Saltrooms.co.il

Current reviews of allergy and clinical immunology
(Supported by a grant from Astra Pharmaceuticals, Westborough, Mass)
Series editor: Harold S. Nelson, MD
Alternative medicine for allergy and
asthma
Irwin Ziment, MD,a and Donald P. Tashkin, MDb Sylmar and Los Angeles, Calif
Orthodox medical approaches to asthma and allergic respira-
tory diseases are provided in guidelines developed by profes-
sional societies and national or state organizations that repre-
CAM: Complementary and alternative medicine sent organized medicine. Alternative therapies may include
such orthodox medical therapies as obsolescent formerly used
agents, unusual but accepted agents, and agents that are in
favor for orthodox therapy in other countries. However, the
current growth of complementary and alternative medicine is
based on the use of nonorthodox remedies that are becoming
increasingly popular with patients and that should be familiar
lous placebos,7 whereas others are adjuvants that may to physicians. Asthma and allergies are frequently treated with
work through important and acceptable mechanisms, such remedies by patients, either as part of self-therapy or on
such as by alleviating anxiety. Similar remarks may the advice of a complementary and alternative medicine prac-
apply to nonorthodox diagnostic and therapeutic modali- titioner. The most popular alternative medical treatments are
ties used in the treatment of allegedly allergic disorders.
herbs (Western and Asiatic), acupuncture, various types of
Nevertheless, in spite of these reservations, there is a sur- body manipulation, psychologic therapies, homeopathy, and
prising amount of clinical and laboratory information unusual allergy therapies. There is little evidence in favor of
most of these unorthodox treatments, although they are very
that has been published in support of some of the alter- often reported on favorably by patients. The published evi-
native remedies for asthma and hayfever.5,8 In this review dence that might support some alternative medical practices is
particular emphasis will be given to the more scientific reviewed so as to help physicians select alternatives that could
literature on herbs, homeopathy, unusual drugs (includ- appropriately be integrated into orthodox practice. (J Allergy
Clin Immunol 2000;106:603-14.)
HISTORICAL HIGHLIGHTS
Key words: Asthma, alternative medicine, herbal therapy, homeo-
pathic remedies, acupuncture, marijuana, psychologic therapies
Some of the historical theories, techniques, and treat- Complementary and alternative medicine (CAM) has ments that have been used in the management of breathing become an increasingly appealing component of standard disorders and chest diseases have persisted over thousands medical care, with physicians accepting the need to inte- of years.9 The favored drugs for asthma that were used in grate CAM with orthodox allopathic practices.1,2 Asthma the second half of the twentieth century had their origins in is one of a number of common disorders for which there folk remedies discovered by our ancestors. Thus ephedrine is a varied literature in support of CAM therapies.3-5 was developed from ma huang, a favorite Chinese herbal However, the extreme variety of approaches that can be remedy in use for thousands of years. Ancient asthmatic successfully used indicates that the majority of unusual subjects may have breathed in the smoke of heated henbane therapies must work on the overall mind-body relation- leaves, which released anticholinergic drugs, as did the ship that is a factor in the control of asthma.6 Many of stramonium cigarettes that were introduced into Europe these unorthodox therapies are fraudulent or are ridicu- from India in the nineteenth century.9-11 Asia also providedthe herbal origin of theophylline, which is found in tealeaves. Interestingly, the related herbal product caffeine andits congeners in coffee offered a favorite asthma remedy From aOlive View-UCLA Medical Center, Sylmar; and bUCLA School of during the same century. Cromolyn was a derivative of the chromones found in Ammi visnaga, the source of the Received for publication May 1, 2000; revised June 2, 2000; accepted for ancient Middle Eastern bronchodilator khella. Even Reprint requests: Irwin Ziment, MD, Professor and Chief of Medicine, Olive steroids have a historical precedent, such as the use of pla- View-UCLA Medical Center, Department of Medicine 2B182, 14445 centas or pubescent boys’ urine in treating asthma, where- as in the first half of the nineteenth century, ground adre- nal glands were used. Some of these ancient sources of 1/1/109432
therapy are still made available today.
604 Ziment and Tashkin
TABLE I. Representative Chinese remedies for asthma
HERBAL THERAPIES
Bupleurum, cordyceps, ephedra (Ma huang), ginkgo, licorice, magnolia, pinellia, platycodon, polygonum, Traditional Chinese medicine (TCM) is the most inter- esting systematized alternative medical system available in the West, and it is largely based on the use of hundreds of unfamiliar herbs, many of which have been used for Ge Jie Anti-asthma Pill, Crocodile Bile Pill, Minor hundreds of years (Table I).15 The typical TCM herbal prescription may contain 10 to 16 herbs, and ma huang Saibuko-to, shoseiryu-to, moku-boi-to, sho-saiko-to, (ephedra) is usually the only one with proven pharmaco- logic benefit. However, Ginkgo biloba has been used as The majority of Chinese drugs are not of proven value; ephedra and cordy- an asthma remedy, although its clinical value appears to ceps appear to be the most effective of these agents.
