Natural History of Bronchiectasis

Background:

• Bronchiectasis is a disease characterized by airways that are inflamed, abnormally dilated, and chronically infected. Individuals with bronchiectasis have a history of chronic and recurring respiratory infections. Depending on the underlying cause, these infections may involve the entire respiratory tract, resulting in sinus, ear, and lung disease.
• Bronchiectasis continues to be a significant problem in developing countries and in specific groups of individuals, particularly in people who have cystic fibrosis. Although treatments are available or under development for bronchiectasis related to cystic fibrosis, many of the disease-specific treatments may not be effective for bronchiectasis not related to cystic fibrosis.

Objectives:

- To study the natural history of bronchiectasis to identify inherited and immune factors that may explain why certain individuals have chronic recurring infections.

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.
• Patients older than 18 years of age will be invited to join the Bronchiectasis Research Registry, a program supported by the Chronic Obstructive Pulmonary Disease (COPD) Foundation. The purpose of the program is to identify a group of people who are interested in receiving information about research studies focused on bronchiectasis and possibly participating in these research studies. Participants may be offered the opportunity to participate in selected clinic trials related to bronchiectasis or related medical conditions.

Bronchiectasis, or abnormal dilation of the airways, is a condition typically characterized by chronic and recurring respiratory tract infections. Frequently, depending on the underlying cause, these infections involve the entire respiratory tract resulting in sinus, ear, and lung disease. This condition used to be more common in children prior to immunizations for childhood infections. It continues to be a significant problem in developing countries and in specific groups of individuals in the U.S. Cystic fibrosis (CF) is the most commonly associated genetic condition and tremendous strides have been made in recent years in understanding the mechanisms of this disease that are leading to a multitude of emerging novel treatment strategies. The mechanisms of other causes for bronchiectasis have not evolved to this degree, and many of the disease-specific treatments being assessed for cystic fibrosis may not be effective for non-CF bronchiectasis.

This protocol is aimed at exploring associated causes and mechanisms for the development of bronchiectasis in patients with chronic and recurring respiratory tract infections. Participants will undergo testing based on their individual clinical presentations to look for known associated conditions. Additionally, some patients may 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. As potential novel therapies develop, participants may be offered the opportunity to participate in clinical treatment trials.

• Bronchiectasis
• Cystic Fibrosis
• Autoimmune Disease
• Common Variable Immunodeficiency

• Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. Review. No abstract available.
• Morrissey BM, Harper RW. Bronchiectasis: sex and gender considerations. Clin Chest Med. 2004 Jun;25(2):361-72. Review.
• O'Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest. 1998 May;113(5):1329-34.

• PARTICIPANT INCLUSION CRITERIA:

  1. Children age 5 years and above and adults referred to the NIH with chronic or recurring respiratory infections 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 of infection susceptibility. However, select patients with cystic fibrosis or acquired immune defects (such as HIV) may be studied if relevant host defects are suspected or if needed for comparison purposes.
  4. Subjects must have a primary or referring physician
  5. Subjects must be willing to have samples stored

INCLUSION CRITERIA FOR RELATIVES:

Male and female relatives will be accepted without limitation due to age.

PARTICIPANT EXCLUSION CRITERIA:

1. We wish to avoid enrolling subjects, especially children, who have common respiratory problems (aeroallergen sensitivity, asthma, gastric esophageal reflux) that are not associated with an underlying abnormality in host defenses. Evidence of significance of chronic or recurring infections suggestive of an underlying airway surface or systemic host defense defect should be documented by one or more of the following: a) sinus or lower airway cultures positive for bacterial, fungal, or mycobacterial pathogens characteristic of these defects; or b) radiographic evidence of sinusitis with mucosal thickening and/or air-fluid levels; or c) radiographic evidence of bronchiectasis; d) severity of otitis media requiring placement of tympanic membrane pressure equalization tubes; e) severity of sinusitis requiring surgical intervention.
2. Patients who are unable or unwilling to provide informed consent either directly or via appropriately designated surrogate.
3. 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.
4. Children under the age of 5 will be excluded from this protocol.