Complementary, alternative, and integrative therapies for asthma

INTRODUCTION — The standard treatment of patients with asthma is based upon trigger avoidance combined with bronchodilator and anti-inflammatory therapy. Beta agonists, glucocorticoids, leukotriene modifiers, biologic agents, muscarinic antagonists (anticholinergics), and, to a lesser extent, methylxanthines all have a role in the conventional treatment of asthma. However, some patients do not achieve adequate control of their asthma with conventional therapy, experience adverse effects with conventional agents, or believe that complementary or alternative approaches may be better for them. For these patients, consideration may be given to the administration of nonstandard therapeutic regimens in order to ameliorate the acute or chronic manifestations of the disease.

Complementary, alternative, and integrative therapies for the treatment of acute and chronic asthma will be reviewed here. Standard and investigational treatment regimens for asthma are discussed separately. (See "An overview of asthma management" and "Acute exacerbations of asthma in adults: Home and office management" and "Investigational agents for asthma".)

Overall efficacy — Several nonpharmacologic approaches to asthma management have been proposed, including herbal medications, dietary interventions, behavioral therapies, acupuncture, massage, and speleotherapy. Evidence supporting the use of complementary and alternative medical approaches to improve asthma management is limited. A meta-analysis of 15 trials, many of which are discussed in the sections below, found insufficient evidence to recommend any of these interventions as a useful addition to standard asthma management [1]. A subsequent systematic review reached the same conclusion [2].

●Complementary-alternative medicine – The term "alternative medicine" was initially used to describe therapies used in place of conventional care. The term "complementary-alternative medicine (CAM)" is preferred because it recognizes the history and experience of traditional remedies in many countries and the potential role of "complementary-alternative medicine" techniques in disease management if they are demonstrated to be safe and effective.

Patients may turn to CAM therapists who offer them personal attention, hope, time, and therapies consistent with their values, world view, and culture.

●Integrative medicine – Integrative medicine refers to the integration of CAM therapies into mainstream medical practice based upon evidence of safety and effectiveness within the context of relationship-based care [3,4]. The emphasis is on achieving patient-centered care that draws from conventional and complementary medicine.

The large number of patients who seek out nonstandard therapies suggests that knowledge about the agents that patients may use and their potential risks and benefits would be helpful to asthma providers and enable them to discuss these choices with the patients [5,6]. A 10-step process on how to handle requests for alternative and complementary therapy has been described [7]. Steps include exploring the reasons for the patient’s interest in pursuing CAM therapies instead of conventional asthma therapy; assessing current asthma/health status and quality of life (symptom diary); reviewing and documenting medical evaluation and certainty of asthma diagnosis; discussing shared goals for disease and/or symptom control; sharing information about pros and cons of specific CAM agents that the patient is considering and expressing willingness to gather and share additional information; describing ways for patients to assess responses to CAM therapies; and documenting discussions, including potential adverse effects of particular CAM therapies.

We have found that increasing the frequency of office visits, even at weekly intervals, is a helpful strategy for patients who are considering unproven alternative techniques. The frequent office visits improve adherence to standard therapy and enable evaluation and optimization of inhaler technique. In addition, these visits provide an opportunity to establish a better provider-patient relationship with patients who are concerned about potential harms of standard therapy and skeptical of the benefits. During these visits, the provider can explore the patient's concerns about standard therapy and provide reassurance.

HOMEOPATHY — Homeopathy is a pre-scientific practice based on two tenets: "like cures like," meaning that a substance will cure a disease if it causes the symptoms of the disease, and "potentization," a belief that serial dilutions and "succussions" (shakings) render a "remedy" increasingly potent. The US Food and Drug Administration (FDA) has issued a warning to consumers not to rely on homeopathic products for asthma. Despite marketing claims that the products are "safe and effective," the products have not been evaluated by the FDA and should not be relied upon to treat asthma.

Homeopathic preparations ("remedies") generally begin with minerals, plants, or animal substances that are pulverized, mixed with a water-alcohol solution, and then potentized, usually well past the point at which any of the original substance remains. The resulting diluent is applied to a sucrose pill and allowed to dry. Homeopathy is discussed in greater detail separately. (See "Homeopathy".)

TRADITIONAL CHINESE MEDICINE — Traditional Chinese medicine (TCM) has been used to treat asthma in East Asia for centuries. A discussion regarding the use of Chinese herbal medicine to treat asthma is provided separately. (See "Chinese herbal medicine for the treatment of allergic diseases", section on 'Therapy for asthma' and "Overview of herbal medicine and dietary supplements".)

