Natural History of Bronchiectasis

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. Often bronchiectasis can
be associated with chronic infections from environmental germs such as the nontuberculous
mycobacteria.

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 and on their chronic infections like the
nontuberculous mycobacteria. As potential novel therapies develop, participants may be
offered the opportunity to participate in clinical treatment trials.

- 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 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 stored

INCLUSION CRITERIA FOR RELATIVES:

As a part of this protocol we may obtain blood, sputum, urine, or buccal swabs from some
blood relatives of patients on the study, with the hope of isolating and characterizing the
primary host defense defect(s) or genetic links responsible for airway infection
susceptibility and/or bronchiectasis seen within families. Male and female relatives will
be accepted without limitation due to age. These relatives may have pertinent
disease-related history obtained, but will neither receive treatment nor have any other
protocol procedures done unless they are enrolled on the study.

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.

When a pediatric subject reaches age 18, continued participation will require reconsenting
with the adult consent document.