ASTHMA
Patient Summary:
Asthma causes constriction and inflammation of the airways in the lungs. Asthma may worsen as a result of dust, pet allergies, food allergies, drug allergies, or weather changes. In our clinic, we have had excellent results utilizing STS treatments, primarily designed to create VIP (Vasoactive Intestinal Polypeptide). Medical literature is quoted below showing that this has a broad base in medical knowledge
Physician Summary:
STS treatments are designed to create VIP (Vasoactive Intestinal Polypeptide). It has been documented in medical literature that VIP can reverse and prevent asthmatic changes in the lungs. Hundreds of sections of lung tissue from asthmatic patients and non-asthmatic patients have been compared. It was found that more than 92 percent of the non-asthmatic lung sections had VIP neurons. However, in 468 sections of asthmatic lungs, no VIP neurons were found. This absence of VIP producing neurons would markedly diminish neurogenically mediated bronchodilation. VIP-binding autoantibodies were observed in the plasma of 18% asthma patients. The plasma VIP level in asthmatic patients during acute attack and symptom-free period was significantly lower than that in the patients with bronchitis and the healthy subjects. Utilizing heart rate variability, it has been found that even in normal conditions, when patients are free of asthmatic attack; autonomic nervous function of asthmatics differs from that of normal young adults.
In our clinic, we have had excellent results utilizing STS treatments, primarily designed to create VIP. It has been found that STS treatments cause a normalization of heart rate variability.
MEDICAL JOURNAL BACKGROUND INFORMATION
In a recent study performed by Ernesto Guido, M.D.; it was found that treatment utilizing the Dynatronic STS system successfully decreased the objective signs and subjective symptoms of peripheral neuropathy patients. During that study, daily skin temperatures were obtained from the palmar surface of the thumbs and the plantar surface of the bilateral hallux. It was found in that study that there was a partial or complete normalization of the actual skin temperature and the skin temperature gradient, left to right. (4)
In reviewing that study's results, it could be hypothesized that improved micro- circulation to the nerves resulted in the improvement in the peripheral neuropathy patients. If this is true, then it could be hypothesized that the improvement in the patients' skin temperatures was due to an improved skin microcirculation probably caused by the creation of various neuropeptides by the treatment. It has been shown with laboratory testing that STS treatments have significantly increased the plasma level of
VIP. In addition, heart rate variability (HRV) has been shown to be a reliable indicator of autonomic nervous system function. Therefore, if the STS treatments are improving autonomic nervous system functioning, there should be a corresponding normalizing of the HRV. In our clinic, HRV studies are performed before and after the first STS treatment. With the exception of those patients on significant amounts of narcotics, almost always there is a normalizing of the HRV. This data will result in an upcoming publication.
The current working hypothesis is that the STS treatments are effective due to a combination of the following aspects of the treatments: low frequency electrical current passing through long sections of nerves; electrode pad placement; production of cyclic adenosine monophosphate; the choice of the peripheral nerves being stimulated so that there is a cross-over effect in the Central Nervous System; leakage of action potentials from the nerves being stimulated into nerves entering the sympathetic ganglia; the quadrilateral location of stimulation; creation of action potentials through sympathetic nerve fibers, in the peripheral nerves being stimulated; creation of action potentials in peripheral nerves being stimulated; activation of the sodium pump, in the nerves being stimulated; production of ACTH; production of dynorphins, enkephalins or beta-endorphins; creation of action potentials in sympathetic fibers within the peripheral nerves being stimulated, which enter the sympathetic ganglia directly; analgesia causing a reduction in the production of substance P; and/or the production of circulation altering neuropeptides such as vasoactive intestinal polypeptide(VIP) and calcitonin gene-related peptide (CGRP).
There is considerable peer review medical journal literature to support these hypotheses.
Kaada found that distant, low frequency TNS (2 Hz) improved microcirculation in ischemic limbs of patients with Raynaud's phenomenon and diabetic neuropathy and to accelerate healing of chronic skin ulcerations. He also found that skin temperature increased 1.8 to 2.8 degrees centigrade and persisted for several hours after treatment. Plasma VIP was increased 60% following stimulation.
Kaada felt that the improved microcirculation of the skin was most likely caused by a sympatho-inhibition effectuated through a central serotoninergic link, since the response was blocked by the serotonin blocker cyproheptadine. In addition, the vasodilation was proportional to the increase in plasma VIP.
