Electrical Treatment Of Bronchial Constriction

Abstract

Devices, systems and methods for treating bronchial constriction related to asthma, anaphylaxis or chronic obstructive pulmonary disease wherein the treatment includes stimulating selected nerve fibers responsible for smooth muscle dilation at a selected region within a patient's neck, thereby reducing the magnitude of constriction of bronchial smooth muscle.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. patent application Ser. No. 11 / 591,340, filed Nov. 1, 2006 which in turn claims the benefit of Provisional Patent Application Nos. 60 / 736,001, filed Nov. 10, 2005; 60 / 772,361, filed Feb. 10, 2006; 60 / 814,313, filed Jun. 16, 2006; and 60 / 786,564, filed Mar. 28, 2006, the entire disclosures of which are hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]The present invention relates to the field of delivery of electrical impulses (and / or fields) to bodily tissues for therapeutic purposes, and more specifically to devices and methods for treating conditions associated with bronchial constriction[0003]There are a number of treatments for various infirmities that require the destruction of otherwise healthy tissue in order to affect a beneficial effect. Malfunctioning tissue is identified, and then lesioned or otherwise compromised in order to affect a beneficial outcome, rather...

AI Technical Summary

Benefits of technology

[0028]The present invention involves products and methods of treatment of asthma, COPD, anaphylaxis, and other pathologies involving the constriction of the primary airways, utilizing an electrical signal that may be applied directly to, or in close proximity to, a selected nerve to temporarily stimulate, block and / or modulate the signals in the selected nerve. The present invention is particularly useful for the acute relief of symptoms associated with bronchial constriction, i.e., asthma attacks, COPD exacerbations and / or anaphylactic reactions. The teachings of the present invention provide an emergency response to such acute symptoms, by producing immediate airway dilation and / or heart function increase to enable subsequent adjunctive measures (such as the administration of epinephrine) to be effectively employed.

[0029]In one aspect of the present invention, a method of treating bronchial constriction comprises stimulating selected nerve fibers responsible for reducing the magnitude of constriction of smooth bronchial muscle to increase the activity of the selected nerve fibers. In a preferred embodiment, the selected nerve fibers are inhibitory nonadrenergic noncholinergic nerve fibers (iNANC) which are generally responsible for bronchodilation. Stimulation of these iNANC fibers increases their activity, thereby increasing bronchodilation and facilitating opening of the airways of the mammal. The stimulation may occur through direct stimulation of the efferent iNANC fibers that produce bronchodilation or indirectly through stimulation of the afferent sympathetic or parasympathetic nerves which carry signals to the brain and then back down through the iNANC nerve fibers to the bronchial passages.

[0030]In one embodiment, the iNANC nerve fibers are associated with the vagus nerve and are thus directly responsible for bronchodilation. In an alternative embodiment, the iNANC fibers are interneurons that are completely contained within the walls of the bronchial airways. These interneurons are responsible for modulating the cholinergic nerves in the bronchial passages. In this embodiment, the increased activity of the iNANC interneurons will cause inhibition or blocking of the cholinergic nerves responsible for bronchial constriction, thereby facilitating opening of the airways.

[0031]The stimulating step is preferably carried out without substantially stimulating excitatory nerve fibers, such as parasympathetic cholinergic nerve fibers, that are responsible for increasing the magnitude of constriction of smooth muscle. In this manner, the activity of the iNANC nerve fibers are increased without increasing the activity of the cholinergic fibers which would otherwise induce further constriction of the smooth muscle. Alternatively, the method may comprise the step of actually inhibiting or blocking these cholinergic nerve fibers such that the nerves responsible for bronchodilation are stimulated while the nerves responsible for bronchial constriction are inhibited or completely blocked. This blocking / inhibiting signal may be separately applied to the inhibitory nerves; or it may be part of the same signal that is applied to the iNANC nerve fibers.

[0033]In another aspect of the invention, a method of treating bronchial constriction includes applying an electrical impulse to a target region in the patient and acutely reducing the magnitude of bronchial constriction in the patient. As used herein, the term acutely means that the electrical impulse immediately begins to interact with one or more nerves to produce a response in the patient. The electrical impulse is preferably sufficient to increase the Forced Expiratory Volume in 1 second (FEV1) of the patient by a clinically significant amount in a period of time less than about 6 hours, preferably less than 3 hours and more preferably less than 90 minutes. A clinically significant amount is defined herein as at least a 12% increase in the patient's FEV1 versus the FEV1 measured prior to application of the electrical impulse. In an exemplary embodiment, the electrical impulse is sufficient to increase the FEV1 by at least 19% over the FEV1 as predicted.