be negligible. Nevertheless, ginkgo extracts have been *These are Japanese combination products, which may have antileukotriene shown to have platelet-activating factor–antagonist effects, as do a number of other traditional respiratoryherbs, such as coltsfoot, which is used as an antitussive.16 Herbal products and associated chemicals and animal Some TCM herbs, such as various Datura plants, have parts in great profusion have been used as folk remedies anticholinergic effects. Some (eg, Cordyceps sinensis, to treat cough, chest pain, wheeze, expectoration, rhinor- licorice, skullcap, and Perilla frutescens) have been rhea, dyspnea, and associated problems, such as fever, shown to have anti-inflammatory properties, and others malaise, and debility.12 These historical therapies can be may have nonspecific mucokinetic actions. Many of the numerous herbs used by Chinese practitioners for asthma 1. Inhalants. Inhaled remedies have varied from sacred and allergy have been carefully reviewed in a comprehen- incenses to cigarettes and from pungent chemicals to sive analysis by Bielory and Lupoli,17 but their clinical natural climates, such as sea air. Some, such as those value remains uncertain. However, individual prepara- derived from solanaceous plants containing anti- tions and combinations are readily obtained, and adven- cholinergic drugs, would have eventually been rec- turesome patients may be using them. Popular proprietary ognized to act as bronchodilators, whereas others products include Ge Jie (Fig 1) and Crocodile Bile Pill would have been used just to cause an irritant expec- (Fig 2); these and others, such as Minor Blue Dragon Mixture, are based on ma huang and also contain such 2. Magical potions. Witch doctors, shamans, priests, herbs as goldenthread, peony, orange peel, cinnamon, gin- and protophysicians relied on various forms of mag- ger, licorice, pinellia, and schizandra, along with such sig- ical healing that could be delivered through the medi- nature constituents as gecko tails and cinnabar (mercuric um of inspired concoctions of medicaments. These sulfide). Other combination products include Kan-Lin varied from the toxic, such as herbal emetics, to the and Wen Yang, which also contain herbs such as aconite, disgusting, such as foul-tasting mixtures. Each might rehmannia, yam, epimedium, psoralae, dodder, astra- have been thought to work by driving out evil spirits, galus, poria, angelica, bupleurum, atractylodes, codonop- and in fact, they could help by inducing expectora- sis, ginger, date, and scute. Similar herbal formulas are tion. Other magical remedies varied from the sym- available for allergic rhinitis; examples include Turtle bolic fox lungs or flowers that look like lungs to Shell, Cistanche combination, and Jade Screen powder.15 impressive expensive products from distant sources, Unfortunately, exotic drug preparations are likely to be such as imported guaiac wood from America, which unreliable in the amount of active drug content, and they led to the development of guaiafenesin. It is of inter- may be contaminated with active drugs, such as cortico- est that magical asthma remedies are still in use steroids, or with hazardous agents, such as lead.
today, such as swallowing new-born live mice, eating Kanpo is the Japanese traditional medical system that is fried bat, or consuming gecko tails or earthworms.13 related to TCM. A number of well-known herbal combina- 3. Pharmacologic drugs. Most of the drugs in persistent tions are widely used by Japanese practitioners for asthma use during the last century were derived from natur- and hayfever.18 Representative ones, such as saibuko-to and al products, particularly herbs and chemicals, such as sho-saiko-to, contain such constituents as ephedra, licorice, salts. Careful observation by astute healers or physi- asarum, schisandra, peony, poria, scute, Chinese date, cians established the objective value of many of bupleurum, perilla, pinellia, ginseng, ginger, and magnolia.
these, such as ma huang for asthma, cough, and rhi- Syo-seiryo-to has been shown to be effective in nasal aller- gy. Studies suggest that some of these Kanpo combinations Other historical approaches of relevance include the have useful properties, including the ability to suppress elimination of dusts and animal products (eg, feathers), cli- lipoxygenase and cyclooxygenase activity, and they may mate changes, regulation of daily activities and sleep, and affect corticosteroid metabolism.19 However, it should also other adjustments that are classified as holistic. Mai- be recognized that these agents can be toxic, and thus sho- monides, in the twelfth century, gained fame for recom- saiko-to use could be a cause of acute pneumonitis.20 mending such life-regulation approaches for asthma, and his In Indonesia a similar herbal system is used, but the concept of using spicy chicken soup persists to this day.14 Jamu pharmacopeia has not been adequately evaluated.
Ziment and Tashkin 605
FIG 1. Ge Jie Anti-asthma Pill contains apricot kernels, cinnabar, coptidis, ephedra, gecko lizard tail, licorice,
ophiopogon, and scutellaria.
FIG 2. Crocodile Bile Pill for Asthma contains adenophora, asparagus, aster, calcium sulfate, crocodile bile,
ephedra, gypsum, lily, ophiopogon, orange peel, peony, perilla, peudanum, platycodon, scutellaria, and tri-
cosanthese.