Herbal remedies carry the risk of incorrect or nonstandard selection of plants, preparation, and dosing, in addition to potential adulteration (eg, lead, ephedra) [2,8].

AYURVEDIC MEDICINE — Ayurvedic medicine is a medical tradition originating from India and derived from the teachings of ancient Hindu healers, which first appeared in text between 1500 and 1000 BC. Ayurvedic therapeutic interventions include yoga, meditation, breathing exercises, and herbal preparations. In its truest form, Ayurveda exists for the "promotion of health" rather than the treatment of specific disease states that have already begun to affect the body.

Some of the herbs used in Ayurvedic medicine are also used in traditional Chinese medicine [2,9,10]. Research is underway to identify the chemical components and properties of a number of these herbs [9,10].

One randomized trial in asthmatic subjects showed that the gum resin Boswellia serrata (a component of Ayurvedic remedies) significantly improved symptoms and increased forced expiratory volume in one second (FEV₁) 0.4L (95% CI 0.23-0.57) from baseline after a six-week course [11]. In a separate study, a traditional combination of Boswellia serrata, licorice root (Glycyrrhiza glabra), and tumeric root (Curcuma longa) was evaluated in 63 subjects with asthma [12]. After four weeks, the plasma leukotriene-C4 level decreased in the active therapy group, but not in the placebo group. A slight decrease in symptoms and rescue inhaler use was noted in the active therapy group, although the numbers were small. No significant change was noted in FEV₁.

Saiboku-to (TJ-96), a Japanese herbal therapy that similarly acts on the 5-lipoxygenase pathway, led to a significant decrease in asthma symptoms, blood and airway eosinophilia, and also hyperresponsiveness to methacholine when given to patients with asthma for four weeks [13]. However, the FEV₁ did not improve.

Other mechanisms may also contribute. As an example, glycyrrhizin has glucocorticoid-modifying activity [14].

DIETARY CHANGES AND SUPPLEMENTS — It is very difficult to study the impact of dietary changes upon the course of asthma and most studies show no effect [15-17].

●Antioxidants – Patients with severe asthma appear to have decreased plasma levels of both dietary and nondietary antioxidants, providing the rationale of antioxidant supplementation in these individuals [18]. One study using ozone-induced challenge in asthma suggested a small, but significant effect of 400 international units of vitamin E/500 mg vitamin C on sulfur dioxide inhalation challenge following ozone exposure; however, other studies of vitamin E supplementation alone have failed to show a therapeutic effect [19,20]. The clinical relevance of these findings needs to be clarified in larger studies. (See "Vitamin intake and disease prevention".)

●Vitamin D – Low serum levels of vitamin D have been associated with severe asthma, raising the question of whether repletion of vitamin D could improve asthma control [17,21]. The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) trial examined this issue in 408 adults with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL [21]. Subjects were randomly assigned to take oral vitamin D₃ (100,000 IU once, then 4000 IU/day for 28 weeks; n = 201) or placebo (n = 207); all subjects took inhaled ciclesonide (320 mcg/d) for the first 12 weeks of the study. Subsequently, if asthma remained controlled, ciclesonide was reduced to 160 IU/day for the next eight weeks, and then 80 IU/day for the final eight weeks. The time to first treatment failure was not different between the groups (adjusted hazard ratio, 0.9 [95% CI, 0.6 to 1.3]), suggesting that vitamin D repletion does not improve asthma control over the short term.

●Vitamins A, C, and E – While vitamins A, C, and E are thought to have anti-inflammatory and/or antioxidant qualities, increased dietary intake of vitamins A and E does not prevent asthma or atopy [22]. A systematic review of vitamin C found insufficient evidence of benefit to recommend vitamin C as a therapeutic agent in asthma [23].

●Omega-3 and omega-6 fatty acids – Omega-3 fatty acids (largely from fish oil) are thought to be anti-inflammatory, while omega-6 fatty acids (largely from nut and plant oils) are precursors to arachidonic acid and are thought to be proinflammatory. Diets rich in anti-inflammatory omega-3 fatty acids have been proposed to be beneficial in the treatment of asthma, although data are conflicting. (See "Dietary fat".)

