Sample Collections From the Airways of Asthmatic Patients

Asthma Sample Collection Protocol

Fiberoptic bronchoscopy is a procedure which involves passing a pencil-thin tube into the lung in order to collect fluid and cells from the airways. Fiberoptic bronchoscopy can collect cells from the walls of airways by gently brushing them (bronchial brushing). In addition, squirting small amounts of sterile water in to the airway and gently suctioning it back into the bronchoscope (bronchoalveolar lavage) collects cells.

In this study, researchers plan to perform these tests on patients with asthma and normal volunteers. This research may help to improve the understanding of the processes involved in airway inflammation and asthma....

Study Overview

• Status: Recruiting
• Conditions: Asthma

Detailed Description

This tissue procurement protocol proposes to perform bronchoscopy with bronchoalveolar lavage, bronchial brushings, and bronchial wall biopsies, as well as to collect samples of sputum, exhaled breath condensates and blood, in order to evaluate the molecular mechanisms underlying the pathogenesis of airway inflammation, airway hyperresponsiveness, and airway remodeling in asthmatic subjects.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Stewart J Levine, M.D.; Phone Number: (301) 402-1553; Email: levines@nhlbi.nih.gov
• Study Contact Backup: Name: Joni Y Mills, C.R.N.P.; Phone Number: (301) 402-6623; Email: joni.mills@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Any individual between the ages of 18 and 75 with asthma will be accepted into the study. Since asthma has a roughly equivalent prevalence in groups differing in race and gender, recruitment of study participants will be aimed at selecting a study population which reflect this diversity. Asthmatic or research volunteers with HIV infection will be excluded from the study so as not to include patients with HIV-related lymphocytic airway inflammation. Volunteers will be obtained through the NIH Clinical Research Volunteer Program or other standard channels at NIH.

Description

• INCLUSION CRITERIA:

ASTHMATICS:

1. Patients undergoing a research bronchoscopy will be between 18 and 75 years of age, male or female. The diagnosis of asthma requires a history of intermittent, reversible expiratory flow limitation. In addition, patients will have demonstrated evidence of either an abnormal methacholine challenge or reversible airway obstruction. An abnormal methacholine challenge will be defined as a decrease in FEV1 of at least 20% at a PD20 dose < 200 microgram. Reversible airway obstruction will be defined as an improvement of at least 10% in either the FEV1 or FVC following bronchodilator treatment. Methacholine challenge testing will not be performed if the subject has a history of allergy to methacholine. Results of testing performed by the subject s primary care provider may be accepted as evidence of reversible airflow obstruction.

2. For women of childbearing potential, negative pregnancy test and willingness to adhere to reliable birth control methods prior to

   bronchoscopy or sputum induction.

3. Asthmatic research subjects who will only be providing research blood specimens, nasal epithelial lining fluid, spontaneously expectorated sputum, or exhaled breath condensate, and will not be undergoing a research bronchoscopy or sputum induction, may participate in the protocol by providing a clinical history that they have asthma and are not pregnant. Documentation of an abnormal methacholine challenge or reversible airflow obstruction or a negative pregnancy test, for women of childbearing age, will not be required for donation of research blood specimens, or other non-invasive samples, such as nasal epithelial lining fluid, sputum, or exhaled breath condensate.

EXCLUSION CRITERIA:

ASTHMATICS:

Diagnosis of a pulmonary disorder other than asthma (e.g., chronic bronchitis, cystic fibrosis, HIV-related lymphocytic airway inflammation).

History of drug or alcohol abuse within the past year.

Positive test for human immunodeficiency virus (to exclude patients with HIV-related lymphocytic airway inflammation) or hepatitis virus.

INCLUSION CRITERIA - RESEARCH VOLUNTEERS:

1. Research volunteers undergoing a research bronchoscopy will be between 18 and 75 years of age, male or female.
2. A negative inhalational methacholine challenge as defined by the absence of a 20% decrease in FEV1 at a PD20 dose of > 400 microgram (normal bronchial hyperresponsiveness). Methacholine challenge testing will not be performed if the subject has a history of allergy to methacholine. Results of testing performed by the subject s primary care provider may be accepted as evidence of a negative methacholine challenge.
3. For women of childbearing potential, negative pregnancy test within 2 weeks prior to bronchoscopy and willingness to adhere to reliable birth control methods prior to bronchoscopy or sputum induction.
4. Research volunteers who will only be providing research blood specimens, nasal epithelial lining fluid, sputum, spontaneously expectorated sputum, or exhaled breath condensate, and will not be undergoing a research bronchoscopy or sputum induction, may be included in the protocol without documentation of a negative inhalational methacholine challenge or a negative pregnancy test if they provide a history that they do not have asthma and that they are not currently pregnant, for women of childbearing age.

EXCLUSION CRITERIA - RESEARCH VOLUNTEERS:

Same as the asthmatic exclusion criteria plus a history of asthma.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; Asthmatics
2; Research Volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the role of apolipoprotein and lipid pathways in asthmatic and non-asthmatic subjects.	These studies will increase the understanding of the pathogenic mechanisms underlying asthmatic airway inflammation and may identify novel therapeutic targets.	ongoing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the role of exosome-associated proteins and receptors in the regulation of airway inflammatory responses	These studies will increase the understanding of the pathogenic mechanisms underlying asthmatic airway inflammation and may identify novel therapeutic targets.	ongoing
Assess the expression, regulation, and function of differentially expressed proteins and genes in human airway structural and inflammatory cell populations in asthma	These studies will increase the understanding of the pathogenic mechanisms underlying asthmatic airway inflammation and may identify novel therapeutic targets.	ongoing
Assess the relative contribution of specific soluble pro-inflammatory cytokines and receptors in asthmatic bronchoalveolar lavage fluid (BALF) in mediating airway structural and inflammatory cell responses	These studies will increase the understanding of the pathogenic mechanisms underlying asthmatic airway inflammation and may identify novel therapeutic targets.	ongoing
Assess the expression, regulation, and function of proteins regulating the release of soluble receptors and mediators from asthmatic inflammatory and structural cell populations	These studies will increase the understanding of the pathogenic mechanisms underlying asthmatic airway inflammation and may identify novel therapeutic targets.	ongoing

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Stewart J Levine, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 1999

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimated): November 4, 1999

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: January 16, 2024

More Information

Terms related to this study

• Keywords: Natural History; Bronchoscopy; Induced Sputum; Exhaled Breath Condensate; mRNA; Fiberoptic Bronchoscopy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 990076; 99-H-0076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No