Effect of Fasting on the Asthma Inflammasome
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      Background:

      Research shows that restricting calories has a positive effect on immune cell health in
      healthy people. Researchers want to learn if it will help people with asthma. They want to
      better understand how the body s immune response and lung function responds to short-term
      calorie restriction. For this, they want people to fast (no food or drink except water) for
      24 hours.

      Objective:

      To explore the benefits of calorie restriction in people with asthma.

      Eligibility:

      Healthy people ages 18 to 60 who have a history consistent with asthma and prior
      documentation of airflow obstruction or wheezing.

      Design:

        -  Participants who have taken part in asthma research at NIH will be screened with a
           telephone interview. All other participants will have a medical history, blood tests,
           and physical exam.

        -  Eligible participants will return to the NIH Clinical Center one morning for 2 hours.
           They will be fed breakfast. They may have blood and urine tests.

        -  Participants will then fast for 24 hours.

        -  Participants will return to the Clinical Center the next morning for 4 hours. They will
           have blood drawn. They will eat breakfast and then repeat blood draws 2.5 hours later.
           They will have a urine test.

        -  Blood and urine tests will be done at the end of the fast and after the meals to confirm
           that the participant fasted for the full 24-hour period.

        -  Participants will have lung function tests and exhaled gas measurements. A machine will
           measure the volume of air they can breathe out. Some gases in the breath increase with
           inflammation. Participants will breathe into a machine that analyzes the gases in their
           breath.
    

Detailed description: 
      The NLRP3 inflammasome is part of the innate immune system that can be activated by
      atherosclerosis, gout and diabetes (sterile inflammation). As mitochondrial signaling can
      trigger the NLRP3 inflammasome, we initially proposed that fasting, via a nutrient-sensing
      mitochondrial program, would dampen this innate immune program. Our preliminary data shows
      that a 24-hour fasting does blunt NLRP3 inflammasome activation in healthy young individuals.
      Interestingly, this inflammasome program has been implicated in the pathophysiology of
      bronchoreactivity linked to asthma and intermittent fasting has been found to reduce disease
      exacerbations in asthmatic patients. The objective of this protocol will extend our
      investigations, from what we are finding in young control normal volunteers, to enable us to
      investigate stable mild-moderate asthmatic subjects to determine whether fasting can blunt
      inflammasome activation and assess whether this transient nutrient-deprivation maneuver can
      improve airflow. Blood samples and pulmonary function testing to assay the immune response
      and bronchoreactivity will be performed in subjects in response to a 24-hour fast (water
      intake will not be restricted) followed by re-testing 3 hours after a fixed caloric meal. The
      objective of this pilot study is to identify if these immune adaptive pathways can be subdued
      in human subjects with a known inflammasome linked disease. Additionally, this study may
      enable us to identify a potential therapeutic pathway to blunt/negate inflammation associated
      with nutrient-excess associated bronchoreactivity of asthma.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        -Males and females between the ages of 18 and 60@@@-Asthmatic subjects will have a history
        consistent with asthma, be on chronic asthma therapy and have prior documentation of
        reversible airflow obstruction based upon either a positive response to an inhaled
        bronchodilator or a positive methacholine broncho-provocation challenge test@@@@@@
      
Keywords: Asthma; Inflammasome; Fasting; Airflow Obstruction