The best laid schemes of airway repair

Rawlins, Emma L.; Giangreco, Adam

doi:10.1183/09031936.00088014

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…In the lung, local stem cell pools have been identified in the conducting airways [110,111], among which the best characterised are airway basal cells with the potential for self-renewal and differentiation. Recent findings further suggest that differentiated tracheal club cells (Clara cells) are able to give rise to basal cells upon injury in a genetic model of basal progenitor cell ablation [112,113]. Their role in the development of CLDs needs to be further elucidated.…”

Section: Stem Cell Exhaustionmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases. @ERSpublications Hallmarks of ageing are selecting factors for the pathogenesis of COPD, lung cancer and IPF

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Section: Stem Cell Exhaustionmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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“…In a Phase II trial on asthmatic patients with nasal polyposis, asthma symptoms improved significantly ( P =0.012) along with a slight amelioration in clinical control as measured by ACQ. 51 In subsequent Phase III RCTs, significant improvements in FEV 1 and ACQ score were found, 52 particularly in the subgroup with nasal polyposis. 53 …”

Section: Anti-il-5 Mabs Beyond Mepolizumabmentioning

confidence: 99%

Clinical usefulness of mepolizumab in severe eosinophilic asthma

Menzella¹,

Lusuardi²,

Montanari³

et al. 2016

TCRM

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Asthma is a chronic inflammatory disorder of the airways with variable clinical severity from very mild and occasional symptoms to recurrent critical exacerbations, at risk of fatal or near-fatal outcome, in a small percentage of patients. Within the different inflammatory cascades involved in asthma, eosinophils play a central role in the pathogenesis and largely influence disease severity. Interleukin-5 (IL-5) is the main cytokine controlling eosinophil activity and proliferation at the site of inflammation. Mepolizumab was the first biological humanized anti-IL-5 monoclonal antibody tested in randomized clinical trials on eosinophilic asthma and other eosinophilic diseases. On the basis of several positive clinical efficacy data, it has recently been approved by the US Food and Drug Administration for the treatment of severe eosinophilic asthma. Unfortunately, high costs are at present a critical issue. Future studies will probably help in the correct selection of a potential “responder phenotype”, allowing the prescription of this promising therapy to appropriate patients and best define cost-effectiveness issues.

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“…This study showed significantly improved FEV 1 and ACQ score (treatment difference vs placebo: 115 and 160 mL, FEV 1 and 0.238 and 0.359 ACQ, respectively). 44 In another study performed in the United States, Castro et al evaluated reslizumab in subjects with elevated sputum eosinophils (>3%). The primary end point of this study was enhanced quality of life as suggested by improved ACQ scores.…”

Section: Reslizumab and Asthmamentioning

confidence: 99%

The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review

Patterson

Borish

Kennedy

2015

JAA

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Asthma is a heterogeneous syndrome that might be better described as a constellation of phenotypes or endotypes, each with distinct cellular and molecular mechanisms, rather than as a singular disease. One of these phenotypes is eosinophilic asthma. As the development of eosinophilic inflammation is categorically dependent on the biological activity of Interleukin (IL)-5, IL-5 antagonism became an obvious target for therapy in this phenotype. Early trials of monoclonal antibodies targeting the biological activity of IL-5, including reslizumab, mepolizumab, and benralizumab, were performed on asthmatics with no concern for evidence of eosinophilia. These trials were largely unsuccessful. However, during these trials, researchers recognized the need to quantify eosinophilia in asthma subjects in order to identify those asthmatics in whom these medications would be more likely to improve symptoms and lung function. Using biomarkers, such as sputum and blood eosinophilia, recent studies of these medications have shown improvements in blood and sputum eosinophilia, forced expiratory volume in 1 second, and quality of life assessments as well as reducing occurrences of exacerbations. Moving forward, better and less invasive biomarkers of eosinophilia are necessary to ensure that the correct patients are chosen to receive these medications to receive maximal benefit.

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The best laid schemes of airway repair

Cited by 10 publications

References 24 publications

Hallmarks of the ageing lung

Hallmarks of the ageing lung

Clinical usefulness of mepolizumab in severe eosinophilic asthma

The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review

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