A systemic review of the literature was unable to find any evidence of benefit, although this was largely attributable to inconsistency in study design and measures of respiratory outcomes [24]. Subsequent to this analysis, one study demonstrated positive effects of omega-3 fatty acids (fish oil supplements) in patients with exercise-induced bronchoconstriction (EIB). This double blind, crossover study randomly assigned 16 subjects to treatment with three weeks of supplements (containing 3.2 g of eicosapentaenoic acid and 2 g of docosahexaenoic acid) or placebo [25]. The group on fish oil supplements had reduced leukotriene, prostaglandin D2 (PGD2), interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha in induced sputa. Bronchodilator use was reduced by approximately 25 percent. After three weeks, subjects receiving fish oil supplementation experienced only an 8 percent decrease in forced expiratory volume in one second (_FEV₁) during exercise challenge, compared with 22 and 21 percent for those on the normal and placebo diets, respectively. This suggests that a diet enriched with omega-3 fatty acids may be helpful in asthmatics with EIB, a finding that warrants further study.

A meta-analysis found no benefit to dietary supplementation with omega-3 or omega-6 fatty acids in the prevention of allergic sensitization [26]. Subsequently, the AsthmaDIET study monitored 135 children with asthma for six months and found that higher dietary omega-6 intake was associated with a greater likelihood of more severe asthma and lower lung function, and also an amplified effect of indoor fine particulate matter (PM 2.5) on asthma symptoms [27]. Relatively higher omega-3 intake was associated with a reduced effect of indoor PM 2.5 on asthma symptoms, but not asthma severity or lung function.

●Soy isoflavone supplementation – It was hoped that dietary ingestion of soy isoflavones would improve asthma control, possibly by the effect of the isoflavone genistein to reduce eosinophil leukotriene synthesis. However, in a 24-week multicenter trial that included 386 adults and children age 12 or older with poorly controlled asthma, isoflavone supplementation (100 mg twice daily) did not significantly improve prebronchodilator forced expiratory volume in one second (FEV₁), symptom scores, episodes of poor asthma control, or exhaled nitric oxide [28].

●DASH diet – The Dietary Approaches to Stop Hypertension (DASH) diet was compared with usual care in a pilot randomized trial of 90 adults with uncontrolled asthma and a low-quality diet [29]. Despite the small study size and short duration, the DASH diet group experienced improvement in the quality of their diet and borderline improvements in asthma control, as assessed by Asthma Control Questionnaire scores (between group difference -0.2, 95% CI -0.5 to 0.1) at six months.

●Low calorie diets – There are very limited numbers of well-performed studies examining low calorie diets in the treatment of asthma [30]. One study from Finland reported that patients with obesity and asthma randomized to a supervised weight reduction program manifested small but significant improvements in lung function and health status [31]. At the end of one year, the FEV₁ had increased more in the low calorie group with a between group difference of 7.6 percent (95% CI 1.5-13.8). It is not known if low calorie diets would benefit people with asthma who do not have obesity.

●Elimination diets – While a rare patient has food allergies, radical alteration of diet or the use of emetic or purgative drugs has no role in asthma treatment [32].

●Magnesium supplementation – Intravenous magnesium is used as adjuvant therapy for acute asthma exacerbations. To determine whether chronic magnesium supplementation would improve asthma control, 55 adults with mild to moderate asthma were randomly assigned to oral magnesium supplementation 340 mg daily or placebo for 6.5 months [33]. Magnesium supplementation was associated with improved asthma control and quality of life and also decreased bronchial hyperreactivity to methacholine challenge, but only a marginal improvement in peak expiratory flow rate. Further evaluation of magnesium supplementation in patients with symptomatic asthma is warranted. Excess oral magnesium ingestion is associated with diarrhea.

BEHAVIORAL THERAPIES — Data are conflicting about the benefit of biofeedback, functional relaxation, and breathing exercises for patients with asthma, although some patients appear to derive benefit.

Biofeedback and functional relaxation — Clinicians, psychologists, social workers, and other mainstream health professionals use biofeedback and relaxation techniques to treat a range of disorders. Most systematic reviews assessing studies of biofeedback and asthma severity have not detected a significant effect [34-36]. However, a subsequently published randomized trial of 94 asthmatic patients found that those trained in heart rate variability biofeedback, with or without breathing modifications, experienced decreased medication usage, fewer symptoms, and improved pulmonary function when compared to a control group [37]. If confirmed in larger trials, this approach may be particularly useful in children. (See "Complementary and integrative health in pediatrics", section on 'Guided imagery, hypnosis, and biofeedback'.)

