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The Nervous System as Potential Targets for Asthma Treatments

Lessons Learned from a Centennial History of Asthma Research

The University of Texas Medical Branch Galveston, Texas

To the Editor:

The review article on the centennial history of asthma research points to what may be a major limitation of the current research approach to asthma drug discovery: exclusive focus on the cellular inflammatory and immunologic mechanisms with little research on the neurogenic mechanisms (1). With up to 40% of patients with asthma remaining symptomatic despite current treatment approach, Drs. Walter and Holtzman's article (A centennial history of research on asthma pathogenesis. Am J Respir Cell Mol Biol. 2005;32:483–489) is a stark reminder of the need to move beyond cellular inflammation and explore neurologic mechanisms as potential targets for asthma treatment (1, 2).

The concept of treating asthma as a "neuropathic" disease is not new (3–5). Indeed, 37 years ago Sayar and Polvan reported a subgroup of patients with severe bronchial asthma, whose symptoms responded to anti-epileptic drugs, leading to a decrease in anti-asthmatic drug use and fewer asthma exacerbations (3). This line of research has laid dormant in favor of almost exclusive focus on inflammatory and immune mediator–based approaches to asthma treatments, despite evidence indicating possible neuropathic mechanisms in asthma. An example of such evidence is the common pathogenic mechanism shared by neuropathic pain disorders (such as postherpetic neuralgia) and asthma (6, 7). Such mechanisms include changes in the sodium and calcium channels properties of the central autonomic neurons; abnormal synaptic transmission; pathologic activation of sensory nerve endings (especially the C-fibers) by irritants such as infections and injury; and release of monoamines, glutamate, -aminobutyric acid, substance P, neurokinin A, and other mediators (6, 7). Other evidence in support of the neurogenic paradigm of asthma includes preliminary reports of the beneficial effects of neuropathic pain drugs in subtypes of patients with asthma (3–5). For example, in a clinical trial of carbamazepine and sodium valproate in patients with moderate-to-severe asthma, Lomia and colleagues reported a complete remission of asthma symptoms in 21 of the 28 subjects, paralleling improvement in the peak-flow rates and subsequent discontinuation of pretrial anti-asthma drugs (4). The preliminary findings in this study and others suggest a critical role for central and peripheral nervous system mechanisms in the pathophyiology of asthma and other reactive airway diseases.

It is high time we expand the current research on cellular mediator and inflammation-based paradigms to central and peripheral neurological mechanisms as potential targets for asthma treatment. The review of centennial history of asthma research gives us a glimpse of how far we can go by investigating all pathogenic paradigms as potential targets for asthma treatment.

Footnotes

Conflict of Interest Statement: M.A.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

References

1. Walter MJ, Holtzman MJ. A centennial history of research on asthma pathogenesis. Am J Respir Cell Mol Biol 2005;32:483–489.[Free Full Text]
2. Heaney LG, Robinson DS. Severe asthma treatment: need for characterising patients. Lancet 2005;365:974–976.[CrossRef][Medline]
3. Sayar B, Polvan O. Epilepsy and bronchial asthma. Lancet 1968;1:1038.
4. Lomia M, Chapichadze Z, Pruidze M, Platonov P. Efficacy of monotherapy with carbamazepine and valproic acid in patients with bronchial asthma: is asthma a neurological disease? The Internet Journal of Neurology 2005;4:1. Accessed on June 10, 2005 http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijn/vol4n1/asthma.xml
5. Jain S, Jain KC. Effect of phenytoin sodium in the management of poorly controlled bronchial asthma at a rural health center in Phalodi, Rajasthan, India. J Asthma 1991;28:201–211.[Medline]
6. Groneberg DA, Quarcoo D, Frossard N, Fischer A. Neurogenic mechanisms in bronchial inflammatory diseases. Allergy 2004;59:1139–1152.[CrossRef][Medline]
7. Harden RN. Chronic neuropathic pain: mechanisms, diagnosis, and treatment. Neurologist 2005;11:111–122.[Medline]

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