Non-inflammatory mechanisms in asthma.

Rationale for Research

Asthma affects one in four children and one in five adults in NZ. Whilst asthma can be managed successfully in many cases, current treatment options (which are primarily focused on inflammation) are not particularly effective in a large proportion of patients (30-50%). Consistent with this, there is an increasing awareness that non-inflammatory pathways, such as neural mechanisms, may also be important, with recent studies suggesting that up to 50% of asthma may not involve airway inflammation. It is clear that neural mediators derived from nerves in the airways may play a role in asthma, including bronchoconstriction, cough and mucus production. Also, autonomic regulation of bronchial tone is almost entirely the result of parasympathetic nervous activity, and targeting this activity using anti-cholinergics may be effective in at least a proportion of asthmatics. Despite this, little research has been conducted on the importance of neural mechanisms in asthma. This study will test the hypothesis that neurogenic dysfunction is a key mechanism in asthma pathogenesis, particularly in asthmatics who have no airway inflammation and for whom current asthma treatment is not effective. It may contribute to a major paradigm shift in concepts of asthma aetiology and is likely to identify novel pathways for effective interventions for all asthmatics.

RELATED PUBLICATIONS

Douwes J, Brooks C, Pearce N. Stress and asthma: Hippocrates revisited. J Epidemiol Community Health, 2010; 64(7): 561-2.
Douwes J, Brooks C, Pearce N. Asthma nervosa: old concept, new insights. Eur Respir J, 2011; 37(5): 986-90.
Brooks C, Gibson P, Douwes J, van Dalen C, Simpson J. Relationship between airway neutrophilia and ageing in asthmatics and non-asthmatics. Respirology, 2013; 18(5): 857–865.
Brooks C, van Dalen C, Zacharasiewicz A, Simpson J, Harper J, Le Gros G, Gibson P, Pearce N, Douwes J. Absence of airway inflammation in a large proportion of adolescents with asthma. Respirology, 2016; 21(3): 460-466.
Brooks C, van Dalen C, Hermans I, Gibson P, Simpson J, Douwes J. Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes. Allergy, 2017; 72(10): 1583-1586.
Ali H, Brooks C, Crane J, Beasley R, Le Gros G, Holgate S, Gibson P, Pattemore P, Tzeng S, Pearce N, Douwes J. Autonomic nervous system activity in adolescent asthma. Respirology, 2020; 25(S1):032.
Ali H, Brooks C, Crane J, Beasley R, Le Gros G, Holgate S, Gibson P, Pattemore P, Stanley T, Tzeng S, Pearce N, Douwes J. Airway sensory nerve sensitivity in adolescents with eosinophilic and non-eosinophilic asthma. Eur Respiratory J, 2020; 56:4081.