Upper and Lower Airway Colonization in Cystic Fibrosis Patients After Lung Transplantation

Overview

A hot topic in lung transplantation is the treatment of persisting sinus disease/colonization in CF patients to prevent descending graft colonization and chronic allograft dysfunction. From 2012, the Hannover transplantation group has been using a conservative approach with topical nasal inhalation. It is now necessary to analyse the impact of the new approach on graft colonization, incidence of BOS, symptoms, QoL etc in comparison to a historical cohort. It is also important to establish which is the best among the different inhaled antibiotic regimens currently available.

These patients will undergo frequent individual centre based follow up care. At each follow up visit, patients will: * receive comprehensive clinical examination, history of intercurrent infections and sinus surgery * receive quantitative assessment, consisting in spirometry (performed according to ATS/ERS guidelines), arterial blood gas analysis, measurement of immunosuppressive drug levels and chest radiographs * receive questionnaires (quality of life (SNOT-20 GAV), side effects of sinus inhalation, symptom scores) * be asked to collect a sample of nasal lavage; a sample of BAL (obtained from routinely performed bronchoscopy) will also be collected. These specimens will be analysed for microbiological work up and evaluation of inflammatory markers. The principle of vibrating inhalation is implemented in novel nebulizers, with which sinonasal inhalation is performed by aerolized medication into one nostril, while the contralateral nostril is occluded and the soft palate elevated as recommended for nasal lavage. The medication is administered into both nostrils for 4-6 min each side during phases of arrest of breathing. Choice of antibiotics depends on resistance testing from microbiological results. Patients will be divided into different groups, on the basis of the inhaled antibiotic regimen being chosen: colistin vs. tobramycin. An alternate therapy with hypertonic saline may be applied to improve sinus clearance. All regimens will be administered with the same machine, i.e. PARI Sinus ™ nebulizer, which, unlike conventional aerosols, allows the deposition of drugs directly into the paranasal sinuses. The aims of this study are: * to assess sinus - and pulmonary colonization in cystic fibrosis (CF) lung transplant (LuTx) recipients (frequency of pathogen colonization; load; bacterial species) * to study association with clinical events (e.g. infections and development of bronchiolitis obliterans syndrome (BOS)) * to develop an optimal inhaled regimen (continuous inhalation/on-off regimen; single or combined antibiotics). * to compare cohorts receiving sinus surgery in a historical control to a cohort receiving our current conservative strategy (since 2012) of sinonasal vibrating inhalation of antibiotics, in terms of graft colonization, quality of life, overall survival, incidence of chronic lung allograft dysfunction * to compare inflammatory mediators in upper and lower airway lavages in regard to pathogen colonization, lung function and development of BOS