Exhaled Breath Condensate as a Measure of Airway Inflammation in Children With Asthma
Condition: Asthma
MeSH terms: Asthma; Inflammation
Study type: Observational

Summary: 
      This study will evaluate the usefulness of a new procedure for evaluating asthma in children.
      The method measures the pH (a measure of acidity and alkalinity) of exhaled breath condensate
      (water vapor created by the lungs). The condensate contains products of the lungs that may be
      associated with lung inflammation. Investigators will determine if the pH of the exhaled
      breath condensate correlates well with known asthma indicators, such as number of
      hospitalizations, school absenteeism, use of rescue medication, and others. Test results will
      be compared with findings from healthy normal volunteers. No experimental treatments or
      medicines are used in this study. Patients who require treatment for their asthma will
      receive standard care with medicines approved by the Food and Drug Administration and used
      widely in the United States.

      Children with asthma and healthy normal volunteers between 6 and 17 years of age may be
      eligible for this study. You must complete the study before your 18th birthday. Candidates
      are screened with a medical history and physical examination.

      Children with asthma undergo the following tests and procedures over six clinic visits,
      including an initial visit and follow-up visits at 4-8 weeks, 3, 6, 9, and 12 months:

        -  Blood draw in children over 6 years of age. Medications are available to decrease the
           pain associated with blood drawing.(initial visit)

        -  Allergen skin testing: Drops of up to 16 allergens are placed on the arm. The skin under
           each drop is scratched and the area is observed for an allergic reaction. (4- 8-week
           follow-up visit)

        -  Expired nitric oxide testing: The child breathes into a balloon to collect a portion of
           the gases exhaled form the lungs. This test measures the amount of nitric oxide, which
           correlates with bronchial inflammation. (all visits)

        -  Exhaled breath condensate: The child breathes into a plastic tube surrounded by a cold
           metal sleeve for 10 to 15 minutes. The water vapor created by the lungs (the same vapor
           that forms when breathing outside on a cold day) is collected and the pH measured. (all
           visits)

        -  Pulmonary (lung) function test: The child blows very hard into a tube attached to a
           machine to measure the airflow from the child's lungs. This test measures airflow from
           the lungs. (all visits) The children are given small plastic device called a peak flow
           meter - a device used to measure lung function - to use at home. Children whose lung
           function is less than 80% of the predicted value for their age may be given medicine to
           see if their lung function improves.

        -  Review of the patient's symptoms, sick days, medicines or actions taken to get over the
           illness; review of peak flow reports; and review of action plan. (3-, 6-, 9-, and
           12-month visits)

      Healthy controls will have the expired nitric oxide test, exhaled breath condensate test, and
      pulmonary function test at each visit at the initial and over two additional visits scheduled
      6 months apart.
    

Detailed description: 
      The onset of asthma is often during childhood, and when the child is atopic, it is more
      likely to persist into adulthood. Diseases such as asthma have a higher prevalence in
      childhood; and management that alters the morbidity of allergic disease in children may
      impact disease outcomes in future years.

      Asthma is the most prevalent chronic disease in childhood and accounts for the highest rate
      of hospitalizations in the ages between 0-4 years. Unfortunately, there are few noninvasive
      objective measurements of pulmonary health in children. Current techniques include
      determination of peak flow, spirometry, and measurement of nitric oxide (NO). Bronchial
      inflammation is a central feature of asthma and anti-inflammatory therapy is the mainstay of
      treatment. Expired NO (eNO) has been shown to correlate with bronchial inflammation. However,
      the collection of NO has only been available in research settings due to the limitations of
      collection and analysis. In contrast, exhaled breath condensate (EBC) is easily obtained and
      pH analysis technically simple.

      Determination of pH in EBC is a novel, non-invasive technique in clinical study as a means to
      evaluate the severity of pulmonary inflammation. In the protocol described, we will evaluate
      the utility of EBC in the measurement of airway disease in 60 children with asthma and
      compare them to 30 healthy cohorts in the same age range. We will determine if EBC pH is
      reflective of the degree of morbidity in children by correlating measurements with known
      parameters of disease including: 1) number of hospitalizations, 2) absenteeism from school,
      3) number of asthma exacerbations, 4) loss of work days (if applicable), 5) extent of rescue
      medication usage, 6) spirometry to evaluate obstruction, and 7) NO as a measurement of
      inflammation.

      Subjects will be evaluated and then categorized based on the National Asthma Education and
      Prevention Program (NAEPP) guidelines. We will measure the pH from EBC in children age 6 to
      less than 18 years of age and compare findings to clinical data, spirometry, and expired NO.
      In this way, we will determine if EBC is a potentially useful non-invasive measurement of
      airway disease. It is hoped that measurements of EBC will be helpful in identifying those
      children in which the addition of an anti-inflammatory medication is appropriate. We will
      also attempt to measure inflammatory mediators to determine if they can be used to assess
      inflammation.

      This method may also be useful in detecting airway inflammation due to an infectious agent
      before a systemic reaction (fever, respiratory distress, or cough) is apparent in children
      with various immunodeficiency diseases such as chronic granulomatous disease (CGD), recurrent
      respiratory infections without a defined host defect (RIND), or Job's syndrome.

      We will recruit 30 healthy control children in the same age range to compare the EBC pH
      values in children without allergic or other chronic pulmonary diseases. In addition, we will
      recruit 30 children (10 in each group) with CGD, RIND, and Job's to compare exhaled breath
      condensate pH and exhaled nitric oxide values to those from children with allergic airway
      inflammation to determine if these methods are useful for early diagnosis of infectious
      airway inflammation.
    

Keywords: Pediatric; Non-Invasive; Anti-Inflammatory; pH; Mediators; Asthma; Childhood Asthma; Healthy Volunteer; HV