Cross-sectional Characterization of Idiopathic Bronchiectasis

The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) is comprised of 6 geographically-dispersed clinical research sites designed to study chronic disorders of the conducting airways associated with bronchiectasis. The first Clinical Center protocol (06-I-0217) focused on airway diseases with a known genetic etiology: primary ciliary dyskinesia (PCD), variant cystic fibrosis (vCF), and pseudohypoaldosteronism (PHA). This second GDMCC protocol will study adult patients with non-CF, idiopathic bronchiectasis, whose genetic etiologies are not known. Patients will receive the same level of rigorous testing that has allowed proper diagnosis of patients with PCD, vCF, and PHA. Idiopathic bronchiectasis is reportedly more common in females with certain asthenic morphotypes and associated with environmental organisms, such as nontuberculous mycobacterium (NTM). Gender predilection due to referral bias is unclear. Other susceptibility factors predisposing to bronchiectasis or acquisition of NTM are also unclear. The study will attempt to broaden the understanding of this disease by comparing gender-associated factors and NTM status. A relatively equal number of both females/males and NTM/non-NTM infected subjects will be accrued. Patients will be stratified by gender and by the presence/absence of respiratory infection with NTM. Approximately 300 people may be screened to find 260 eligible subjects since a small number (e.g., 40 patients) may be diagnosed with PCD, vCF, or other known etiology as an explanation for the bronchiectasis. This single-visit protocol will use a systematic approach to characterize the clinical, morphological, radiological, and microbiological phenotypes of idiopathic bronchiectasis. Physical features, radiographic patterns, and associated lower airway microbial flora will be assessed. There is no natural history of disease course follow-up component to this protocol. The standard evaluation includes a quantitative assessment of body morphometrics, functional assessments of pulmonary physiology, nasal nitric oxide measurement with subsequent detailed assessment of ciliary structure and motility in selected patients, quantitative immunoglobulins levels to screen for humoral immune defects, and selected genetic analysis of candidate alleles, such as CFTR and A1AT. Genotype/phenotype correlations will be researched and possibly defined. Careful evaluation and characterization of these phenotypes will guide the genetic characterization of idiopathic bronchiectasis, and likely lead to an improved diagnostic approach. Identification of disease causing genes may provide new therapeutic targets.