The effect of functional relaxation and guided imagery techniques on lung function was assessed in a randomized trial that included 64 patients with mild-to-moderate allergic asthma [38]. After four weeks, those in the functional relaxation group experienced an increase in forced expiratory volume in one second (FEV₁) of 7.6 ± 13.2 percent compared with a decrease in FEV₁ of 1.8 ± 11.1 percent in the guided imagery group.

Breathing exercises — Breathing techniques designed to prolong exhalation and decrease minute ventilation have been studied as nonpharmacologic therapies for asthma [39-45]. Pranayama, or yoga breathing exercises, emphasize deep respiration with slow exhalation [39-41,46-49]. Similarly, Buteyko breathing exercises were developed based on the theory that a reduction in minute ventilation might improve asthmatic control [40,42,50].

Although small study sizes and methodologic concerns have hampered progress in this area, data from systematic reviews and randomized controlled trials provide modest evidence of benefit [45,51-58].

●In the largest trial (single blind), 193 patients with moderate-severe asthma were randomly assigned to three sessions of physiotherapist-supervised breathing training or usual specialist care [58]. Patients in the breathing training group had statistically increased improvement in asthma quality of life over one year compared with usual care, although the average difference (0.38 units on the mini-asthma quality-of-life questionnaire) was not clinically significant. No changes were noted in measures of airway physiology, pharmacologic treatments, asthma exacerbations, or exercise capacity. The authors estimated that approximately eight patients would need to be treated to allow one patient to have a clinically meaningful improvement in asthma quality of life due to breathing exercise therapy.

●A separate randomized controlled trial compared use of an expiratory flow-limiting device (designed to simulate Pranayama breathing) with training in Buteyko breathing in 90 asthmatic adults [40]. A control group used a sham device identical to the flow-limiting device, and patients were followed for six months. Neither intervention resulted in decreased bronchial hyperresponsiveness, assessed by methacholine challenge, or improvement in lung function, based on FEV₁. However, patients who used Buteyko breathing reported fewer symptoms and a decrease in the use of inhaled bronchodilators.

PHYSICAL AND ENVIRONMENTAL TECHNIQUES — A variety of physical and environmental techniques have been used to treat asthma. However, high-quality evidence of a clinically significant benefit in asthma is lacking. In part, this is due to a paucity of randomized trials.

Acupuncture — There have been multiple reports of acupuncture as a therapy for asthma. Most studies were uncontrolled, but with positive outcomes [59,60]. In contrast, a prospective sham-controlled crossover study of acupuncture therapy in 20 patients with moderate persistent asthma found that acupuncture was not associated with any improvement in pulmonary function, airway hyperreactivity, or symptoms [61]. Another controlled study again demonstrated no benefit in asthma control with acupuncture [62]. Sixty-six subjects with mild to moderate asthma were randomly assigned to real or sham acupuncture, or no acupuncture at all. Various asthma outcomes were similar in all groups.

A systematic review of 11 randomized trials determined that acupuncture was not associated with significant clinical improvements in asthmatic control [63]. However, the range of trial designs, missing information, and small sample sizes underscored the need for larger, better-designed trials to definitively address the question [2,63].

Chiropractic manipulation — One of the few controlled trials using chiropractic techniques was reported in 80 children who received either active spinal manipulation or a simulated technique [64]. All children were receiving standard medical treatment and had mild to moderate asthma. Outcomes were analyzed at two and four months of therapy, and there were no significant differences noted between groups in morning peak flow rates, symptoms of asthma, use of beta-agonists, quality of life measurements, spirometric measurements, or airway responsiveness. A smaller trial evaluating short-term changes in spirometry after osteopathic manipulation also did not show any benefit compared with usual care [65]. (See "Spinal manipulation in the treatment of musculoskeletal pain".)

Massage therapy — One study that evaluated the effect of parents giving massage therapy to their children for 20 minutes each night before bed yielded interesting results [66]. Children 4 to 8 years of age had better results than those between 9 to 14 years. The younger group showed an immediate decrease in behavioral anxiety and cortisol levels after massage; their attitude toward asthma and their pulmonary function tests also improved over the month of the study. The older group reported lower anxiety and better attitude toward their asthma, but the forced expiratory flow at 25 to 75 percent of forced vital capacity (FEF 25-75) was the only spirometric parameter that improved. Further research is needed to determine whether the benefits of massage therapy are reproducible and durable.

