Natural History of Bronchiectasis

Bronchiectasis is a chronic inflammatory and muco-obstructive condition that results in abnormal dilation of the airways, decline in lung function, frequent exacerbations, and chronic respiratory tract infections. Cystic fibrosis (CF) is the most well studied genetic condition that causes bronchiectasis. Tremendous strides made in understanding the mechanisms of CF have led to a multitude of novel treatment strategies that have revolutionized the field. In contrast, the mechanisms of other causes for bronchiectasis remain undetermined and the disease-specific treatments for cystic fibrosis are not effective for non-CF bronchiectasis. Bronchiectasis not caused by CF carries a substantial socioeconomic burden, is a lifelong condition with no cure and, in most cases, has no identifiable cause. Prioritizing research in this important respiratory disease is essential because it affects individuals from children through older adulthood.

Background:

This protocol is aimed at exploring underlying causes and mechanisms for the development of bronchiectasis. Participants will undergo testing based on their individual clinical presentations to identify underlying causative factors. Additionally, some patients will be followed over time to better understand the natural history of evolving bronchiectasis and to assess the effect of management strategies on the course of the disease and on their chronic infections like the nontuberculous mycobacteria. As potential novel therapies develop, participants may be offered the opportunity to participate in clinical trials.

Objectives:

The primary objective of this study is to identify causes and/or underlying conditions associated with bronchiectasis.

Eligibility:

• Individuals 5 years of age and older who have an established diagnosis of bronchiectasis or a history of chronic/recurring respiratory infections.
• Direct family members (e.g., parents, siblings, children) of patients in the study may also be asked to participate.

Design:

• Potential participants will be screened with an initial clinic evaluation and full medical history, as well as a general quality of life and respiratory symptom questionnaire.
• The following standard procedures may be done as part of the study: air sampling from the nose; imaging studies, which may include an x-ray or computed tomography (CT), lung function tests; and collection of samples of blood, urine, and sputum (phlegm or mucus). Other tests may be performed as required by the researchers, and will be explained to patients as needed.
• Both patients and relatives (if asked to participate) will provide the following samples: blood or buccal (cheek swab) cells for genetic testing, sputum, and urine.
• To prevent infections and potential disease progression, patients may receive standard medical care and treatment for bronchiectasis and related infections during this protocol.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis; Common Variable Immunodeficiency; Cystic Fibrosis; Autoimmune Disease

Detailed Description

Bronchiectasis is a chronic inflammatory and muco-obstructive condition that results in abnormal dilation of the airways, decline in lung function, frequent exacerbations, and chronic respiratory tract infections. Cystic fibrosis (CF) is the most well studied genetic condition that causes bronchiectasis. Tremendous strides made in understanding the mechanisms of CF have led to a multitude of novel treatment strategies that have revolutionized the field. In contrast, the mechanisms of other causes for bronchiectasis remain undetermined and the disease-specific treatments for cystic fibrosis are not effective for non-CF bronchiectasis. Bronchiectasis not caused by CF carries a substantial socioeconomic burden, is a lifelong condition with no cure and, in most cases, has no identifiable cause. Prioritizing research in this important respiratory disease is essential because it affects individuals from children through older adulthood, including those covered by Medicare.

• Study Type: Observational
• Enrollment (Estimated): 900

Contacts and Locations

• Study Contact: Name: Chevalia J Robinson, R.N.; Phone Number: (301) 496-3973; Email: robinsoc1@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: 5 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children age 5 years and above and adults referred to the NIH with chronic or recurring respiratory infections and/or bronchiectasis will be eligible for participation. Relatives including 5 years and above.

Description

• INCLUSION CRITERIA:

  1. Children age 5 years and above and adults referred to the NIH with chronic or recurring respiratory infections and/or bronchiectasis will be eligible for participation.

  2. Males and females will be considered without regard to race or ethnicity or upper age limit.

  3. Emphasis will be primarily on non CF bronchiectasis for elucidation of mechanisms bronchiectasis development and infection susceptibility. However, select patients with cystic fibrosis or acquired immune defects (such as HIV) may be studied if relevant host defects are suspected, if needed for comparison purposes, or to evaluate and study the management of chronic pathogen associated conditions such as nontuberculous mycobacterial infections or allergic bronchopulmonary aspergillosis.

  4. Subjects must have a primary or referring physician

  5. Subjects must be willing to have samples (blood, tissue, sputum, and stool) stored

  6. Inclusion Criteria for Relatives including children ages 5 years and above; relatives without a known diagnosis of bronchiectasis, including those who are asymptomatic, may be enrolled if they are willing to complete study assessments. These participants will be used for comparative analyses and/or screening for previously undiagnosed disease.

     INCLUSION OF VULNERABLE PARTICIPANTS

     Rationale for inclusion of children:

     The research that is conducted on this protocol is regulated by Health and Human Services, and in compliance with federal guidelines Title 45 Code of Federal Regulations, Part 46, Subpart D. The groups of children that may be included are:

     Affected minors: Bronchiectasis may have early onset and a significant impact on the lives of these patients. It is important to include this population in our study in order to understand the natural history and progression of this condition in children as they often have physiological differences as compared to adult patients. Affected minors may undergo testing that will be tailored to their specific clinical presentation.

     Minors that are related to affected individuals: Children that are relatives of index patients may not be affected or show symptoms. It is important for relatives including minor relatives to be enrolled in our study, in order to help us identify the possible conditions like pre-bronchiectasis to better understand the mechanism of the disease progression. Unaffected child relatives may only undergo tests that are no greater than minimal risk.

