Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis

Lands, Larry C.; Stanojevic, Sanja

doi:10.1002/14651858.cd001505.pub4

Cited by 49 publications

(9 citation statements)

References 19 publications

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“…CF lung disease is still the main cause of morbidity and mortality in CF despite intensive treatment [ 14 ]. Indirect pharmacological management focuses on anti-inflammatory agents [ 65 , 66 ], antibiotics [ 67 ], and mucolytic agents [ 68 ]. Direct pharmacological management of CF disease intends to restore the functional expression of mutated CFTR at the plasma membrane by correcting its folding and gating defect [ 69 ].…”

Section: Strategies Of Cf Therapymentioning

confidence: 99%

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Stolarczyk

Scholte

2018

Mediators of Inflammation

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Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R). This activity can be enhanced by injury, toxins, and receptor-mediated external triggers. In addition to intracellular kinases, the extracellular glutathione-dependent redox potential controls ADAM17 shedding. Thus, the epithelial ADAM17/EGFR axis serves as a receptor of incoming luminal stress signals, relaying these to neighboring and underlying cells, which plays an important role in the resolution of lung injury and inflammation. We review evidence that congenital CFTR deficiency in CF and reduced CFTR activity in chronic COPD may cause enhanced ADAM17/EGFR signaling through a defect in glutathione secretion. In future studies, these complex interactions and the options for pharmaceutical interventions will be further investigated.

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Section: Strategies Of Cf Therapymentioning

confidence: 99%

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Stolarczyk

Scholte

2018

Mediators of Inflammation

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“…This compound can reduce the lung inflammatory response of CF people. In parallel, a phase II clinical study to test the effectiveness and safety of LAU-7b in CF patients is underway (Lands and Stanojevic, 2016). LAU-7b, also called, Fenretidine, work to increase docosahexaenoic acid (DHA) and consequently CER concentration.…”

Section: Alternative Strategiesmentioning

confidence: 99%

“…In low doses, some shreds of evidence indicate that Ibuprofen may cause inflammation ( Lands and Stanojevic, 2019 ). Nonetheless, these outcomes are still a subject of debate among scientists who suspect the inappropriate use of Ibuprofen for CF patients ( Lands and Stanojevic, 2016 ). The association of Ibuprofen with infections is more complicated in that it confers risk in some situations but benefits in others, therefore its usage might require close monitoring ( Varrassi et al., 2020 ).…”

Section: History Of “Classical” Anti-inflammatory Drugsmentioning

confidence: 99%

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

Mitri

Bardin

et al. 2020

Front. Pharmacol.

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Cystic fibrosis (CF) is the most common genetic disorder among Caucasians, estimated to affect more than 70,000 people in the world. Severe and persistent bronchial inflammation and chronic bacterial infection, along with airway mucus obstruction, are hallmarks of CF lung disease and participate in its progression. Anti-inflammatory therapies are, therefore, of particular interest for CF lung disease. Furthermore, a better understanding of the molecular mechanisms involved in airway infection and inflammation in CF has led to the development of new therapeutic approaches that are currently under evaluation by clinical trials. These new strategies dedicated to CF inflammation are designed to treat different dysregulated aspects such as oxidative stress, cytokine secretion, and the targeting of dysregulated pathways. In this review, we summarize the current understanding of the cellular and molecular mechanisms that contribute to abnormal lung inflammation in CF, as well as the new anti-inflammatory strategies proposed to CF patients by exploring novel molecular targets and novel drug approaches.

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“…Several anti-inflammatory strategies have been investigated in the last 20 years though few of them have been translated into clinical application (see Table 1). The use of anti-inflammatory treatment, by aerosol or orally, is limited by the undesired side effects such as intolerance to glucose, diabetes, growth impairment, cataracts, gastrointestinal toxicity [31,32]. Therefore, the need to develop innovative immunomodulatory therapies aside from the classic anti-inflammatory agents is compelling.…”

Section: Cystic Fibrosis Lung Inflammation and Current Therapiesmentioning

confidence: 99%

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

Caretti

Peli

Colombo

et al. 2019

Cells

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Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF.

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Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis

Cited by 49 publications

References 19 publications

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

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