Geert Verleden

Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome

Bronchiolitis obliterans syndrome is the major constraint on the long-term survival after lung transplantation. Both neutrophils and interleukin (IL)-8, a potent neutrophil attractant, have been shown to play an important role in the pathophysiology of obliterative bronchiolitis. We investigated the potential role of human airway smooth muscle cells in obliterative bronchiolitis by studying their release of IL-8 after stimulation with IL-17, a novel T-cell-derived chemokine capable of attracting and activating neutrophils. We demonstrated a significant increase in IL-8 release, reaching a concentration of 86.6 ng/ml (SEM 1.9 ng/ml) with 100 ng/ml IL-17 (p < 0.01, n = 4), as compared with non-stimulated cells. This IL-17-mediated IL-8 release could not be inhibited by dexamethasone. We conclude that human airway smooth muscle cells may play an important pro-inflammatory role in neutrophilic inflammatory diseases such as chronic rejection after lung transplantation; furthermore, IL-17 may be the link between lymphocytes and neutrophils.

Azithromycin Reduces Gastroesophageal Reflux and Aspiration in Lung Transplant Recipients

Azithromycin (AZI) is a macrolide antibiotic that improves lung function in lung transplant recipients (LTx). Gastroesophageal reflux (GER) has been implicated in the pathogenesis of chronic rejection after LTx. Macrolide antibiotics may affect GER by modifying esophageal and gastric motility. The purpose of this study was to evaluate the effect of AZI on GER and gastric aspiration after LTx. Acid and weakly acidic GER was measured with 24-h pH-impedance monitoring in 47 LTx patients (12 patients “on” AZI). Gastric aspiration was assessed in a separate group of 30 LTx patients before and after AZI by measurements of pepsin and bile acid in bronchoalveolar lavage fluid (BALF). Patients “on” AZI had a significant lower total number of reflux events [41 (30–61) vs. 22.5 (7–37.5)], number of acid reflux events [24 (16–41) vs. 8 (4–18)], esophageal acid exposure [2.9% (0.7–7.3) vs. 0.2% (0.1–2.0)], bolus exposure [0.73% (0.5–1.4) vs. 0.21% (0.12–0.92)], and proximal extent of reflux [14 (9–24) vs. 5 (2–7)]. AZI reduced the concentration of bile acids in BALF without affecting levels of pepsin. LTx patients “on” AZI have less GER and bile acids aspiration. This effect might be due to enhanced esophageal motility and accelerated gastric emptying.

Bilateral lobar lung transplantation--the first two cases in Belgium

Abstract In the last twenty years lung transplantation has become an established treatment for end-stage lung failure refractory to medical management. Over this time, better short and long-term results have been achieved due to improvements in organ procurement, perfusion and preservation strategies, newer immunosuppressant regimes and better post-transplant care. The limiting factor for the number of lung transplantation procedures performed is the shortage of available donor organs. This results in longer waiting times for listed patients, with a substantially increased risk of dying prior to transplantation, especially in the paediatric population. Several surgical strategies have evolved to overcome the donor shortage, with lobar transplantation becoming a viable alternative. We describe our initial experience with two young patients with end-stage cystic fibrosis (CF) who required lung transplantation. Given their small size it was not possible to transplant an entire lung from an adult donor in each hemithorax. We describe lobar transplantation as a technique used to overcome this, in the first such operation in Belgium.

Macrolides for the Treatment and Prevention of BOS

Chronic lung allograft rejection or its clinical correlate, the bronchiolitis obliterans syndrome (BOS), characterized by a persistent decline in forced expiratory volume in 1 s (FEV1) from an established baseline, is the single most important cause of death in lung transplant recipients after the first postoperative year. BOS is thought to be the final common endpoint of various injuries to the pulmonary allograft, triggering different innate and adaptive immune responses. Most preventive and therapeutic strategies for BOS have thus far been largely unsuccessful. However, the introduction of macrolide antibiotics, such as clarithromycin or particularly azithromycin (AZI), in the field of lung transplantation (LTx) as of 2003 made it clear that some patients with established BOS might in fact benefit from such therapy due to its various anti-inflammatory and immunomodulatory properties, as summarized in this chapter. Particularly in patients with an increased bronchoalveolar lavage (BAL) neutrophilia, AZI treatment could result in an increase in FEV1 of at least 10 %. More recently, it has become clear that prophylactic therapy with AZI actually may prevent BOS and improve FEV1 after LTx. However, one should always be aware of possible adverse effects related to AZI when implementing this drug as prophylactic or long-term treatment. Even so, AZI therapy after LTx can generally be considered as safe.