CAM and its use in Allergic Diseases

1. CAM and its use in Allergic Diseases Julie Wang, MD Mount Sinai School of Medicine New York, NY October 21, 2012

2. Objectives • Identify different modalities of CAM • Describe a few types of CAM that may be used by patients • Understand current regulation of CAM

3. What is CAM? • Complementary and alternative medicine • Group of diverse medical and health care, systems, practices, and products that are not generally considered part of conventional medicine • NIH formed the National Center for Complementary and Alternative Medicine (NCCAM) in 2008 • Mission: To define, through rigorous scientific investigation, the usefulness and safety of complementary and alternative medicine interventions and their roles in improving health and health care. Nccam.nih.gov

4. 4 Basic Domains of CAM • Mind-body medicine – ie. meditation, prayer, yoga • Biologically based practices – ie. herbs, foods, vitamins, minerals • Manipulative and body-based practices – ie. chiropractic manipulation, massage • Energy medicine – ie. biofield therapy, biomagnetic-based therapies Nccam.nih.gov

5. History of CAM • Developed in a number of cultures, based on the teacher-apprentice model, observations and experiences • Western medicine is based on the scientific methods, “evidence-based” medicine (evidence is what is currently available at the time) Chang and Gershwin. Clinic Rev Allerg Immunol 2012

6. Why should we learn about CAM? • 2007 NIHS – 38% adults and 12% children had used CAM in the past year (ie. Natural products, breathing exercises, etc) • Annual expenditure for CAM is >$30 billion • NCCAM budget for 2011 was $127.7 million • Predictors of CAM use – highly educated in poor health with multiple medical problems, association with activism and history of a transformative experience Barnes et al. Adv Data 2002 Lundgren and Ugalde. Phys Med Rehabil Clin N Am 2004

7. Research in CAM • Consortium of Academic Health Centers for Integrative Medicine • Mission: To advance the principles and practices of integrative healthcare within academic institutions • Mount Sinai Medical Center • Boston University • Harvard Medical School • University of Connecticut • University of Vermont • Yale University • Duke • Stanford • Johns Hopkins • Many others www.imconsortium.org

8. Research in CAM • With NIH/NCCAM support, various therapies are being rigorously explored in the field of A/I: • Chinese herbal medication for food allergies • SLIT for peanut allergy • Vitamin D and mucosal immunity

9. CAM in Asthma: Acupuncture • Rationale: Uncertain; possible stimulation of adrenocorticotropic hormone, VIP, or endorphins, leading to increased secretion of adrenocorticoids and increased steroid production • Randomized controlled study as add-on for inpatients with asthma – improved PEF variability and anxiety, but no change in objective lung functions • Randomized pilot study of acupuncture as adjunct to conventional therapy in adults – improved quality of life, but no difference in pulmonary functions Scheewe et al. Complement Ther Med 2011 Choi et al. J Asthma 2010

10. CAM in Asthma: Acupuncture • Cochrane review, which included 11 studies, showed insufficient evidence to recommend acupuncture for chronic asthma • Potential risks: • Unsterile needles – infection • Improper placement of needles – reports of pneumothorax, subarachnoid hemorrhage • Bruising McCarney et al. Respir Med 2004 He et al. J Altern Complement Med 2012 Kmietowicz. BMJ 2012

11. Breathing retraining: rationale • Buteyko – shallow, controlled breathing and respiratory pauses to increase alveolar and arterial CO2 tension which may reverse bronchospasm • Yoga – deep breathing exercised, posture, mucus expectoration, meditation, prayer to reduce asthma symptoms • Respiratory muscle training – strengthen muscles to meet the increased work of breathing in asthma Burgess et al. Expert Rev Respir Med 2011

12. Breathing retraining for asthma • Systematic review of RCTs (n=41) indicate beneficial effects for quality of life with yoga, Buteyko breathing technique, and physiotherapist-led breathing training • While these will not replace standard asthma medications, these modalities are readily available and may be helpful as complementary therapy Burgess et al. Expert Rev Respir Med 2011

13. Vitamin D and Asthma • CAMP study, n=1024, 10% were vitamin D deficient • Controlled for age, sex, race, BMI, history of ER visits, and seasons • Concluded that vitamin D supplementation may enhance anti-inflammatory effects of ICS in pediatric asthma Wu et al. Am J Respir Crit Care Med 2012

14. Vitamin D and Asthma • N=48 children, 5-18 years • No prior use of corticosteroids (inhaled, oral or intranasal) • Randomized, double-blind, parallel group, 6 month trial • Inhaled budesonide 800 mcg/day DPI +/- vitamin D 500IU Majak et al. J Allergy Clin Immunol 2011

15. Probiotics for Atopic dermatitis • Rationale: Reduce intestinal inflammation and permeability and/or modify intestinal microbiota which results in modulation of immune responses • Cochrane review identified 12 trials of probiotic use for the treatment of eczema • No significant reduction in symptoms or investigator rated severity • Different probiotic strains, different measures of atopic dermatitis Boyle et al. Clin Exp Allergy 2009

16. Probiotics: AD prevention? Pelucchi et al. Epidemiology 2012

17. Probiotics for AD • Perhaps effects of probiotics may be sufficient to prevent atopic dermatitis, but not effective enough to treat already established disease • Risks: Case reports of sepsis and bowel ischemia (risk factor – severe acute pancreatitis) Pelucchi et al. Epidemiology 2012 Besselink et al. Lancet 2008

