BAL neutrophilia in azithromycin-treated lung transplant recipients: Clinical significance

Vandermeulen, Elly; Verleden, Stijn E.; Ruttens, David; Moelants, Eva; Mortier, Anneleen; Somers, Jana; Bellon, Hannelore; Piloni, Davide; Dupont, Lieven; Raemdonck, Dirk Van; Proost, Paul; Schols, Dominique; Vos, Robin; Verleden, Geert M.; Vanaudenaerde, Bart M.

doi:10.1016/j.trim.2015.07.001

Cited by 17 publications

(29 citation statements)

References 23 publications

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“…One explanation of the persistently increased neutrophilia could be the presence of microorganisms, which are considered to be major risk factors for CLAD. Indeed, patients with high BAL‐neutrophilia under azithromycin showed higher abundance of Pseudomonas aeruginosa in BAL fluid . Several studies have already demonstrated a link between bacterial infections/colonization and an increased risk of the development of CLAD after lung transplantation .…”

Section: Discussionmentioning

confidence: 99%

“…However, neutrophilia may (re)develop in some patients despite azithromycin therapy for an unknown reason. As these patients suffer from a worse survival, neutrophils seem to be carrying an important prognostic role and might be involved in the pathophysiological mechanism . It is well known that activated neutrophils have the potential to cause damage to lung tissue due to their ability to generate reactive oxygen species and to release toxic proteases.…”

Section: Discussionmentioning

confidence: 99%

“…Twenty‐six percentage of our lung transplant recipients developed elevated (≥ 15%) BAL neutrophilia despite azithromycin treatment and these patients showed an inferior survival compared with patients without elevated BAL‐neutrophilia under azithromycin treatment . Up to now, no specific treatment is available and consequently survival remains poor after onset of azithromycin‐resistant neutrophilia (<3 years).…”

Section: Introductionmentioning

confidence: 94%

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Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cellsin vitro: assessing mechanisms and possible treatment options

et al. 2017

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Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK , Iκβ) and targets known to be involved in tumor formation (PI3K, Akt) were investigated. Finally, different treatment options were tested for their potential inhibitory effect. IL-1α induced IL-8 in bronchial epithelial cells, which was dose-dependently inhibited by dexamethasone but not by azithromycin. IL-1α induced p38 and Akt phosphorylation, but activation of these MAPK was not inhibited by dexamethasone. JNK, ERK , Iκβ and PI3K were not activated. None of the tested drugs reduced the IL-1α induced IL-8 production. We established an in vitro model wherein steroids inhibit the IL-1α-induced IL-8 production, while azithromycin was ineffective. Despite using this simple in vitro model, we could not identify a new treatment option for azithromycin-resistant airway neutrophilia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cellsin vitro: assessing mechanisms and possible treatment options

et al. 2017

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“…On the other hand, some patients do not respond to azithromycin therapy, with persistent shortness of breath and BAL neutrophilia. This azithromycin resistant neutrophilia compromises survival and is a risk factor for later CLAD [62].…”

Section: Acute Lung Allograft Dysfunctionmentioning

confidence: 99%

Lung Transplantation and Precision Medicine

Beeckmans

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Herck

et al. 2020

Precision in Pulmonary, Critical Care, and Sleep Medicine

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“…These patients usually present with a colonized graft (mostly pseudomonas) and demonstrate inferior survival compared to patients without neutrophilia (38). Interestingly, IL-1α is increased in BAL of those patients indicating that these alarmins might play an important role in the pathophysiology of BOS (39).…”

Section: Treatmentmentioning

confidence: 99%

Chronic lung allograft dysfunction phenotypes and treatment

et al. 2017

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CT and obliterative bronchiolitis (OB) on histopathology, while RAS/rCLAD patients show a restrictive pulmonary function, persistent pleuro-parenchymal infiltrates on CT and pleuroparenchymal fibro-elastosis on biopsies. Importantly, the patients with RAS/rCLAD have a severely limited survival post diagnosis of 6-18 months compared to 3-5 years after BOS diagnosis. In this review, we will review historical evidence for this heterogeneity and we will highlight the clinical, radiological, histopathological characteristics of both phenotypes, as well as their risk factors. Treatment of CLAD remains troublesome, nevertheless, we will give an overview of different treatment strategies that have been tried with some success. Adequate phenotyping remains difficult but is clearly needed for both clinical and scientific purposes.

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BAL neutrophilia in azithromycin-treated lung transplant recipients: Clinical significance

Cited by 17 publications

References 23 publications

Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cellsin vitro: assessing mechanisms and possible treatment options

Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cellsin vitro: assessing mechanisms and possible treatment options

Lung Transplantation and Precision Medicine

Chronic lung allograft dysfunction phenotypes and treatment

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