He stated that the mechanism of the relief of pain from wounds and ulcers was probably due to the vasodilation and endorphins, as well as, the release of ACTH and adrenocortical hormones caused by the electrical stimulation. Naloxone did not alter the vasodilatory effect or pain relief. He felt that this was due to an increase in VIP, which evidently affects the arterio-venous anastomoses. (8)(9)(10)
Kaada felt that the improved microcirculation resulting from the electrical stimulation was probably due to:
- Sympatho-inhibition. It has been shown that this reflex inhibition is relayed over the depressor area of the medulla oblongata. Experiments have shown that the vasodilatory response can be antagonized by the administration of a central serotonin blocker, suggesting the involvement of a central serotonergic link.
- Release of a vasodilatory substance, which was probably vasoactive intestinal polypeptide.
- ACTH-release. In addition to improved microcirculation, tissue repair may possibly also be accelerated by an endogenous ACTH-release; which has been shown to occur in response to low-frequency peripheral stimulation. (6)
VIP is not a blood-borne hormone. An increase in plasma VIP in the systemic circulation represents an overflow from synapses, caused either by an increased release or by a reduced degradation of the neuromodulator. An unexpected finding in these studies was that the resting values of plasma VIP were significantly (about 30%) lower in Raynaud and sclerodermic patients than in normal subjects. It has previously been suggested that one explanation could be that this lower plasma VIP concentration represents a defect in the VIP system in these patients and that it is a pathogenetic factor in the disease. (7)
Said stated that VIP stimulates the release of multiple chemicals, including serotonin. It has been shown that VIP enhances the binding of serotonin to its receptors in rat hippocampus. VIP binding sites have been identified in the hypothalamus, cerebral cortex, and pineal. Intracerebroventricular administration of VIP has a hypnogenic effect in rats and cats rendered partially insomniac. VIP stimulates cyclic AMP production, which in turn increases the production of melatonin. VIP is a dominant factor in increasing the availability of glucose from glycogen, promotes glucose utilization, and inhibits platelet aggregation. (16)
Groneberg et al stated that vasoactive intestinal polypeptide (VIP) is one of the most abundant, biologically active peptides found in the human lung. VIP is a likely neurotransmitter or neuromodulator of the inhibitory non-adrenergic non-cholinergic airway nervous system and influences many aspects of pulmonary biology. In human airways VIP-immunoreactive nerve fibers are present in the tracheobronchial airway smooth muscle layer, the walls of pulmonary and bronchial vessels and around submucosal glands. Next to its prominent bronchodilatory effects, VIP potently relaxes pulmonary vessels. The precise role of VIP in the pathogenesis of asthma is still uncertain. Although a therapy using the strong bronchodilatory effects of VIP would offer potential benefits, the rapid inactivation of the peptide by airway peptidases has prevented effective VIP-based drugs so far and non-peptide VIP-agonists did not reach clinical use. (3)
Wagner et al stated that vasoactive intestinal polypeptide (VIP) is known as an important regulator of airway function. It has been suggested that VIP is involved in the pathogenesis of asthma due to its relaxant effects on smooth muscles. They studied the effects of the peptides of the VIP family on airway mucus secretion. The peptides VIP, PHI, PACAP-27, PACAP-38, GLP-I, exendin-4, helodermin, helospectin I, and helospectin II were investigated using isolated rat trachea. The rank order of potency was PACAP-27 > VIP > helospectin II > PHI > exendin-4 = helodermin = helospectin I = PACAP-38. These data show that the peptides of the VIP family stimulate airway mucus secretion differently. (17)
Ollerenshaw et al stated that vasoactive intestinal polypeptide (VIP) is a neuropeptide present in the nerve fibers of normal lungs, where it acts to relax bronchial smooth muscle. They examined lung tissue obtained at autopsy or lobectomy from five patients with asthma and nine without asthma to determine its presence or absence in the lungs of patients with asthma. The avidin-biotin-peroxidase complex technique was used to stain tissue for immunoreactivity to VIP. At least 80 tissue sections from each patient were examined microscopically; the airway diameter ranged from 100 microns to 1.2 cm. Immunoreactive VIP was seen within nerves in more than 92 percent of the sections from the lungs of patients without asthma. No VIP was seen in any of 468 sections they could evaluate that were obtained from the lungs of patients with asthma. As a control for the nonspecific destruction of neuropeptides, immunostaining for substance P was also carried out. Abundant amounts of this neuropeptide were seen within nerves in tissue from the lungs of all patients. They concluded that in patients with asthma there is a loss of VIP from the pulmonary nerve fibers that may diminish neurogenically mediated bronchodilation. (14)