Other systems of drug therapy exist in many Southeast boswellic acid, have demonstrated that it can inhibit 5- Asian countries, but no additional remedies of value seem to have emerged from this vast repertoire of histor- European herbs are relatively disappointing, and no major drugs for asthma or allergies have been derived Indian systems of traditional medicine are well sys- from them. Most of the respiratory herbs indigenous to tematized but are largely unrecognized in the West.
Europe are nonspecific mucokinetics; in this respect Ayurveda is gaining greater visibility; related systems, mustard and horseradish are possibly the most effec- such as Unani-Tibb, Siddha, Tibetan and the Indosyunic tive.25 Of course, European studies helped establish the system of Pakistan, are likely to remain obscure.21,22 value of imported foreign herbal remedies, including Some Ayurvedic drugs of interest for consideration in atropinic cigarettes (Fig 3) and theophylline. A curious asthma include Datura plants (the historical source of absence has been that of significant herbal antihistaminic atropine); Tylophora asthmatica, which is used for asth- or anti-inflammatory drugs other than cromolyn. A Ger- ma; and the malabar nut, from which the European man herbal product for sinusitis and bronchitis (that is mucokinetic agent bromhexine was derived. Coleus now available in the US) contains elderberry, gentian, forskohlii is a plant from which an interesting β-sympa- primrose, sorrel, and vervain, and careful laboratory and thomimetic drug has been obtained; forskolin (colforsin) clinical studies show that this combination may be effec- enters cells and directly stimulates the production of tive, having antiviral, anti-inflammatory, and mucokinet- cyclic 3,5-adenosine monophosphate, but its clinical ic effects.26 Other German remedies for colds and coughs value in asthma has not been adequately established.23 include linden, ivy, soapbark, chamomile, birch, willow, Other agents used for asthma and coughs include spices, peppermint, rose hips, mallow, pine, myrtol, thyme, and frankincense, jaggery, Indian gooseberry, costus, and meadowsweet; these are often used in teas, but their myrobalm. Studies on frankincense, which contains 606 Ziment and Tashkin
slippery elm. It would be expected that honey, candies, orother nonspecific throat drops may be just as effective asthe mucilaginous contents of these phytomedicines.
In contrast to herbs, it is possible that some foods (onion, garlic, pungent spices, antioxidants, omega-3 fatty acids,and essential oils from citrus fruits) and vitamins are ofphysiologic value in helping improve natural body defens-es.29-31 There is some evidence, which is not uniform, thatthe addition of such food derivatives to the diet of patientswith chronic airway hyperreactivity may be beneficial.
Similarly, epidemiologic studies suggest that increasingmagnesium intake and decreasing salt and sugar consump-tion can help stabilize brittle asthma.32 In contrast, foodallergy is only an occasional cause of asthma.33 It can be concluded that herbal remedies offer a melange of nonspecific mucokinetics and placebos, withoccasional bronchodilator and anti-inflammatory reme-dies being discernible. However, the best of these ancientremedies, ma huang, is grossly inferior to orthodoxdrugs, in terms of both prime effects and side effects.
Thus herbs offer an alternative for only milder forms ofasthma or hayfever. Representative herbs are listed inTable II.
HOMEOPATHIC REMEDIES
The enthusiasm of many patients and some physicians for homeopathic treatment in asthma illustrates that com-pletely opposite approaches may be equally effective.
Thus Chinese herbal medicines may contain 10 or more FIG 3. Lancelot Cigarettes for Asthma contained stramonium.
components, which are boiled in water and used as a Similar cigarettes were marketed that contained belladonna.
soup. In contrast, classical homeopathy uses single herbs Added to these were other plant materials, such as tobacco, mar- diluted to the point that the final prescribed solution may ijuana, coltsfoot, mullein, hyssop, and cubeb. Some contained be totally free of any physical remnants of the original potassium nitrate, arsenic, or other chemicals.
drug. In each of these situations, there is an assumptionthat some essential quality of the administered cureserves to enhance the body’s ability to heal itself.
American herbal remedies of the past came mainly Traditional homeopathy uses unusual drugs, such as from Central and South America; ipecacuanha, pepper, bryony, sabadilla, spikenard, and burnt sponge, for asthma and guaiac are the best known. However, most South and hayfever.34,35 However, some formerly popular allo- American phytomedicines in use today for respiratory pathic drugs are also used, including stramonium, lobelia, disease are of dubious benefit (eg, lettuce, oregano, okra, onion, honey, nettle, and ipecacuanha. A more recent form and copaiba).28 Traditional North American herbal of homeopathy, termed isopathy, uses dilutions of aller- drugs, such as lobelia, yerba santa, senega, and creosote, gens or drugs that provoke bronchospasm. This variation are largely obsolescent, whereas emerging respiratory of homeopathic therapy has been the source of most of the drugs, such as echinacea, goldenseal, and sundew, are not clinical trials in asthma and hayfever.34 Finally, homeo- indicated for asthma or hayfever. However, meta-analy- pathic treatment can be self-selected, with patients using ses suggest that echinacea can help prevent and alleviate over-the-counter remedies, such as the popular isopathic common colds. It is of interest that some promoters of preparation Oscillococcinum for colds; this product is a echinacea claim that its immunostimulating effect should diluted autolysate of the heart and liver of a duck. Because be a contraindication to its use in asthma.