     Rational for inclusion of affected pregnant and or nursing women: Pregnant and or nursing women including pregnant minors may be included in accordance with Federal Regulations at Subpart B of 45 CFR 46. Bronchiectasis-related symptoms and respiratory status may change during pregnancy. Including pregnant participants in this observational natural history protocol will allow the study to capture longitudinal changes in clinical status and other relevant data during pregnancy and the postpartum period.

     Study procedures conducted during pregnancy and breastfeeding will be limited to those determined to pose no more than minimal risk to the participant and fetus or breastfeeding infant. Procedures considered greater than minimal risk -including computed tomography scans, bronchoscopy with bronchoalveolar lavage and endobronchial biopsy, and research blood collection- will not be performed during pregnancy or breastfeeding. These procedures may be completed after the participant is no longer pregnant and, when applicable, has discontinued breastfeeding, in accordance with the protocol and investigator judgment.

     EXCLUSION CRITERIA:

  1. Patients who are unable or unwilling to provide informed consent
  2. Any patient who, in the opinion of the Investigator, is unable or unwilling to comply with regular follow-up or is unlikely to provide pertinent information regarding disease progression or response to treatment may be excluded from longitudinal follow-up.

PARTICIPATION OF CHILDREN:

Children under the age of 5 will be excluded from this protocol due to the difficulty of performing pertinent assays in infants and younger children, difficulty distinguishing significance of respiratory infections which occur commonly in younger children, and the lack of adequate facilities and equipment for management of children younger than 2 years.

Study Plan

How is the study designed?

Design Details

• Observational Models: OTHER
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
1; Children age 5 years and above and adults with chronic or recurring respiratory infections and/or bronchiectasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study is to identify causes and/or underlying conditions associated with bronchiectasis.	We will document the presence of underlying associated conditions such as; a. Variant cystic fibrosis through assessment of sweat chloride.b. Primary ciliary dyskinesia through assessment of nasal nitric oxide production, mucosal scrapes for transmission electron microscopy of ciliary ultrastructure.c. Primary immunodeficiency through measurement of quantitative immunoglobulins, specific antigen responses , and lymphocyte phenotyping. d. Allergic bronchopulmonary mycosis through measurement of total immunoglobulin E (IgE), fungal serologies, and skin test responses.e. Autoimmune disease by screening for associated conditions such as inflammatory bowel disease or rheumatoid arthritis.f. Alpha-1 antitrypsin deficiency by assessment of protein levels, phenotype, and gene type.g. Other diagnoses	Baseline, annually, and optional exacerbation visits, or until they no longer wish to return.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2) Monitor a cohort of bronchiectasis patients to better understand factors associated with progression of disease and to assess outcomes of management and therapeutic strategies	a.<TAB>Patient Global Impression of Severity (PGI-S) b.<TAB>Quality of Life Questionnaire-Bronchiectasis (QOL-B)c.<TAB>Chronic Airways Assessment Test (CAAT) d.<TAB>Bronchiectasis Health Questionnaire (BQH)e.<TAB>Child Chronic Cough-Specific Quality of Life (CC-QOL (7-17 years))f.<TAB>Parent Cough-Specific Quality of Life (PC-QOL Parent completed (2-18 years))g.<TAB>Six-minute walk h.<TAB>Chest CT i.<TAB>Lung function: FEV1%predicted, FVC% predicted, response to bronchodilator, lung volumes, LCI, and DLCOj.<TAB>Lower airway microbiology, as well as novel biomarkers of mycobacteria, antimicrobial resistance and microbial changes on the progression of bronchiectasis. k.<TAB>Inflammatory markers	Baseline, annually, and optional exacerbation visits. or until they no longer wish to return.
1) Define mechanisms and pathophysiology for the development and progression of bronchiectasis	We will also assess the following mechanisms and clinical outcomes:1) Systemic immune, and/or epithelial surface defense mechanisms involved in airway infection susceptibility and/or development of bronchiectasis through the:a.<TAB>Collection and storage of blood, sputum, and stoolb.<TAB>Use and storage of other relevant biologic specimens, such as bronchoalveolar lavage fluid or *endobronchial biopsy specimens of respiratory epithelium	Baseline, annually, and optional exacerbation visits. or until they no longer wish to return.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Lunich A, Radtke AJ, Williams M, Stern JM, Barber DL, Germain RN, Anidi IU. Optimized Workflow for Iterative Bleaching Extends Multiplexity Imaging of Highly Autofluorescent Clinical Samples. J Vis Exp. 2025 Jul 11;(221). doi: 10.3791/67980.

Helpful Links

• <p>NIH Clinical Center Detailed Web Page</p>

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2009

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (Estimated): July 22, 2009

Study Record Updates

• Last Update Posted (Actual): November 2, 2026
• Last Update Submitted That Met QC Criteria: October 30, 2026
• Last Verified: October 28, 2026

More Information

Terms related to this study

• Keywords: Natural History; Primary Ciliary Dyskinesia; Variant Cystic Fibrosis; Bronchopulmonary Mycosis; Airway Infection Susceptibility; Chronic Respiratory Infection
• Additional Relevant MeSH Terms: Ciliopathies; Genetic Diseases, Inborn; Immune System Diseases; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Bronchial Diseases; Pancreatic Diseases; Immunologic Deficiency Syndromes; Congenital Abnormalities; Otorhinolaryngologic Diseases; Abnormalities, Multiple; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliary Motility Disorders; Autoimmune Diseases; Cystic Fibrosis; Bronchiectasis; Common Variable Immunodeficiency
• Other Study ID Numbers: 090172; 09-H-0172

Plan for Individual participant data (IPD)

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

IPD Plan Description

Refer to the DMSP

IPD Sharing Time Frame

Refer to the DMSP

IPD Sharing Access Criteria

Refer to the DMSP

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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