Effect of Dietary Supplements With Fish Oil on Mannitol-induced Airway Sensitivity & Inflammation in Persons With Asthma
Condition: Asthma
MeSH terms: Asthma; Inflammation
Study type: Interventional
Phase: Phase 2

Summary: 
      We wish to investigate the effects of 3 weeks of orally administered fish oil supplements on
      the airway sensitivity (provoking dose to cause a 15% fall in FEV1, PD15) to inhaled mannitol
      (AridolTM). Mannitol, an osmotic stimulus has been demonstrated as a useful model for
      exercise-induced asthma. We also wish to investigate if there is any associated improvement
      associated with selected markers of airway inflammation that can be measured in the sputum,
      blood, urine and exhaled breath condensate. Oral fish oil supplements have recently been
      demonstrated to be effective inhibitors of exercise-induced asthma, in association with an
      inhibition of markers of inflammation, over a 3 week treatment period. This finding has
      important implications in the treatment of asthma as this is a faster and more effective
      improvement than what is seen with inhaled corticosteroids on exercise-induced asthma. This
      observation requires validation and further investigation. We wish to study this in two
      patient groups; (a) steroid naïve asthmatics taking beta2 agonist when required and (b)
      asthmatics taking regular inhaled corticosteroids < 1000 mcg/day.
    

Detailed description: 
      Asthma is a chronic inflammatory disorder of the airways characterized by recurrent episodes
      of dyspnea, wheeze and chest tightness and is associated with variable airway obstruction.
      Exercise-induced bronchoconstriction (EIB) is a feature specific to asthma. Exercise testing
      protocols have been developed to identify the presence of asthma as well as to assess asthma
      therapy. Airway narrowing following exercise in persons with asthma is thought to result from
      dry air hyperpnoea-induced dehydration of the airway surface, leading to the release of
      mediators from inflammatory cells residing in the airway. Regular treatment with inhaled
      corticosteroids inhibits the airway response to exercise by decreasing the number of
      inflammatory cells and thus the source of bronchoconstricting mediators. Therefore, a
      decrease in the source of mediator may be the reason for this eventual inhibition of the
      airway response to exercise.

      It has recently been demonstrated that fish oil supplementation in capsule form, taken daily
      over three weeks, provides significant protection against EIB. This protection appears to be
      of equal or greater efficacy than inhaled corticosteroids treatment over a similar period.
      This may have positive implications in the treatment of asthma as inhaled corticosteroids are
      known to have some unwanted side effects. Fish oil supplementation in the high doses given in
      previous studies have not demonstrated any side effects and may lead to an alternative
      treatment, or a decrease in the dose of inhaled steroids required in the treatment of asthma.

      A new bronchial provocation test using inhaled mannitol, derived from the mechanism of EIB,
      has been recently developed and is now registered in Australia and the European Union.
      Mannitol causes airway narrowing in a similar manner to exercise in persons with asthma and
      is effective in identifying responsiveness to inhaled corticosteroids. We wish to use inhaled
      mannitol as a model for EIB in an effort to further investigate the use of fish oil
      supplementation in the treatment of asthma. Our hypothesis is that daily orally administered
      encapsulated fish oil will attenuate the airway response to mannitol over a 3-week treatment
      period. We also wish to measure associated markers of inflammation in the blood, urine,
      sputum and exhaled condensate as well as monitor clinical outcomes such as symptoms and daily
      beta2 agonist use.
    

Intervention name(s): omega-3 fatty acid
Intervention type(s): Drug
Intervention description(s): Pharmaceutical grade fish oil administered daily in the form of 10 capsules (5 capsules b.i.d.) each containing 400mg of eicosapentaenoic acid (EPA) and 200mg docosahexanoic acid (DHA) which will equate to a daily dose of 4000 mg of EPA and 2000 mg or DHA. The matched placebo containing a 50/50 mix of soybean and corn oil will be supplied by the same manufacturer (Ocean Nutrition, Canada)
Other intervention name(s): Meg-3, Product No. 4020EE
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: omega-3 fatty acids; asthma; airway hyperresponsiveness; inflammation