Yu et al stated that the characteristic feature of asthma is bronchial hyperresponsiveness (BHR), due predominately to inflammation of airways. Pathologically, there are inflammatory infiltration, epithelial sloughing and mucosal edema in the bronchi. They studied the relationship between BHR and airway inflammation. 57 cases of asthma and 22 normal subjects were tested with bronchial reactivity examination and P-selectin, substance P (SP) and vasoactive intestinal peptide (VIP) in plasma. They found that the bronchial reactivity to inhaled methacholine was positive in 53 of the 57 asthmatic patients (92.98%), while the remaining four were negative (7.02%). Twenty-two normal subjects were all negative with the test of bronchial reactivity. The levels of P-selectin and SP in asthmatics with corticosteroids treatment (n = 27) were higher than those in the control group (P < 0.05), but lower than those in asthmatics treated with aminophylline and salbutamol sulfate (n = 30), (P < 0.01). The concentration of VIP in asthmatics with corticosteroids treatment was significantly higher than that of asthmatics with out corticosteroids treatment (P < 0.01) but lower than that in the control group (P < 0.01). There was positive relationship between bronchial reactivity and P-selectin (r = 0.328, P < 0.05), as well as SP (r = 0.529, P < 0.01) in asthmatics, but negative relationship between bronchial reactivity and VIP (r = -0.419, P < 0.05). Their conclusion was that an increase of P-selectin and SP and decrease of VIP can induce BHR, corticosteroids can reduce levels of P-selectin, SP and enhance the level of VIP. Therefore it can improve the reactivity of airway and relieve symptoms. (18)
Liu et al stated that vasoactive intestinal peptide (VIP), which is localized in normal human lung, may play an important role in regulating bronchial tone, pulmonary blood flow and mucus secretion. The level of plasma VIP and bronchial responsiveness were studied in patients with asthma, chronic bronchitis and the healthy subjects. The results showed that the level of plasma VIP in asthmatic patients during acute attack and symptom-free period was significantly lower than that in the patients with bronchitis and the healthy subjects and it is negatively correlated with the bronchial hyperresponsiveness. They concluded that both asthmatic attack and bronchial tone are related with the decrease of VIP. (12)
Liu et al stated that non-adrenergic non-cholinergic (NANC) nerves are the third nervous system in the lung. There are increasing evidences that the main transmitters of NANC inhibitory (NANC-i) nerves and NANC excitatory (NANC-e) nerves are vasoactive intestinal peptide (VIP) and substance P (SP) respectively. They measured the levels of plasma VIP, substance P, and bronchial responsiveness in the patients with asthma, chronic bronchitis, and healthy subjects. The results showed that VIP level was decreased and negatively correlated with airway resistance, whereas SP level was increased and positively correlated with bronchial hyperresponsiveness (BHR) in asthma. They concluded that overexcitation of NANC-e nerves and deficiency of NANC-i nerves is closely related with asthma attack and BHR. (13)
Paul et al state that vasoactive intestinal peptide (VIP) is a potent relaxant of the airway smooth muscle. In their study, VIP-binding autoantibodies were observed in the plasma of 18% asthma patients and 16% healthy subjects. Immunoprecipitation studies and chromatography on DEAE-cellulose and immobilized protein G indicated that the plasma VIP-binding activity was largely due to IgG antibodies. Saturation analysis of VIP binding by the plasmas suggested the presence of one or two classes of autoantibodies, distinguished by their apparent equilibrium affinity constants (Ka). The autoantibodies from asthma patients exhibited a larger VIP-binding affinity compared to those from healthy subjects (Ka 7.8 x 10(9) M-1 and 0.13 x 10(9) M-1, respectively; P less than 0.005). The antibodies were specific for VIP, judged by their poor reaction with peptides bearing partial sequence homology with VIP (peptide histidine isoleucine, growth hormone releasing factor and secretin).