classical homeopathy uses very dilute solutions of drugs Universally popular respiratory remedies include that cause the same symptoms that are to be treated, it is eucalyptus, menthol, anise, fennel, tolu balsam, and cam- not surprising that onion is a treatment for rhinitis. Theo- phor; some of these are incorporated in products such as retically, a very dilute solution of a β-blocker could be Vicks VapoRub and Tiger Balm.24 These aromatic agents, when inhaled as vapors, can soothe the inflamed When a patient seeks traditional homeopathy, he or she nasal mucosa and seem to benefit the tracheobronchial will be carefully evaluated by the therapist with respect to tree. Other soothing remedies of the throat include men- symptoms and aspects of daily living; the patient’s per- thol, marshmallow, Iceland moss, mullein, plantain, and sonality type is also given consideration.36 The most suit- Ziment and Tashkin 607
TABLE II. Representative Western herbs for asthma
Possible expectorant effect*
Possible immune effect*
Possible bronchodilator effect
GoldensealGuaiacolHorehoundHorseradishMarshmallowMulleinMustardPeppers (eg, capsicums and cubeb)SarsparillaSnakerootSkunk cabbageSquillStoraxSundewTerpeneThyme *None of these agents is of proven value for asthma or allergic respiratory diseases.
able homeopathic preparation is then selected from a spe- are certainly worthy of some respect in that they suggest cial therapeutic guidebook or repertory. Thus the person- that homeopathy is more than simply placebo therapy.40 al attention given to the patient may be a potent factor The existence of favorable results for asthma and leading to a therapeutic response. This explanation does hayfever in double-blind, placebo-controlled studies of not apply to the use of off-the-shelf remedies, yet several homeopathic remedies baffles and disturbs orthodox studies of such products have shown a benefit over place- physicians, but if one wishes to reject those peer- bo therapy in the treatment of asthma and allergic rhinitis.
reviewed publications that show favorable outcomes for Moreover, a famous study showed that sensitized homeopathy, one should be equally skeptical of favorable basophils could be degranulated by a solution of anti-IgE findings in double-blind, placebo-controlled studies on antibodies diluted to 10–120; such a solution contains not even one molecule of anti-IgE, although it may “retain the The problem with homeopathic medications is that their beneficial effects in asthma and allergy may depend Reilly et al38 have studied homeopathic treatments in on nonmaterial mechanisms that require an expanded hayfever and in asthma. One hundred and fifty-eight dimension in thinking about the therapeutic actions of patients with seasonal rhinitis were given either a home- medications. Thus it is worth reflecting on the early con- opathic remedy or a placebo twice a day for 2 weeks and cepts of Hahnemann, who formulated the practice of followed up 2 weeks later.38 Fifty-six patients receiving homeopathy. He believed that treating an inner disease the remedy were suitable for evaluation, as were 52 would initially drive it outwards, giving the example that receiving placebo. The responses were judged by using a when asthma improves, eczema may appear. Further- visual analogue scale, and this showed a significantly more, homeopathic theories provide a link between the greater response to the homeopathic therapy; a corre- therapeutic achievements of psychoanalysis on the one sponding reduction in the need for antihistamines was hand and trace minerals and hyposensitization therapy on also seen in these patients. The homeopathic preparation the other. It is not surprising that attempts are made to of mixed grass pollens was diluted to 1 in 10-6, and thus explain homeopathy’s therapeutic successes with exotic none of the active material existed in the remedy. A sim- theories on the basis of electromagnetism, nuclear mag- ilar study was carried out on asthma patients.39 Thirteen netic resonance, energy fields, and quantum physics. Of such patients received the allergen remedy diluted to 1 in course, one could use similar rationales to explain the 1060, and 15 received placebo. The actively treated group actions of pure placebos.39,42,43 Because placebos can showed significant improvement on the visual analogue exert significant therapeutic effects, there is still a need to scale, as well as in forced vital capacity and FEV1.
explore all possible mechanisms by which any therapy Although the results may not be totally convincing, they may bring about an inexplicable benefit.
