The Challenge of Obtaining Qualitative Bacterial Cultures in Non-expectorating Cystic Fibrosis Patients

Study Overview
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Brief Summary
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Accurate identification of lower respiratory tract pathogens is standard of care in the management of CF patients and it is therefore recommended to perform regular bacterial cultures, at least once a year, but some even recommend monthly cultures. This can be done through different methods, of which sputum and bronchoalveolar lavage (BAL) are the gold standard. However, BAL is an invasive method, not designated to repeat monthly. Therefore, the diagnosis of lower respiratory tract infections can be challenging in the non-expectorating CF patient. Other methods, such as induced sputum (IS), cough swabs and nasal swabs, have been developed to obtain bacterial cultures in these patients. Studies have investigated the reliability of these different sampling methods, however, with controversial conclusions.

Detailed Description
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I. Protocol design: The current protocol is designed to compare: Group 1: nasal swab, cough swab and spontaneous expectorated sputum in expectorating CF patients Group 2: nasal swab, cough swab and induced sputum in non-expectorating CF patients Group 3: nasal swab, cough swab, induced sputum and BAL in both expectorating and non-expectorating CF patients requiring clinically indicated bronchoscopy II. Flow chart: Nasal swab obtained by the physiotherapyst (PT) Patient rinses his mouth with water, followed by autogenic drainage Cough swab obtained by the PT Obtainment of 3rd (4th) sample: Group 1: Sputum sample voluntary expectorated by the patient Group 2 and 3: Induced sputum sample --> voluntary coughed up and expectorated by the patient after inhalation of 4ml of HS OR Group 3: BAL -->obtained by the pulmonologist during bronchoscopy Filling out questionnaire on acceptability of the different sampling methods by patients >6 years of age (not in Group 3) III. Analysis of the samples: (Induced) Sputum samples, cough and nasal swabs are aseptically collected in the appropriate disposable and are immediately sent to the Laboratory for Microbiology and Infection Control of the Universitair Ziekenhuis Brussel, where analyses are carried out within 24h post-sampling. These analyses include: Culture and identification of respiratory pathogens on selective and non-selective media Each type of colony will be identified by MALDI-TOF mass spectrometry, completed by other identification tests if needed When appropriate, susceptibility tests will be performed on the isolated bacteria IV. Statistical analysis: Determination of sensitivity, specificity, positive predicted value, negative predicted value of the different sampling methods Preference for one method over another: crosstabs, Chi-square test Pain experienced with any method (Yes/No): Student's t-test VAS-scale pain per method: ANOVA

Official Title
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The Challenge of Obtaining Qualitative Bacterial Cultures in Non-expectorating Cystic Fibrosis Patients

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Procedure: Nasal swab
* Procedure: Cough swab
* Procedure: Spontaneous expectorated sputum
* Procedure: Induced sputum
* Procedure: Bronchoalveolar lavage
* Other: Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both expectorating and non-expectorating CF patients with confirmed diagnosis (sweat test / genotyping) All ages Attending the UZ Brussel CF Clinic Written informed consent from each participant and/or his parents or legal guardian Exclusion Criteria: CF patients who underwent lung transplantation Denial of participation to the study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Expectorating CF patients<br>(=able to expectorate sputum spontaneously) Nasal swab Cough swab Spontaneous expectorated sputum Questionnaire | Procedure: Nasal swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Cough swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Spontaneous expectorated sputum<br>* Will be obtained by the physiotherapist in: - Expectorating CF patients<br>Other: Questionnaire<br>* Completing questionnaire on acceptability of different sampling methods by patients >6 years of age<br>|
| Non-expectorating CF patients<br>(=unable to expectorate sputum spontaneously) Nasal swab Cough swab Induced sputum after inhalation of hypertonic saline (NaCl 6%) Questionnaire | Procedure: Nasal swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Cough swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Induced sputum<br>* Will be obtained by the physiotherapist in: Non-expectorating CF patients Bronchoscopy CF patients<br>Other: Questionnaire<br>* Completing questionnaire on acceptability of different sampling methods by patients >6 years of age<br>|
| Bronchoscopy CF patients<br>(=undergoing clinically indicated bronchoscopy) Nasal swab Cough swab Induced sputum after inhalation of hypertonic saline (NaCl 6%) Bronchoalveolar lavage (BAL) | Procedure: Nasal swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Cough swab<br>* Will be obtained by the physiotherapist in: Expectorating CF patients Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Induced sputum<br>* Will be obtained by the physiotherapist in: Non-expectorating CF patients Bronchoscopy CF patients<br>Procedure: Bronchoalveolar lavage<br>* Will be obtained by the pulmonologist in: - Bronchoscopy CF patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity, specificity, positive and negative predicted value | Sensitivity, specificity, positive and negative predicted value of different sampling methods | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preference of method | If no differences are observed between sampling methods, which method would be preferred by the patient? | Questionnaire: day of sampling, Analysis: 2 years | 
| Pain experienced with any method | Is there any pain experienced? If so, how much? --> VAS | Questionnaire: day of sampling, Analysis: 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory sampling