Ig G? prepared from the plasma of an antibody-positive asthma patient inhibited the saturable binding of 125I-VIP by receptors in guinea pig lung membranes (by 39-59%; P less than 0.001). These observations are consistent with a role for the VIP autoantibodies in the airway hyperresponsiveness of asthma. (15)
Du et al studied the changes of autonomic nervous function in the young adult with asthma through the heart rate variability (HRV). Twenty-four hours Holter monitored and heart rate variability analysed. They found that the HF and pNN50 that showed the vagal tone in asthma subjects increased as compared with the normal group, while the LF and SDANN that mainly showed the sympathetic tone decreased (P < 0.01). These values were remarkable in the severe asthma group (P < 0.01). They concluded that even in normal conditions, when patients are free of asthmatic attack; autonomic nervous function of asthmatics differs from that of normal young adults. (1)
Furii et al stated that bronchial asthma is associated with abnormal autonomic nervous function in childhood. Exercise is one of the most common precipitating factors of acute asthmatic crises although the exact mechanism of autonomic regulation in asthmatic children after exercise is unclear. Pulmonary function tests and heart rate variability spectral analysis were performed in 15 asthmatic children and 7 control children (age 6 to 15 years) during and after an exercise challenge. The maximum % fall of forced expiratory volume in 1 second (FEV1) was significantly greater (P < .01) in asthmatic subjects (9.1 +/- 5.1%) than in normal control subjects (1.0 +/- 2.5%). The high frequency band (HF) amplitude, an index of cardiac vagal tone, 5 minutes after exercise was significantly higher (P < .05) in the asthmatic subjects (14.4 +/- 7.9 msec) than in control subjects (5.9 +/- 2.6 msec). Furthermore, the difference in the HF amplitude between the control group and the exercise-induced asthma group was significant both 5 minutes (P < .01) and 10 minutes (P < .05) after challenge. There was a significant correlation (P = .565, P = .0165) between HF amplitude 5 minutes after exercise and the magnitude of the decrease in FEV1. On the other hand, no significant difference was observed in the low frequency band amplitude between the controls and the asthmatic subjects. The ratio of low frequency to high frequency power, which is suggested to correlate with cardiac sympathetic activity, did not differ between the two groups. They concluded that these findings suggest that autonomic nervous activities, particularly vagal response after suggest that autonomic nervous activities, particularly vagal response after exercise, in asthmatic children is different from that in control children. (2)
Kazuma et al stated that the autonomic circadian rhythm plays an important role in asthma. In recent years it has become possible to evaluate autonomic nervous function (ANF) using analysis of heart rate variability (HRV). Evaluation of the HRV was carried out using time-domain and frequency-domain analyses. The ANF of asthma subjects was decreased in comparison to the normal group. The severity of asthma had a significant effect on the %RR50 (the proportion of cycles during which the difference is > 50 ms), the SD (standard deviation; mean of standard deviation of all normal RR intervals for all 5-minute periods), the low-frequency (LF) band (0.04 to 0.15 Hz), and the high-frequency (HF) band (0.15 to 0.4 Hz) (%RR50: F = 4.31, p = 0.01; SD: F = 3.48, p = 0.03; LF: F = 3.67, p = 0.02; HF: F = 3.41, p = 0.03). These values were lowest in the severe asthma group. With regard to the therapy grouping, the index that exhibited a significant difference was the NNA (mean of normal-to-normal RR intervals over 24h) (F = 4.43, p = 0.01). In conclusion, even in the normal condition in which the patient is free of an asthma attack, the ANF of asthma sufferers differs from that of normal children. It is possible that the different ANF of asthma sufferers is related to the severity of the asthma. (11)
Jartti et al studied the features of cardiovascular and respiratory autonomic nervous regulation in asthmatic and control children. Cardiorespiratory reactivity was studied by continuous and non-invasive recording of the electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions and during a deep breathing test in 19 children with bronchial asthma and 10 healthy control children (age 8-11 years). Nine asthmatic children without beta2-agonist medication had a lower respiratory rate and larger high frequency (HF) variability of SAP than the controls, and 10 asthmatic children with beta2-agonist medication had greater low-frequency (LF) variability of SAP and LF/HF ratio of R-R intervals, but their respiratory rate did not differ from the controls. No intergroup differences were found in the postural change of variables. Stable bronchial asthma appears to increase respiratory-induced alterations in systolic blood pressure in children. Beta2-agonist medication, on the other hand, increases sympathetic cardiovascular activity in children with asthma. (5)
ASTHMA REFERENCES
1 Du J, He J, Wang Y. "A study of heart rate variability in asthma." Zhonghua Jie He He Hu Xi Za Zhi 2001 Dec;24(12):744-5.
