Assessment of Cough Reflex in Lung Transplant Recipients

• ClinicalTrials.gov Identifier: NCT00584077
• Recruitment Status: Completed
• First Posted: January 2, 2008
• Results First Posted: September 25, 2015
• Last Update Posted: November 2, 2018
• Sponsor: The University of Texas Medical Branch, Galveston
• Information provided by (Responsible Party): The University of Texas Medical Branch, Galveston

Study Description

Brief Summary:

The purpose of this study is to evaluate the presence of cough reflex in the transplanted lung of patients who have had either a single or double lung transplant or heart-lung transplant at University of Texas Medical Branch. At the 1 year post transplant bronchoscopy, the presence of the cough reflex will be assessed by placing 3 to 5 ml of 5% dextrose and placement of the bronchial biopsy forceps on the airway mucosa. Three to four separate areas of the transplanted airways will be assessed. The cough reflex will be assessed by recording the surface electrical activity by placing external electrodes to monitor the movement of abdominal muscles during a cough. The data will be recorded and compared with recordings from coughs recorded using the surface electrical activity of a cough generated by non-transplant patients.

Condition or disease
Complication of Transplanted Lung

Detailed Description:

Bronchoscopy Stable, lung transplant recipients undergoing surveillance bronchoscopy will be enrolled. We will exclude subjects with new or persistent cough, hypoxemia, new radiographic infiltrates, or hemodynamic instability.

Before bronchoscopy, patients will receive diazepam while codeine and atropine will be withheld. Upper airway anesthesia was performed using cotton swabs soaked with 4 % lidocaine applied on the oropharyngeal mucosa and gradually placed posteriorly with the aid of curved foreceps to anesthetize the supraglottic region. A trained individual will perform topical upper airway anesthesia over 15 minutes and adequate anesthesia will be determined once subjects fail to cough during foreceps application to the supraglottic region. Conscious sedation will be administered using intravenous midazolam while vital signs are monitored. Once adequate sedation is achieved, the bronchoscope will be introduced through the mouth beyond the vocal chords to the main carina and slowly advanced to the airway anastomosis. Coughing that occurs with advancement of the bronchoscope from the chords to the anastomosis will be addressed by maintaining the bronchoscope in an immobile neutral position for 60-180 seconds until coughing stops and the cough provocation will be performed.

Cough provocation Airway irritants will be applied in the following sequence: 1) one cm distal to anastomosis, 2) one cm proximal to anastomosis and 3) at the main carina. Chemical irritation will consist of 3 mL aliquots of 5 % dextrose water (D5W) instilled through the bronchoscope channel on the bronchial mucosa (21). Aliquots of D5W will be administered at each site on three separate occasions with a 60 second interval between administrations. Mechanical irritation will involve placement of the biopsy foreceps on the bronchial mucosa at each site. The sequence of airway irritation sites will always begin with the distal anastomosis followed by the proximal anastomosis and main carina.

Airway lidocaine administration Patients demonstrating a cough reflex at the distal anastomotic site will be recorded. After measurements are obtained at all airway sites, the bronchoscope will be reintroduced to the distal anastomosis and 3 mL of 4 % lidocaine instilled on the bronchial mucosa. Sixty seconds later, mechanical and chemical irritation of the proximal and distal anastomosis will be performed as previously outlined.

Cough assessment Cough frequency will be determined by counting audible coughs and abdominal muscle contractions measured with a surface electromyograph (EMG) recorder. Surface electrodes placed on the skin, 2 cm below each costal margin along the midclavicular line will be connected to an EMG recorder (Biopac Systems Inc, Santa Barbara, CA) linked to a dedicated computer. Continuous EMG recordings will be obtained 15 seconds before administration of the airway irritant to ensure absence of cough before airway irritant administration (Figure 1). Twenty seconds or more of recording will be obtained after airway irritant application. Cough will be defined as abdominal muscle contraction and audible expiratory sound.

Study Design

• Study Type: Observational
• Actual Enrollment: 15 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Assessment of Cough Reflex in Lung Transplant Recipients
• Study Start Date: April 2000
• Actual Primary Completion Date: October 2006
• Actual Study Completion Date: October 2007

Groups and Cohorts

Group/Cohort
Stable lung transplant recipients; All enrolled subjects receive the same procedures; bronchoscopy with administration of mechanical and chemical irritants to the airway mucosa

Outcome Measures

Primary Outcome Measures :

1. Number of Coughs [ Time Frame: 15-20 minutes ]
   The number of coughs elicited by placement of biopsy forceps or instillation of dextrose solution on the airway mucosa. The presence of the cough reflex will be assessed with administration of mechanical (biopsy foreceps) and chemical (D5W) at the level of the main carina, proximal to airway anastomosis (native airway) and distal to the airway anastomosis (allograft airway).

Secondary Outcome Measures :

1. to Assess the Presence and Strength of the Cough Reflex in the Lower Airway for up to One Year [ Time Frame: 15-20 minutes ]

   Presence of cough as elicited by placement of biopsy forceps or instillation of dextrose solution on the airway mucosa. The presence of the cough reflex will be assessed with administration of mechanical (biopsy foreceps) and chemical (dextrose solution) at the level of the main carina, native lung airway and proximal and distal to the airway anastomosis. Lung transplant recipients underwent airway evaluations using the above protocel at 1.5 and 12 months after lung transplantation.

   after undergoing transplantation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Single or double lung or heart-lung transplant recipients

Criteria

Inclusion Criteria:

• Lung transplant recipient
• Hemodynamically stable
• Capable of undergoing bronchoscopy

Exclusion Criteria:

• Pneumonia
• Hypoxemia (PaO2 < 70)
• Hemodynamic instability
• Coagulopathy
• Thrombocytopenia

Contacts and Locations

Locations

United States, Texas

University of Texas Medical Branch

Galveston, Texas, United States, 77555

Sponsors and Collaborators

The University of Texas Medical Branch, Galveston

Investigators

• Principal Investigator: Alexander G Duarte, MD; University of Texas

More Information

Publications of Results:

Duarte AG, Terminella L, Smith JT, Myers AC, Campbell G, Lick S. Restoration of cough reflex in lung transplant recipients. Chest. 2008 Aug;134(2):310-316. doi: 10.1378/chest.07-2934. Epub 2008 Mar 13.

• Responsible Party: The University of Texas Medical Branch, Galveston
• ClinicalTrials.gov Identifier: NCT00584077
• Other Study ID Numbers: 00-132
• First Posted: January 2, 2008
• Results First Posted: September 25, 2015
• Last Update Posted: November 2, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No