to inhibit NE and establish why previous NE inhibition studies have had mixed results [159,160].…”

Section: Neutrophilsmentioning

confidence: 98%

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Lara-Reyna

Holbrook

Jarosz-Griffiths

et al. 2020

Cell. Mol. Life Sci.

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Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infections and also in the regulation of tissue homeostasis. Innate immune cells are generally affected by CFTR mutations in patients with CF, leading to dysregulation of several cellular signalling pathways that are in continuous use by these cells to elicit a proper immune response. There is substantial evidence to show that airway epithelial cells, neutrophils, monocytes and macrophages all contribute to the pathogenesis of CF, underlying the importance of the CFTR in innate immune responses. The goal of this review is to put into context the important role of the CFTR in different innate immune cells and how CFTR dysfunction contributes to the pathogenesis of CF, highlighting several signalling pathways that may be dysregulated in cells with CFTR mutations.

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Section: Neutrophilsmentioning

confidence: 98%

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Lara-Reyna

Holbrook

Jarosz-Griffiths

et al. 2020

Cell. Mol. Life Sci.

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“…A further study has reported increased NE in the EBC of children with CF. However, nitric oxide, IL-17, IL-8, e-cadherin, NE, or leukotriene B4 levels in the EBC of CF children were not related to P. Aeruginosa infection, FEV 1 levels, or hospital admission in the last year ( 63 ). So far, sampling difficulties and variable results have failed to prove the usefulness of EBC in clinical practice.…”

Section: Other Biomarkersmentioning

confidence: 96%

Management of respiratory tract exacerbations in people with cystic fibrosis: Focus on imaging

Landini

Ciet²,

Janssens³

et al. 2023

Front. Pediatr.

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Respiratory tract exacerbations play a crucial role in progressive lung damage of people with cystic fibrosis, representing a major determinant in the loss of functional lung tissue, quality of life and patient survival. Detection and monitoring of respiratory tract exacerbations are challenging for clinicians, since under- and over-treatment convey several risks for the patient. Although various diagnostic and monitoring tools are available, their implementation is hampered by the current definition of respiratory tract exacerbation, which lacks objective “cut-offs” for clinical and lung function parameters. In particular, the latter shows a large variability, making the current 10% change in spirometry outcomes an unreliable threshold to detect exacerbation. Moreover, spirometry cannot be reliably performed in preschool children and new emerging tools, such as the forced oscillation technique, are still complementary and need more validation. Therefore, lung imaging is a key in providing respiratory tract exacerbation-related structural and functional information. However, imaging encompasses several diagnostic options, each with different advantages and limitations; for instance, conventional chest radiography, the most used radiological technique, may lack sensitivity and specificity in respiratory tract exacerbations diagnosis. Other methods, including computed tomography, positron emission tomography and magnetic resonance imaging, are limited by either radiation safety issues or the need for anesthesia in uncooperative patients. Finally, lung ultrasound has been proposed as a safe bedside option but it is highly operator-dependent and there is no strong evidence of its possible use during respiratory tract exacerbation. This review summarizes the clinical challenges of respiratory tract exacerbations in patients with cystic fibrosis with a special focus on imaging. Firstly, the definition of respiratory tract exacerbation is examined, while diagnostic and monitoring tools are briefly described to set the scene. This is followed by advantages and disadvantages of each imaging technique, concluding with a diagnostic imaging algorithm for disease monitoring during respiratory tract exacerbation in the cystic fibrosis patient.

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“…This leads to excessive infiltration of neutrophils, which are impaired in clearing the ongoing infection. Furthermore, CF-affected neutrophils have altered apoptosis ( Tirouvanziam et al., 2008 ) and increased neutrophil extracellular trap formation ( Gray et al., 2018 ), which is accompanied by high levels of neutrophil elastase in the airways of CF patients ( Garratt et al., 2015 ; Kanik et al., 2020 ). This vicious cycle of persistent infections and uncontrolled pro-inflammatory responses also causes severe oxidative stress through the release of reactive oxygen species (ROS) from neutrophils and CF epithelia, and the irreversible damage of lung tissues ( Bonfield et al., 1995 ; Chmiel and Davis, 2003 ; Davis, 2006 ; Cantin et al., 2015 ; Elborn, 2016 ; Turnbull et al., 2020 ).…”

Section: Cf Lung Disease and Inflammationmentioning

confidence: 99%

Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis

et al. 2020

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In individuals with cystic fibrosis (CF), lung hyper-inflammation starts early in life and is perpetuated by mucus obstruction and persistent bacterial infections. The continuous tissue damage and scarring caused by non-resolving inflammation leads to bronchiectasis and, ultimately, respiratory failure. Macrophages (MFs) are key regulators of immune response and host defense. We and others have shown that, in CF, MFs are hyper-inflammatory and exhibit reduced bactericidal activity. Thus, MFs contribute to the inability of CF lung tissues to control the inflammatory response or restore tissue homeostasis. The non-resolving hyper-inflammation in CF lungs is attributed to an impairment of several signaling pathways associated with resolution of the inflammatory response, including the heme oxygenase-1/carbon monoxide (HO-1/CO) pathway. HO-1 is an enzyme that degrades heme groups, leading to the production of potent antioxidant, anti-inflammatory, and bactericidal mediators, such as biliverdin, bilirubin, and CO. This pathway is fundamental to re-establishing cellular homeostasis in response to various insults, such as oxidative stress and infection. Monocytes/MFs rely on abundant induction of the HO-1/CO pathway for a controlled immune response and for potent bactericidal activity. Here, we discuss studies showing that blunted HO-1 activation in CFaffected cells contributes to hyper-inflammation and defective host defense against bacteria. We dissect potential cellular mechanisms that may lead to decreased HO-1 induction in CF cells. We review literature suggesting that induction of HO-1 may be beneficial for the treatment of CF lung disease. Finally, we discuss recent studies highlighting how endogenous HO-1 can be induced by administration of controlled doses of CO to reduce lung hyper-inflammation, oxidative stress, bacterial infection, and dysfunctional ion transport, which are all hallmarks of CF lung disease.

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Relevance between clinical status and exhaled molecules related to neutrophilic inflammation in pediatric cystic fibrosis

Cited by 3 publications

References 29 publications

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Management of respiratory tract exacerbations in people with cystic fibrosis: Focus on imaging

Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis

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