608 Ziment and Tashkin
It must be concluded that homeopathy today is a very treating asthma with yoga breathing exercises and pos- variable alternative practice, with patients using self- tures,33,46,47 while Chinese qi gong practices48 can be of therapy at one extreme or relying on knowledgeable, benefit. Panic control and relief of anxiety are probably dedicated, careful homeopathic practitioners at the other of importance, and cognitive behavioral therapy can be extreme. Because patients may be equally satisfied by either approach, it is probable that most improvementsare explicable by the placebo effect. However, the intel- PSYCHOLOGIC THERAPIES
lectual challenge remains because for many years evi-dence has been published that would suggest a true ben- Religious experiences have a long history of value in efit may be attributed to homeopathy.44 One major the treatment of disease. Prayer, miraculous curing, faith criticism of quality homeopathic studies that show favor- healing, therapeutic touch, cult behavior, and shamanism able results is that the techniques that are used differ can still benefit those who are believers, although extreme from those used in everyday practices, and thus any find- approaches verge into exploitative or fraudulent manipu- ings of benefit from such studies cannot be used as an lation of a patient’s gullibility. Mesmerism, hypnotism, endorsement for current clinical practices in homeopathy biofeedback, and related practices can help improve auto- nomic imbalance in diseases such as asthma.33,50 Tran-scendental meditation can reduce the wasted energy of OSTEOPATHY AND CHIROPRACTIC
breathing and can decrease oxygen consumption. Thustraining patients to relax; to breathe; to sing, chant, or lis- In the nineteenth century, osteopathy and chiropractic ten to music; to exercise more economically; and to cough were born in the United States, and they are currently more effectively may result in measurable improvements.
accepted as effective health disciplines. These manipula- Positive imagery, in which a patient conjures up imagi- tive arts can be compared with TCM. Classical practi- nary scenes or feelings of improved body function, also tioners profess that by resolving the imbalance of energy leads to measurable benefit. Similarly, verbalizing or even flow in the body (as is supposed to occur particularly writing about stress factors can result in benefits in asth- with acupuncture), the body’s ability to heal itself is ma.51 Rehabilitation programs for patients with severe enhanced. Osteopaths often practice orthodox medicine airway disease emphasize comparable techniques and can and may incorporate manipulative therapy as adjuncts to also be of benefit by introducing socialization, motiva- routine drug prescriptions. In contrast, chiropracters do tion, compliance, anxiety control, and relaxation practices not prescribe drugs and may incorporate herbs, vitamins, (perhaps with the help of music)52 into the patient’s daily and other therapies along with manipulation.
life. Optimization of diet and weight, daily exercise, and The various techniques of osteopathy—such as infra- removal of bad habits (including smoking) may also be spinatus muscle injection with local anesthetic, a steroid, achieved with such programs. However, some patients or both, or thoracic pumping and lymphatic massage, require more radical experiences, such as a visit to a along with spinal and joint adjustments—may make shrine or a guru, or they need to make a pilgrimage or patients feel better, but they have not been proved to be of make a major commitment to a religious group. Such significant specific benefit for asthma or respiratory aller- experiences may be expected to increase patients’ toler- gies. Recently, a study on chiropractic manipulation in ance to disease and to help them control unfavorable psy- children with asthma suggested that genuine techniques chologic reactions that might contribute to the escalation were no more effective than sham techniques. Both of the symptomatic reactions that result from exposure to appeared to have an equal and measurable outcome, sug- stress. However, some fashionable techniques, such as gesting a placebo and Hawthorne effect attributable to the therapeutic touch, may not prove their value when sub- added attention that the patient receives during the course jected to scientific study.53 Many of the popular alterna- tive therapies are listed in Table III.
Numerous other body manipulation techniques are advocated by CAM practitioners for a large variety of ACUPUNCTURE IN ASTHMA
disorders, including asthma.1,6 Some of the better knownones include reflexology, shiatsu, Reiki, various types of At present, acupuncture is one of the most popular bodywork exercises and massage, breathing exercises, alternative therapies for asthma in the United States, and yoga exercises, qi gong exercises, spa therapy, and health with the help of competent practitioners, it is readily club activities. All may improve the general perception of available in major population centers. Acupuncture health, and although there is no evidence of specific ben- involves the insertion of thin needles into the skin at efit, such treatments may be valuable adjuncts to ortho- specified locations to regulate the flow of energy (Chi) dox medical treatment and can be used as part of inte- that is believed to control psychophysical function.54 grative and holistic management. The patient who makes Once Chi is accessed at points on the meridians along a dedicated commitment to these therapeutic practices which energy flows, it can be regulated by gently manip- invests considerable faith in the techniques, and this ele- ulating the needle at different frequencies or by other ment will assure a placebo response of significant means, such as electrical stimulation or burning the herb degree. However, there is some evidence in support of Artemisia vulgaris on the end of the needle (moxibus- Ziment and Tashkin 609
TABLE III. Major CAM choices
Western: herbs, phytochemicals, botanical; Chinese: CTM, Kanpo, Jamu; Indian: Ayurveda, Unani, Siddha Elimination: additives, processed foods, salt, allergens (eg, spices, milk, nuts, eggs), toxins, yeast products; addition: magnesium, selenium, omega-3 fatty acids, antioxidants (eg, vitamins), coffee, teas, pungent spices Classical, modified, isopathy, pseudohomeopathy Manipulation, lymphatic massage, exercise Correction of subluxations, massage, postural adjustments, vitamins, diet Breathing technique, yoga, Chinese (eg, qi gong, tai chi) Climate, spas, air purifiers, aromatherapy Numerous types (eg, shiatsu, reflexology) Unusual vaccines or desensitization techniques, embryonic call derivatives, thymus stimulation Vagal, chest wall, lung and esophageal procedures; thymectomy, splenectomy, adenoidectomy Fruit and vegetable diets, elimination diets, hydrotherapy, enemas, wheatgrass juice Classical, electroacupuncture, acupressure, moxibustion Magnesium preparations, heparin, local anesthetics, and a host of others TABLE IV. Results and quality of published placebo-controlled trials of acupuncture in asthma
Quality score
subjects
allocation
Type of asthma
(0-100)*
SA > saline > no treatment (positive) β-Agonist > RA > SA > no treatment *Quality of methodology scored by Kleijnen et al.68RA, Real acupuncture; SA, sham acupuncture.
