Defining and Treating Depression-related Asthma
Condition: Asthma; Depression; Childhood Asthma
MeSH terms: Asthma; Depression; Depressive Disorder
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Depression is seen more often in people with asthma, and may lead to increased development
      and severity of asthma.

      This study will investigate whether children with depression and asthma have less allergic
      disease and less inflammation than children with asthma who do not have symptoms of
      depression.

      The study will also investigate whether the lungs of children with depression and asthma
      respond to an anticholinergic inhaler called ipratropium more than the lungs of non-depressed
      asthmatic children.
    

Detailed description: 
      It is well accepted that asthma is not a single uniform disease, but rather many different
      disease sub-entities with different etiologies and pathophysiologies. The term "endotype" was
      coined to delineate distinct subtypes of asthma; an "endotype" specifically is as "a subtype
      of a condition, which is defined by a distinct functional or pathophysiological mechanism".
      The division of asthma into endotypes is critical to the development of targeted
      immunomodulators and other specific treatment modalities to more effectively treat the
      diverse asthmatics encountered in clinical practice.

      There is a clear association between depression and asthma, with evidence suggesting that
      depression leads to increased development of asthma rather than the reverse. If, as
      suggested, depression truly mediates a subset of asthma, this depression-related asthma
      "endotype" has not been well characterized to date. A promising theory of the
      pathophysiological mechanism of depression-related asthma is that of autonomic nervous system
      dysregulation associated with depression leading to airway compromise (Miller and Wood,
      2003). Specifically, depression is associated with excess parasympathetic (cholinergic)
      activation, and cholinergic activation can mediate bronchoconstriction through the action of
      acetylcholine on the muscarinic receptors on bronchial smooth muscle. It has been
      demonstrated that during emotional stimuli, depressed children with asthma have increased
      parasympathetic activation, which associates with increased airway resistance. In contrast,
      when experiencing these same emotional stimuli, non-depressed children with asthma have
      increased sympathetic activation.

      The investigators anticipate that depressed child asthmatics have cholinergically-mediated
      bronchoconstriction as a major mediator of their disease activity. Based upon studies of
      depressed asthmatic children showing increased parasympathetic/cholinergic reactivity in
      response to laboratory based emotional stimuli, along with a recent study showing that
      depressed asthmatic adults have decreased bronchodilatory response to beta-agonists, the
      investigators hypothesize that asthmatic children with higher depressive indices will have
      more bronchodilatory response on spirometry following treatment with a short-acting inhaled
      anticholinergic, and less additional bronchodilation with an inhaled beta-agonist, compared
      to children with lower depressive indices. The investigators will set out to demonstrate if
      during an episode of bronchoconstriction, depressed child asthmatics will achieve more
      bronchodilation from a short-acting inhaled anticholinergic than will non-depressed child
      asthmatics.

      The investigators next predict that with excess cholinergic activation as a cause of
      bronchoconstriction in depressed pediatric asthmatics, there will be less atopic
      sensitization and Th2-mediated inflammation driving the airway disease in this subset of
      asthmatics. The investigators hypothesize that, compared to non-depressed child asthmatics,
      depressed pediatric asthmatics during an episode of bronchoconstriction will show less
      evidence of airway inflammation as measured by fractional exhaled nitric oxide (FeNO) and
      peripheral blood eosinophilia, and will have lower rates of atopic sensitization measured by
      skin prick testing to environmental allergens and/or elevated total serum immunoglobulin E
      (IgE). In addition, the investigators will assess patient-identified asthma triggers, which
      are anticipated to be different in the depressed asthmatic group, with increased
      identification of emotions and cold weather as triggers, and less identification of allergens
      as triggers.
    

Intervention name(s): Ipratropium Bromide
Intervention type(s): Drug
Intervention description(s): All subjects receive inhaled ipratropium once with measurement of spirometry before and after. Bronchodilator response of subjects with depression is compare to that of subjects without depression.
Intervention MeSH terms: Bromides; Ipratropium
Intervention model: Single Group Assignment
Intervention model description: Children with asthma and depression versus children with asthma without depression are compared for presence of allergies, airway inflammation, and response to bronchodilation with ipratropium.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: asthma; depression; anticholinergic therapy