Neurostimulation for Asthma

Introduction

When one considers electricity a digital drug , it becomes evident that any innervated organ should be amenable to neuromodulation. The field of neuromodulation is expanding greatly, with novel targets constantly being explored, from cardiac disease to urinary incontinence. Spinal cord stimulation (SCS) for pain and deep brain stimulation (DBS) for motor dysfunction, such as Parkinson’s disease, are considered mainstream therapies for those disorders. Novel neuromodulatory targets that include the pulmonary system, previously not thought to be amenable to neuromodulation interventions, are under study.

Vagus nerve stimulation (VNS), which has been used to treat epilepsy since the 1990s, is being considered for people with a variety of disorders such as headaches, inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease, neurologic disorders including anxiety, depression, and posttraumatic stress disorder, sleep disorders, fibromyalgia, stroke, bleeding diatheses, metabolic disorders such as diabetes mellitus, and airway reactivity. Historically, disorders associated with these diseases have not been considered amenable to neurostimulation.

Asthma: The Scope of the Problem

Asthma is a chronic, long lasting, inflammatory disease of the lung and airways, characterized by reversible bronchoconstriction in response to noxious stimuli. This is mediated by airway smooth muscle contraction and the release of mucus, which leads to airway narrowing. Asthma is classically considered to have both an inflammatory and a neural component. In stress-induced asthma for example, an anxiety attack will trigger the release of histamine and leukotrienes, which can trigger the narrowing of airways ( ). Local anesthetics can be used to blunt airway reactivity, when administered either locally or systemically ( ).

Asthma and airway reactivity is an enormous problem. In recent decades, both asthma prevalence and incidence have been increasing worldwide. According to the World Health Organization, asthma affects over 334 million people worldwide. In the United States, per the National Health Interview Survey (NHIS)-2012, about 26 million people (8%) suffer from current asthma. It is the most common chronic disease in childhood, affecting an estimated 7 million children. Asthma is a significant public health problem, which often requires the use of emergency care, sometimes including hospital admission, and is responsible for a high number of missed school and/or workdays. Two-hundred and fifty thousand annual deaths are attributed to the disease. According to the Centers for Disease Control, asthma costs the American economy 56 billion dollars each year.

Traditional treatments for asthma include beta agonists and inhaled and systemic steroids. There are emerging biologic therapies targeting cytokines and cytokine receptors. None of these treatments work exceedingly well, and systemic steroids, which have significant systemic side effects, should only be used in later stages of the disease. An approach that could rapidly and sustainably reduce bronchoconstriction has the potential to revolutionize the treatment of bronchoconstriction and improve the quality of life for millions with asthma. Previously published literature, in a variety of species, support investigation of VNS with the interplay of neural pathways and receptors that control airway smooth muscle tone.