A. Schoonis

A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation

Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV1) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS. A double-blind randomised controlled trial of azithromycin (n = 40) or placebo (n = 43), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005–2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV1, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV1 with open-label azithromycin. BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p = 0.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092–0.816; p = 0.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV1 (p = 0.028), and lower airway neutrophilia (p = 0.015) and systemic C-reactive protein levels (p = 0.050) over time. Open-label azithromycin for BOS improved FEV1 in 52.2% patients. No serious adverse events were noted. Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV1 and reduces BOS 2 yrs after LTx.

Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re‐evaluated the long‐term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention‐to‐treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD‐free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long‐term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long‐term CLAD prevalence and improves CLAD‐free survival, pulmonary function, and functional exercise capacity after LTx.

Exhaled carbon monoxide as a noninvasive marker of airway neutrophilia after lung transplantation

Background. Neutrophilic airway inflammation and associated oxidative stress contribute to airway injury and the development of bronchiolitis obliterans syndrome after lung transplantation (LTx). Exhaled carbon monoxide (eCO) reflects heme oxygenase-1 activity in response to oxidative stress. We investigated whether airway neutrophilia and eCO levels are associated in stable LTx recipients. Methods. In this cross-sectional pilot study, 45 stable LTx recipients were included. During routine follow-up at the outpatient clinic, pulmonary function testings together with eCO measurements before broncho-alveolar lavage (BAL) were performed. BAL cell differentials and interleukin (IL)-8 protein levels were assessed and correlated with eCO. Results. In the studied cohort, eCO levels were increased in patients with elevated (>3%) BAL neutrophilia compared with those with normal BAL neutrophilia (P=0.025). Furthermore, eCO levels significantly correlated with BAL neutrophilia and IL-8 levels in the cohort as a whole (r=0.50; P=0.0005 for total cells, r=0.43; P=0.003 for %cells and r=0.30; P=0.045 for IL-8). This was even more obvious in the LTx recipients with increased (>3%) BAL neutrophilia (r=0.70; P=0.0007 for total cells and r=0.80; P<0.0001 for %cells). For a cutoff of 4 ppm, sensitivity, specificity, positive and negative predictive value of eCO for detecting elevated BAL neutrophilia were 84.0%, 45.0%, 65.6%, and 69.2%, respectively (P=0.049). Conclusions. Elevated eCO levels in stable LTx recipients may reflect an increased BAL neutrophilia and could, therefore, be used as a noninvasive marker for airway inflammation after LTx.

Smoking resumption after lung transplantation: a sobering truth

To the Editors: About 40% of lung transplants (LTx) are performed for end-stage emphysema in former smokers 1. Patients are principally only enrolled on the waiting list after having quit smoking for at least 6 months 1. Some LTx recipients may resume smoking, which could complicate post-transplant outcome 2. Surprisingly, most LTx centres do not monitor smoking habits. We assessed all 267 LTx recipients currently in follow-up at our centre for smoking, after informed consent and approval by the local Ethical Review Board. Smoking behaviour was investigated by a standardised questionnaire, measurement of urinary cotinine (COT) and exhaled carbon monoxide (eCO) levels. The questionnaire addressed past and current smoking habits (regular or occasional active smoking and second-hand smoking, i.e. passive exposure via relatives or environmental exposure via social/work-related contacts) as well as the use of nicotine-replacement therapy (NRT). COT was assessed by gas chromatography and mass spectrometry (Thermo Scientific, Geel, Belgium) and eCO by using an electrochemical sensor (Bedfont Scientific, Kent, UK; detection limit 1 ppm), as previously described 3, 4. Statistical analyses were performed with Graphpad Prism 4.0 (San Diego, CA, USA). An unpaired t-test, Mann–Whitney U-test or Fishers exact test were used where appropriate and receiver–operating characteristic curve analysis was used for calculation of predictive values. LTx recipients (bilateral/single/heart–lung transplantation n = 190/59/18) were assessed at a median (interquartile range) of 3.4 (1.5–6.0) yrs after LTx. Prior to LTx, 166 (62%) out of 267 patients were former smokers and 101 (38%) out of 267 never-smokers. Former smokers reported smoking cessation at a median of 4.0 (1.5–10.0) …

Implementing a standardized, evidence-based education program using the patient's electronic file for lung transplant recipients.

Context Patient education is crucial to guarantee that transplant recipients are capable of adequate self-management. Until recently, our education program to prepare lung transplant patients for discharge lacked a systematic approach, meaning that it was unclear whether all key information had been provided and whether the patient understood the information. A lack of coordination among the multi-disciplinary team members also was apparent. Objectives (1) To map out a structured education program, outlining the content, process, and evaluation of education for patients before discharge after lung transplant; (2) to integrate this program into the patients electronic file and pilot test this new form of education tracking. Methods We used the conceptual framework of Lorig and colleagues, as well as the educational leaflets of the International Transplant Nurses Society, to generate the content of our education program. The interdisciplinary lung transplant team decided when and by whom each educational component should be provided, as well as the evaluation criteria. Next, information technology engineers integrated this educational program into the patients electronic file. Nurses subsequently tested the program, and their feedback was integrated in the next version of the program. Results Health care providers experienced a higher level of uniformity and transparency. After using the education program, most patients indicated that they felt confident to go home. Conclusion Our electronic educational platform is promising, yet further testing is necessary to evaluate whether patients indeed have sufficient knowledge and show adequate self-management skills in the long term after transplant.