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

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.

Study Overview

• Status: Unknown
• Conditions: Paranasal Sinus Diseases; Cystic Fibrosis; Lungtransplantation
• Intervention / Treatment: Other: Bronchoalveolar and Nasal Lavage

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jens Gottlieb, Prof.; Phone Number: 4601 +49 511 532; Email: gottlieb.jens@mh-hannover.de
• Study Contact Backup: Name: Susanne Hoyer; Phone Number: 4601 +49 511 532; Email: hoyer.susanne@mh-hannover.de

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Department of Respiratory Medicine, Medizinische Hochschule Hannover

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult (age > 18 yrs)
• cystic fibrosis
• referral for lung transplantation or follow-up after lung transplantation receiving surgical treatment of sinus disease (sinus surgery) or onservative strategy of sinonasal inhalation of antibiotics
• for patients after lung transplantation: needing a previously scheduled flexible bronchoscopy via the nasal route on the date of baseline visit

Exclusion Criteria:

• no informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cystic fibrosis airway colonization; Flexible bronchoscopy via the nasal route on the date of baseline visit, nasal lavage at baseline and after 6 month	Other: Bronchoalveolar and Nasal Lavage; A previously scheduled flexible bronchoscopy via the nasal route on the date of baseline visit combined with a nasal lavage and another nasal lavage after 6 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
graft colonization after lung Transplantation (lower respiratory tract)	number of patients with positive microbiological testing of bronchoalveolar lavage	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of rhinosinusitic involvement	symptoms will be assessed with a specific questionnaire (SNOT22_GAV modified); Upper airway colonization with pathogens; Incidence of chronic lung allograft dysfunction, infections and hospitalizations	12 month
Upper airway colonization with pathogens	number of patients with positive microbiological testing of nasal lavage	12 month
Incidence of chronic lung allograft dysfunction, infections and hospitalizations	number of patients with new chronic lung allograft dysfunction, infections and hospitalizations respectivley	12 month

Collaborators and Investigators

• Sponsor: Hannover Medical School

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): January 1, 2016
• Study Completion (Anticipated): April 1, 2016

Study Registration Dates

• First Submitted: October 27, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Estimate): October 29, 2015
• Last Update Submitted That Met QC Criteria: October 28, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Nose Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Paranasal Sinus Diseases
• Other Study ID Numbers: LuTx-CF-colonization_1