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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Procedure: Nasal swab; Procedure: Cough swab; Procedure: Spontaneous expectorated sputum; Other: Questionnaire; Procedure: Induced sputum; Procedure: Bronchoalveolar lavage

Detailed Description

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:

1. Nasal swab obtained by the physiotherapyst (PT)
2. Patient rinses his mouth with water, followed by autogenic drainage
3. Cough swab obtained by the PT

4. 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
5. 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

• Study Type: Observational
• Enrollment (Actual): 175

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

CF patients

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Study Director: Anne Malfroot, MD, PhD, Universitair Ziekenhuis Brussel - Cystic Fibrosis Clinic

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (Estimate): February 16, 2015

Study Record Updates

• Last Update Posted (Estimate): October 4, 2016
• Last Update Submitted That Met QC Criteria: October 2, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: respiratory sampling
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Dimercaprol
• Other Study ID Numbers: B.U.N. 143201422976

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be analysed and shared as an original article, individual data will only be available upon motivated request