tion). Acupuncture has the appeal offered by a nearly Many reports of the efficacy of acupuncture in asthma risk-free, relatively low-cost, nonpharmacologic form of published in the Chinese and Russian literature are based on uncontrolled observations and will not be further Although acupuncture has been used in China for commented on here. Only 13 controlled clinical trials of thousands of years for the treatment of asthma, only a real versus sham acupuncture in asthma have been pub- limited body of studies of the efficacy of acupuncture in lished, of which 6 were double-blind,55-60 and 7 were asthma have been carried out, mainly within the last 25 single-blind.61-67 Most of these have been reviewed by years, that use accepted Western scientific methods for Kleijnen et al.68 Two of the authors of the latter article clinical research. In the case of acupuncture, it is not pos- independently scored each of these studies for the scien- sible or practical to blind the acupuncturist, but the eval- tific quality of their methodology. The maximum possi- uators (nonacupuncturist clinician-investigator and tech- ble score was 100, and interrater agreement was good.
nical assessors) can and should be masked to the Features of these 13 studies are summarized in Table IV.
treatment condition (real vs sham acupuncture). Sham Unfortunately, most of the published clinical trials have acupuncture is usually accomplished by injecting methodologic shortcomings, including lack of double- acupuncture needles at false points (ie, locations not des- blinding, random allocation to treatment, or both; small ignated as true acupuncture points on the meridians in numbers of patients; and inadequate description of statis- any of the classical TCM texts). These sham points are tical analysis. Of the 6 double-blind studies, 4 were nega- generally selected 2 to 3 cm from the true point or in tive, whereas 6 of the 7 single-blind studies were positive.
All but one of the negative studies that were scored for 610 Ziment and Tashkin
methodologic quality had scores of greater than 50, claimed to benefit some patients, although rigorous proof whereas all but one of the positive studies had quality is lacking. It is probable that more consideration should scores of less than 50. Therefore on the basis of the pub- be given in treating patients with severe allergies to the lished literature, claims of the efficacy of acupuncture role of possible sensitizers, such as spices, fruits, food have not yet been convincingly supported by adequately preservatives, and coloring agents.71 The appropriate bal- designed clinical trials. Also, in all 3 studies that included ance between good, thorough, practical care and the a β-agonist as a positive comparator, the β-agonist was temptation to use alternative or even magical techniques unequivocally superior to real acupuncture.
may be tilted in favor of the latter when treating a highly Jobst54 has catalogued the side effects of acupuncture susceptible and demanding patient who favors exotic used in the treatment of asthma on the basis of reports from 16 published studies involving a total of 320 cases.
Side effects were reported in only 23 (7%) of the 320 UNUSUAL DRUGS
cases, and these have generally been mild (eg, vasovagalreactions, earache, and gastrointestinal symptoms), indi- Throughout history, numerous drugs and chemicals cating that acupuncture therapy for asthma is generally have been used in the treatment of asthma.9,12,25 safe. On the other hand, 5 cases of pneumothorax and Ephedrine and pseudoephedrine in ma huang have each one case of cardiac tamponade have been reported. In been used as pure drugs to treat asthma, but they are of addition, one case of hepatitis B caused by needle conta- limited value, and their effect diminishes because tachy- mination has been documented. It is therefore essential phylaxis develops. Many other sympathominetics are no that acupuncture be performed only by well-trained prac- longer mainstream or have entirely failed to enter the titioners and that only sterilized needles be used.
American market. The value of these was limited for var- Acupuncture is best reserved as an optional form of ther- ious reasons, including, in some cases, their toxicity.
apy that complements, rather than replaces, conventional These include methoxyphenamine and protokytol, which therapeutic modalities of proven effectiveness.