2 Fujii H, Fukutomi O, Inoue R, Shinoda S, Okammoto H, Teramoto T, Kondo N, Wada H, Saito K, Matsuoka T, Seishima M. "Autonomic regulation after exercise evidenced by spectral analysis of heart rate variability in asthmatic children." Ann Allergy Asthma Immunol 2000 Sep;85(3):233-7.
3 Groneberg DA, Springer J, Fischer A. "Vasoactive intestinal polypeptide as mediator of asthma." Pulm Pharmacol Ther 2001;14(5):391-401.
4 Guido E. "Effects of Sympathetic Therapy on Chronic Pain in Peripheral Neuropathy Subjects". American Journal of Pain Management 2002 Jan; 12(1):31-34.
5 Jartti TT, Tahvanainen KU, Kaila TJ, Kuusela TA, Koivikko AS, Vanto TT, Valimaki IA. Cardiovascular autonomic regulation in asthmatic children evidenced by spectral analysis of heart rate and blood pressure variability. Scand J Clin Lab Invest 1996 Oct;56(6):545-54.
6 Kaada B "Promoted healing of chronic ulceration by transcutaneous nerve stimulation (TNS)." Vasa. 1983;12(3):262-9.
7 Kaada, B "Successful treatment of esophageal dysmotility and Raynaud's phenomenon in systemic sclerosis and achalasia by transcutaneous nerve stimulation. Increase in plasma VIP concentration." Scand J Gastroenterol. 1987 Nov;22(9):1137-46.
8 Kaada B "Systemic sclerosis: successful treatment of ulcerations, pain, Raynaud's phenomenon, calcinosis, and dysphagia by transcutaneous nerve stimulation. A case report." Acupunct Electrother Res. 1984;9(1):31-44.
9 Kaada B "Vasodilation induced by transcutaneous nerve stimulation in peripheral ischemia (Raynaud's phenomenon and diabetic polyneuropathy). Eur Heart J. 1982 Aug;3(4):303-14.
10 Kaada B, Lygren I "Lower plasma levels of some gastrointestinal peptides in Raynaud's disease. Influence of transcutaneous nerve stimulation." Gen Pharmacol.1985;16(2):153-6.
11 Kazuma N, Otsuka K, Matsuoka I, Murata M. "Heart rate variability during 24 hours in asthmatic children." Chronobiol Int 1997 Nov;14(6):597-606.
12 Liu A, Li PS, Zhang ZJ. "A clinical study on determination of plasma vasoactive intestinal peptide and the relationship between plasma vasoactive intestinal peptide and bronchial responsiveness in asthmatics." Zhonghua Nei Ke Za Zhi 1993 Mar;32(3):165-6.
13 Liu A, Li PS, Zhang ZJ. "A clinical study on the effect of non-adrenergic non-cholinergic nerves in asthma." Zhonghua Nei Ke Za Zhi 1993 Mar;32(4):223-5.
14 Ollerenshaw S, Jarvis D, Woolcock A, Sullivan C, Scheibner T. "Absence of immunoreactive vasoactive intestinal polypeptide in tissue from the lungs of patients with asthma." N Engl J Med 1989 May 11;320(19):1244-8.
15 Paul S, Said SI, Thompson AB, Volle DJ, Agrawal DK, Foda H, de la Rocha S. "Characterization of autoantibodies to vasoactive intestinal peptide in asthma." J Neuroimmunol 1989 Jul;23(2):133-42.
16 Said SI. "Vasoactive intestinal polypeptide (VIP): Current Status" Peptides. 1984 Mar-Apr;5(2):143-50. Review. "Vasoactive intestinal polypeptide: functional aspects." Br Med Bull. 1982 Sep;38(3):265-70. Review18 Fahrenkrug J, Emson PC.
17 Wagner U, Bredenbroker D, Storm B, Tackenberg B, Fehmann HC, von Wichert P. "Effects of VIP and related peptides on airway mucus secretion from isolated rat trachea." Peptides 1998;19(2):241-5
18 Yu H, Ren J, Wang F, et Al. "P-selectin and tachykinins in bronchial hyperresponsiveness of asthma." Zhonghua Nei Ke Za Zhi 1999 Apr;38(4):228-30.
