Cross-sectional Characterization of Idiopathic Bronchiectasis
Condition: Infection; Bronchial Diseases; Respiratory Tract Diseases
MeSH terms: Bronchiectasis; Respiratory Tract Diseases; Bronchial Diseases
Study type: Observational

Summary: 
      Background:

      - Bronchiectasis is a type of lung condition in which the lungs airways are abnormally
      stretched and widened. This stretching and widening makes it difficult for mucus and other
      substances to move out of the lungs, encouraging the growth of bacteria and leading to
      breathing problems or infection. Bronchiectasis can be caused by genetic disorders or
      diseases such as tuberculosis or rheumatoid arthritis. Researchers are interested in
      developing better ways to diagnose and treat a lung problem called idiopathic or unexplained
      bronchiectasis.

      Objectives:

      - To better describe the physical characteristics, radiographic patterns, and airway
      microbiology of unexplained bronchiectasis and to look for possible genetic links or risk
      factors.

      Eligibility:

        -  Individuals at least 18 years of age who have a chronic cough and who have had a CT scan
           that has revealed signs of bronchiectasis.

        -  Current smokers or those who have smoked for at least 10 years, as well as individuals
           who have known causes of bronchiectasis or who have had organ transplants, are not
           eligible to participate.

      Design:

        -  Participants will have one outpatient clinic visit for evaluation with a physical
           examination including detailed body size measurements and medical history and for
           collection of blood samples for routine lab tests and genetic analyses and a chest x-ray
           if no recent one is available.

        -  Participants will also have tests of lung function, and measurement of a gas called
           nitric oxide in the nose. Participants whose initial tests show abnormal results may
           also be asked to have a nasal scrape to collect cell samples and/or a skin sweat test to
           measure salt concentrations.

        -  Participants will also have a sputum specimen collected during the visit and will be
           asked to collect two additional early morning sputum samples and a mouth rinse at home
           within 2 weeks of the clinic visit, and mail the sample collection materials to the
           research team.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Adults with idiopathic bronchiectasis, with stratification by gender and by
        presence/absence of respiratory infection with nontuberculous mycobacteria (NTM)
      
Keywords: Rare Disease of Airways; Chronic Cough; Nontuberculous Mycobacteriam Infection; Natural History; Bronchiectasis; Idiopathic Bronchiectasis