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Immunopathogenesis
Published in Jonathan A. Bernstein, Mark L. Levy, Clinical Asthma, 2014
The second principal characteristic of asthmatic airway inflammation is the variable presence of structural changes in the airways, collectively termed remodeling.7 These include hypertrophy and hyperplasia of the airway smooth muscle cells, increased numbers of mucous goblet cells in the airway epithelium, deposition of extracellular matrix proteins (including collagen, fibronectin, and tenascin) beneath the epithelial basement membrane and in the submucosa, and neovascularization resulting in a proliferation of the vascular capillary beds within the submucosa. Some of these changes are not specific for asthma; for example, many chronic inflammatory processes involving the bronchial mucosa (asthma, COPD, bronchiectasis) are associated with mucous hypertrophy. Smooth muscle hypertrophy, hyperplasia and extracellular matrix protein deposited within the mucosa of the airways appear to be more asthma specific. These features have attracted great interest because they have been postulated to contribute to the accelerated decline in lung function and the irreversibility of airway obstruction observed in some, but not all asthmatics. Again, there are interpretational problems with this hypothesis. As already mentioned, some of these changes, such as airway mucosal edema due to neovascularization and blockage because of excessive mucus production, might intuitively be surmised to contribute to variable airway obstruction, while the deposition of extracellular protein might cause irreversible changes in airway function. However, as yet there is little or no direct evidence that they actually do so. Currently, remodeling changes in the asthmatic bronchial mucosa are widely assumed to result from the release of mediators from infiltrating inflammatory cells. While it is true that certain cytokines such as transforming growth factor beta (TGF-β) produced by eosinophils can cause bronchial mucosal fibroblasts to secrete fibrotic proteins such as collagen, while others such as interleukin-25 (IL-25) produced by T lymphocytes and other cells can promote neovascularization,8 there are still many doubts about the cause and effect relationship between inflammation and remodeling largely because it is so difficult to characterize the natural progression of these two phenomena. Confusingly, of the few studies conducted in children, some have reported that severe asthma is associated with airway remodeling,9,10 whereas others11 suggest that remodeling changes predispose to, but predate clinical asthma. Such studies cast doubt on the tenet that remodeling is caused by inflammation and, in turn, contributes to asthma symptoms and physiology. In both children and adults, remodeling changes have been linked to asthma severity but less clearly to disease longevity,9,10,12 suggesting that they are not necessarily cumulative, and even possibly at least partially reversible over time.
Clinical management of severe, fulminant, and refractory Clostridioides difficile infection
Published in Expert Review of Anti-infective Therapy, 2020
In animal studies, cytokine interleukin-25 (IL-25) signaling has been associated with the upregulation of eosinophils and subsequent decreases in cellular exudate, inflammatory cells, and intestinal epithelial barrier disruption, thereby decreasing CDI severity through protecting host tissue [20]. To explore eosinophilia as a predictor for CDI severity, Kulaylat and colleagues retrospectively examined 2065 admissions for CDI [21]. They found that compared to patients with detectable serum eosinophil counts, patients with undetectable levels had higher odds of in-hospital mortality (OR 2.26), admission to a monitored care setting (OR 1.40), vasopressor use (OR 2.08), and emergency total colectomy (OR 2.56).
Intranasal trigeminal function in chronic rhinosinusitis: a review
Published in Expert Review of Clinical Immunology, 2023
Anna Kristina Hernandez, Thomas Hummel
In addition, there exists a subtype of CRS with increased eosinophilia and nasal polyps. Eosinophils can release granule proteins which are neurotoxic [73–75] and may damage olfactory [24] and possibly trigeminal neurons as well. However, it appears that the effects are not unidirectional as the lack of innervation (possibly including trigeminal), observed in the study by Deng et al., was proposed to generate a pro-inflammatory state that causes SCC proliferation and increased interleukin 25 (IL-25) production which further drives type-2 inflammation [69].
Phenotyping severe asthma: a rationale for biologic therapy
Published in Expert Review of Precision Medicine and Drug Development, 2020
Alessandro Vatrella, Angelantonio Maglio, Simona Pellegrino, Corrado Pelaia, Cristiana Stellato, Girolamo Pelaia, Carolina Vitale
The alarmins interleukin-25 (IL-25), interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) are cytokines produced by the airway epithelium that contribute to the development of Th2-mediated adaptive immune responses [8]. In particular, IL-25, IL-33 and TSLP are capable of inducing innate lymphoid cells of type 2 (ILC2) to produce type T2 cytokines such as IL-5, IL-9 and IL-13 [62–65]. For this reason, these alarmins have been identified as potential targets for biological therapy [66].