Physical training — Even though exercise is a trigger of asthma symptoms for many people with asthma, regular physical training may have a beneficial effect in stable asthma. In a systematic review, physical training (eight studies with 267 participants) for subjects with asthma was associated with improved cardiopulmonary fitness as measured by a significant increase in maximum oxygen uptake [67]. Pulmonary function parameters were unimproved, but positive effects in health-related quality of life were noted on four of five studies. No adverse effects were reported. In a separate assessor-blinded study of 150 patients with asthma randomized to intensive interval training or usual care, the training group demonstrated a 24 percent reduction in inhaled glucocorticoid therapy over six months (-233 micro-g versus +2 micro-g budesonide, 95% CI -391 to -77 micro-g), but failed to achieve the primary outcome of a mean dose reduction of 25 percent or more [68]. More research is needed to determine the optimal way to incorporate physical training in asthma management.

Speleotherapy and halotherapy — Speleotherapy and halotherapy are types of "physical therapies" that have been pursued in countries of the former Soviet Union to avoid the costs and side effects of drug-based therapies, as well as the problems of microbial and tumor resistance. Thus, the majority of the clinical trials are reported in Russian-language journals and have focused on the treatment of asthma, chronic bronchitis, and other respiratory diseases. Physical therapies are most commonly used in spas in central and eastern Europe and around the Dead Sea in Israel.

Speleotherapy involves spending time in underground environments (from "speleos," which is Greek for cave). People spend short periods in specifically designated caves or mines, sometimes doing particular physical or breathing exercises. Some forms involve longer stays on special wards. Speleotherapy is most commonly used in northern Mediterranean and Aegean Sea cultures. Benefit is believed to result from air quality, air pressure, underground climate, or radon or radiation exposure. No evidence from randomized trials has demonstrated an effect greater than placebo [34,69].

Halotherapy (from "halos," Greek for salt) uses dry aerosol microparticles of salt or minerals to simulate the microclimate of salt mines. It has been used to treat a variety of "chronic" respiratory diseases including asthma and, occasionally, upper respiratory problems such as chronic sinusitis [70-73]. The effect of halotherapy was examined in 29 patients with moderate asthma who were randomly assigned to halotherapy or placebo inhalation five times a week for two weeks [74]. Bronchial responsiveness to histamine challenge decreased slightly in the halotherapy group. In a separate trial, peak expiratory flow and rescue bronchodilator use did not differ between active and placebo groups [75].

SUMMARY AND RECOMMENDATIONS

●Integrative medicine is patient-centered care that focuses on the whole person; is informed by evidence; and makes use of all appropriate therapeutic approaches, healthcare professionals, and disciplines to promote optimal health and healing. (See 'Overall efficacy' above.)

●Complementary and alternative medicine (CAM) typically is used as an adjunct rather than an alternative to mainstream medical care. Patients and caregivers may turn to CAM therapists who offer them personal attention, hope, time, and therapies consistent with their values, world view, and culture. Complementary therapies are a subset of integrative medicine. (See 'Overall efficacy' above.)

●Evidence supporting the use of complementary and alternative medical approaches to improve asthma management is limited. Most studies suggest that such an effect, if present, is small. The risks and benefits of such an approach should be considered on a case-by-case basis. (See 'Overall efficacy' above.)

●For patients who seek CAM due to poorly-controlled asthma, the "first alternative therapy" should be frequent patient visits, even at weekly intervals. This will hopefully strengthen the patient-physician partnership and improve compliance; evaluation of inhaler technique can be done with corrections, as needed. These steps may obviate the need for "alternative agents." (See 'Overall efficacy' above.).

●It is very difficult to study the impact of dietary changes upon the course of asthma, and most studies show no effect, including those of antioxidants; vitamins A, C, D, and E; and soy isoflavones. While small studies suggested a modest benefit with fish oil supplements (omega-3 fatty acids) and magnesium supplements, further study is needed. (See 'Dietary changes and supplements' above.)

●The US Food and Drug Administration (FDA) has issued a warning to consumers not to rely on homeopathic products for asthma, as they have not undergone testing for efficacy. (See 'Homeopathy' above and "Homeopathy".)

●Data are conflicting about the benefit of biofeedback, functional relaxation, and breathing exercises for patients with asthma, although some patients appear to derive benefit. (See 'Behavioral therapies' above.)