were used in the United States and broxaterol, carbuterol,clenbuterol, etafedrine, fenoterol, hexoprenaline, quin- ALLERGY THERAPIES
terenol, rimiterol, ritodrine, soterenol, trimetoquenol,and others that were used abroad. Phosphodiesterase Although it is reasonable to insist that patients avoid inhibitors that are not in use at this time include bam- obvious exacerbating factors in asthma and allergic dis- iphylline, dyphylline, proxiphylline, enprophylline, et- orders, alternative practitioners take elimination tech- ophylline, and quazodine. Anticholinergic drugs that niques to excess. Some of the diagnostic methods that are have been used in asthma include atropine, hyoscine used, such as evaluating the cytotoxic response to aller- (scopolamine), hyoscyamine, and glycopyrrolate; in gies, are frankly fraudulent.7,8 Others seem to incorpo- addition, asthma cigarettes containing stramonium (Fig rate folie à deux, where the patient and practitioners 3), and similar sources of atropinic drugs were formerly believe in extraordinary phenomena. Thus, in applied in favor. Before the modern drug era of the second half kinesiology, practitioners claim the ability to detect an of the twentieth century, asthma remedies included allergic response when a patient holds the offending food lobelia, potassium nitrate, amyl nitrate, pituitary extracts, in one hand and demonstrates a consequent weakness in khellin (from which cromolyn was derived), and a host of largely useless drugs, such as pyridine and turpentine Very few patients have hidden allergies, and elaborate derivatives. Asthma cigarettes often contained stramoni- efforts to restrict diets and detect any adverse response to um mixed with tobacco, mullein, coltsfoot, hyssop, hore- incremental reintroduction of foods may cause more hound, black tea leaves, marijuana, arsenic, and so on in harm than benefit. The adding of enzymes and special food products to improve digestion and reduce allergic More recently, methotrexate gained favor for steroid- manifestations is based solely on anecdotal reports.
dependent asthma, as had triacetyloleandomycin previ- Some practitioners try to desensitize patients by admin- ously. Neither agent nor other immunosuppressive drugs, istering injections of the patient’s own urine or blood.
such as cyclophosphamide or cyclosporin, are in favor Other extraordinary approaches include eye movement today.33 Magnesium sulfate given intravenously may be desensitization, reprocessing, and related psychological- of value in the management of a severe asthma attack, ly directed techniques.56 These treatments are accompa- and giving the drug by aerosol or incorporating it in the nied by pseudoscientific explanations to justify their use.
diet may help stabilize brittle asthma. However, the true However, occasionally an extraordinary technique may value of magnesium given as an aerosol preparation or in be of benefit, such as drinking wheatgrass to progres- the diet has not been established, and therefore it is an sively diminish allergy to wheat pollens or administering a rapid course of immunotherapy or giving intravenous Local anesthetics, such as lidocaine or mexiletine, IgG.70 Currently, it is in vogue to blame Candida albi- have been given by inhalation, with apparent benefit in cans as a cause of allergies and illness, such as hyperac- asthma. Heparin, which may have anti-inflammatory tivity, and to eliminate Candida albicans from the diet, or properties, has also been reported to be of value when to treat with antifungal agents. These practices are given topically into the lungs. Furosemide has for some Ziment and Tashkin 611
years been reported on favorably as an aerosol agent for ∆9-THC–induced airway smooth muscle relaxation asthma, but its clinical value and its mode of action are has not been found to be due to an adrenergic-mediated or muscarinic-antagonist effect77 or to direct effects in It is probable that at one time or another, almost every isolated human bronchiolar smooth muscle.78 Smoking class of drug has been described as being of benefit in marijuana is the simplest and most reliable method of asthma, although the supporters of agents such as aspirin, administration,79 but habitual inhalation of the toxic phenytoin, hydroxyzine, calcium channel blockers, pro- smoke components80 has been shown to cause extensive gesterone, and so on have failed to substantiate their airway injury and depressant effects on alveolar claims. Similarly, many drugs over the years that appeared macrophage function in cannabis smokers.81,82 The oral to be promising never got far beyond animal studies before route is not suitable because it is associated with variable falling into oblivion. However, some of these unusual and, at best, only modest bronchodilation, and unwanted drugs may still be used as alternative therapies in some psychotropic and cardiovascular effects. Therefore the countries. Antihistamines, including ketotifen, as a group possibility has been explored that inhalation of pure ∆9- have been disappointing in the treatment of asthma, THC as an aerosol might have therapeutic advantages.83 despite their value in treating extrapulmonary allergies.
A metered-dose inhaler (MDI) was specially formulatedwith ∆9-THC dissolved in 95% ethanol and chlorofluo- MARIJUANA
rocarbon as the propellant, generating 1 mg of ∆9-THCper actuation. Five to 20 actuations from this MDI pro- Preparations from the hemp plant, Cannabis sativa, duced bronchodilation in 11 healthy subjects of a magni- which contains the psychoactive principle ∆9-tetrahydro- tude less than that produced by smoked marijuana; more- cannabinol (∆9-THC), produce a pleasant intoxicating over, cough and chest discomfort were noted in a few effect. By the middle of the nineteenth century, marijua- healthy subjects. In 2 of 5 stable asthmatic subjects, 5 to na was prescribed as a bronchodilator. Its medicinal 10 mg of aerosolized ∆9-THC caused moderate-to-severe value declined by the early twentieth century with the bronchoconstriction, along with cough and chest discom- introduction of synthetic drugs.72 During the last two fort. The latter findings were presumably caused by a decades, potentially beneficial effects of smoked mari- local irritant effect of THC on the airways, leading to juana and oral and inhaled synthetic ∆9-THC in asthma reflex bronchospasm, which could have been related to have been investigated in human volunteers.