[0036]The electrical impulse(s) are applied in a manner that reduces the constriction of the smooth muscle lining the bronchial passages to relieve the spasms that occur during anaphylactic shock, acute exacerbations of COPD or asthma attacks. In some embodiments, the mechanisms by which the appropriate impulse is applied to the selected region within the patient include positioning the distal ends of an electrical lead or leads in the vicinity of the nervous tissue controlling the pulmonary and / or cardiac muscles, which leads are coupled to an implantable or external electrical impulse generating device. The electric field generated at the distal tip of the lead creates a field of effect that permeates the target nerve fibers and causes the stimulating, blocking and / or modulation of signals to the subject muscles, and / or the blocking and / or affecting of histamine response. It shall also be understood that leadless impulses as shown in the art may also be utilized for applying impulses to the target regions.

Problems solved by technology

While there are a variety of different techniques and mechanisms that have been designed to focus lesioning directly onto the target nerve tissue, collateral damage is inevitable.

In many cases, these medicinal approaches have side effects that are either unknown or quite significant, for example, at least one popular diet pill of the late 1990's was subsequently found to cause heart attacks and strokes.

Unfortunately, the beneficial outcomes of surgery and medicines are, therefore, often realized at the cost of function of other tissues, or risks of side effects.

While the therapeutic results of deep brain stimulation are promising, there are significant complications that arise from the implantation procedure, including stroke induced by damage to surrounding tissues and the neurovasculature.

Smooth muscle surrounding the airways goes into spasm, resulting in constriction of airways.

Over time, this inflammation can lead to scarring of the airways and a further reduction in airflow.

This inflammation leads to the airways becoming more irritable, which may cause an increase in coughing and increased susceptibility to asthma episodes.

For some patients, however, these medications, and even the bronchodilators are insufficient to stop the constriction of their bronchial passages, and more than five thousand people suffocate and die every year as a result of asthma attacks.

Minute amounts of allergens may cause a life-threatening anaphylactic reaction.

Anaphylactic shock usually results in death in minutes if untreated.

Anaphylactic shock is a life-threatening medical emergency because of rapid constriction of the airway.

Brain damage sets in quickly without oxygen.

All of these individuals are at risk of anaphylactic shock from exposure to any of the foregoing allergens.

In addition, anaphylactic shock can be brought on by exercise.

Yet all are mediated by a series of hypersensitivity responses that result in uncontrollable airway occlusion driven by smooth muscle constriction, and dramatic hypotension that leads to shock.

Cardiovascular failure, multiple organ ischemia, and asphyxiation are the most dangerous consequences of anaphylaxis.

Clinical treatment typically consists of antihistamines (which inhibit the effects of histamine at histamine receptors) which are usually not sufficient in anaphylaxis, and high doses of intravenous corticosteroids.

Tragically, many of these patients are fully aware of the severity of their condition, and die while struggling in vain to manage the attack medically.

Unfortunately, prompt medical attention for anaphylactic shock and asthma are not always available.

For example, epinephrine is not always available for immediate injection.

Even in cases where medication and attention is available, life saving measures are often frustrated because of the nature of the symptoms.

Constriction of the airways frustrates resuscitation efforts, and intubation may be impossible because of swelling of tissues.

This cardiovascular stress can result in tachycardia, heart attacks and strokes.

COPD is a progressive disease that makes it hard for the patient to breathe.

COPD can cause coughing that produces large amounts of mucus, wheezing, shortness of breath, chest tightness and other symptoms.

In emphysema, the walls between many of the air sacs are damaged, causing them to lose their shape and become floppy.

This damage also can destroy the walls of the air sacs, leading to fewer and larger air sacs instead of many tiny ones.

This causes the lining to thicken and form thick mucus, making it hard to breathe.

Many of these patients also experience periodic episodes of acute airway reactivity (i.e., acute exacerbations), wherein the smooth muscle surrounding the airways goes into spasm, resulting in further constriction and inflammation of the airways.

Frequent acute exacerbations of COPD cause lung function to deteriorate quickly, and patients never recover to the condition they were in before the last exacerbation.

Similar to asthma, current medical management of these acute exacerbations is often insufficient.

Unlike cardiac arrhythmias, which can be treated chronically with pacemaker technology, or in emergent situations with equipment like defibrillators (implantable and external), there is virtually no commercially available medical equipment that can chronically reduce the baseline sensitivity of the muscle tissue in the airways to reduce the predisposition to asthma attacks, reduce the symptoms of COPD or to break the cycle of bronchial constriction associated with an acute asthma attack or anaphylaxis.

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