the dose of ∆9-THC administered (equivalent to the Two independent groups of investigators demonstrat- amount of ∆9-THC in a 500-mg cigarette of 2% marijua- ed a short-term bronchodilator response in healthy male na), the aerosol particle size, or both.83 volunteers to inhalation of the smoke of marijuana in In contrast, Williams et al84 noted significant bron- concentrations of 1.0% to 2.6% ∆9-THC73,74 that was not chodilation without any occurrences of bronchospasm in seen after inhalation of placebo. The bronchodilator 10 stable asthmatic subjects after administering a much response to smoked marijuana was of greater magnitude smaller dose of THC aerosol from an MDI (50 µg per than that observed after administration of a nebulized β- actuation). No associated side effects were noted on agonist. A dose-dependent bronchodilator response was mood, behavior, or the cardiovascular system. The onset also noted in healthy subjects to oral administration of 10 of bronchodilation was delayed compared with that of to 20 mg of synthetic ∆9-THC.74 Subsequently, 2% albuterol (100 µg), but the bronchodilator effect was smoked marijuana was observed to produce a similar comparable at 1 hour. In a subsequent study the same magnitude of bronchodilation in 10 stable asthmatic sub- group demonstrated a dose-response effect of 50 to 200 jects to that observed in normal subjects (approximately µg of THC in 5 asthmatic subjects, with achievement of 50% peak improvement in specific airway conductance a plateau of bronchodilation at 100 µg.85 No further [sGaw]), with a duration of action of 2 hours.75 Howev- investigations of the potentially therapeutic benefits of er, the peak magnitude of bronchodilation produced by aerosolized THC in asthma have been published to date.
15 mg of oral THC was slightly less in asthmatic than The possibility that some cannabinoids other than ∆9- normal subjects (20% vs 30% increase in sGaw, respec- THC might also exhibit bronchodilator effects has been tively).74,75 Moreover, the magnitude of bronchodilation investigated. Evaluation of ∆8-THC and cannabidiol failed achieved with the oral formulation was modest (mean to demonstrate any bronchodilation, except for a modest peak increase in sGaw of only ~20%-30%) compared effect of ∆8-THC in a 75-mg dose that also produced with an approximately 50% mean peak increase noted unwanted side effects.86 Similarly, no significant bron- with smoked marijuana, although the duration of bron- chodilation was observed with nabilone (2 mg), a synthet- chodilation was slightly longer after 15 mg of oral THC ic 9-keto cannabinoid that is chemically related to THC.87 (2-4 hours) than that of 2% smoked marijuana (2 The biologic effects of ∆9-THC are known to be medi- hours).74,75 In comparison with placebo, smoked mari- ated by two specific G protein–coupled receptors that are juana (500 mg of 2% ∆9-THC) also caused prompt cor- expressed on cells in the central nervous system (CB1 rection of the bronchospasm and associated hyperinfla- receptors) and on cells outside the central nervous sys- tion provoked by methacholine and, on a separate tem, including immune cells (CB2 receptors).88 Mam- occasion, by exercise in 8 subjects with clinically stable malian tissue produces two families of endogenous asthma and a history of exercise-induced asthma.76 cannabinoid ligands (anandamide and 2-arachidonyl 612 Ziment and Tashkin
glycerol) that bind to these receptors, yielding biologic their own accepted therapies, including second- and effects similar to those of plant-derived THC. Recent third-line prescription drugs and the use of diagnostic unpublished observations have disclosed CB1 receptors and therapeutic modalities, such as desensitization thera- on postganglionic parasympathetic nerve endings in py. The final outcome for physicians and patients is the bronchial tissue (D. Piomelli, personal communication, incorporation of a tailor-made regimen that matches the 1999) that have been linked in other tissues (eg, guinea physiologic and psychologic needs of individual patients.
pig ileum) to inhibition of release of acetylcholine. These The medical profession must serve as a resource of infor- observations suggest that THC (and related CB1 ago- mation and skills that can be incorporated in an integra- nists) may exert a local bronchodilator effect in the air- tive manner with the specific complementary regimen way through stimulation of CB1 receptors on efferent that resonates with the cultural and individualistic needs vagal nerve endings, leading to a parasympatholytic of each patient. Thus physicians should question each effect. It is hoped that novel ligands of high affinity and patient carefully about any alternative therapies that he or selectivity for the cannabinoid receptors may ultimately she may use, and an effort should be made to provide prove to be useful antiasthma medications. Until such thoughtful advice about the potential value or possible time, however, administration of THC in the smoked harm of incorporating such modalities into an integrated form should be discouraged because of the well-docu- therapeutic program on the basis of the orthodox man- mented pulmonary toxicity of smoked marijuana, includ- ing its potential to cause head and neck and other respi-ratory cancers.89,90 REFERENCES
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