18. Fish oil for AD • Rationale: decrease redness, scaling, and itching by reducing inflammatory components of atopic dermatitis • Double-blind, randomized studies • Fish oil 10g/day vs olive oil x 12 weeks (n=31) • Fish oil 6 g/day (n-3 fatty acids) vs corn oil x 4 mo (n=145) • May be modest effect on AD • Risks: generally well-tolerated Bjorneboe et al. J Intern Med Suppl1989 Soyland et al. Br J Dermatol 1994

19. Vitamins for AD • Rationale: • Vitamin D – induces cathlecidin production, topical vit D has inhibitory effect of IgE-mediated cutaneous reactions • Vitamin E – antioxidant properties

20. Vitamin D and E for AD • Study of 11 children randomized to vitamin D 1000 IU vs placebo for 1 month (n=11) • No difference in IGA or EASI scores • Vitamin D 1600 IU, vitamin E 600 IU, or both vs placebo x 60 days (n~11 per group) • Improvement in SCORAD Sidbury et al. Br J Dermatol 2008 Javanbakht et al. J Dermatolog Treat 2011

21. Vitamin risks • Excess vitamin D can lead to hypercalcemia • Vitamin E may increase risk for stroke; High doses can also cause nausea, diarrhea, stomach cramps, fatigue, weakness, headache, blurred vision, rash, and bruising and bleeding

22. CAM in Allergic rhinitis: Butterbur • Rationale: petasin, an active ingredient, inhibits leukotriene synthesis in vitro, decreases nasal histamine and leukotriene levels in vivo • Clinical trials: • Significant symptom improvement and QOL compared to placebo in 3 RCTs • similar benefit to antihistamines (cetirizine 10mg or fexofenadine 180mg/day) in 2 RCTs • 1 trial showed no difference compared to placebo Guo et al. Ann Allergy Asthma Immunol 2007

23. CAM in Allergic rhinitis: Butterbur • Major concern is the hepatotoxic pyrrolizidine alkaloid (PA) content in some butterbur products; may also have pulmonary and hematologic effects; potential carcinogen • May cause allergic reactions for ragweed allergic individuals • Headache, itchy eyes, diarrhea, asthma, pruritus, stomach upset, fatigue, and drowsiness Giles et al. J Herb Pharmacother 2005

24. CAM in Allergic rhinitis: Aller-7 • Composed of standardized extract of 7 Indian medicinal plants: • Phyllanthus emblica (fruit), Terminalia chebula (fruit), Terminalia bellerica (fruit), Albizia lebbeck (bark), Zingiber officinale (ginger root), Piper longum (fruit) and Piper nigrum (fruit – black pepper) • Proposed effects: Anti-inflammatory and antioxidant effects seen in animal models D’Souza et al. Drugs Exp Clin Res 2004 Pratibha et al. Int J Tissue React 2004

25. CAM in Allergic rhinitis: Aller-7 • Some improvement in symptoms of AR demonstrated in 2 RCTs, but used different endpoints • Risks: Laxative effects, nausea, vomiting Vyjayanthi et al. Res Commun Pharmacol Toxicol 2003 Saxena et al. In J Clin Pharmacol Res 2004

26. CAM: Are you convinced? • Mostly small sample sizes • Heterogeneity in study designs • Variations in inclusion criteria • Variations in endpoints • Lack of placebo • Lack of blinding • Therefore, current studies do not show robust data in support of clinical use at the present time. • However, cannot exclude the possibility of modest effects

27. Next steps for research • Safety • Adverse effects of therapy • Potential interactions with other natural products or conventional mediations/therapies • Efficacy • Elucidate mechanisms of action • Identify active ingredients • Compare CAM as monotherapy vs CAM as adjunctive treatment

28. Government regulation:Dietary Supplement • Dietary Supplements – a product that contains vitamins, minerals, herbs or other botanicals, amino acids, enzymes, and/or other ingredients intended to supplement the diet. • FDA has special labeling requirements for dietary supplements and treats them as foods, not drugs. • A manufacturer does not have to prove the safety and effectiveness of a dietary supplement before it is marketed. • Once a dietary supplement is on the market, the FDA monitors safety and product information (label claims and package inserts), and the Federal Trade Commission (FTC) monitors advertising.

29. Government regulation:Practitioner-Based Therapy • There is no standardized, national system for credentialing CAM practitioners. • The extent and type of credentialing vary widely from state to state and from one CAM profession to another • some CAM professions (e.g., chiropractic) are licensed in all or most states, although specific requirements for training, testing, and continuing education vary • other CAM professions are licensed in only a few states or not at all

30. Risks of CAM to consider • Predictable and expected adverse reactions • Idiosyncratic reactions • Product quality – handling and manufacturing, contamination, substitutions, misidentifications of materials, adulteration (ie. with steroids), lack of standardization, incorrect preparation of dose, incorrect labeling and advertising • Use of CAM may lead to interruption of conventional therapies because misunderstanding or incorrect assumption that “natural” equates with “safe”

31. Effect of CAM use on standard medication adherence • Pediatric asthma patients (n=187) • Medication adherence report scale, reported missed doses of standard asthma medication • 18% used CAM; no difference between groups in terms of adherence with standard asthma medications • Adult asthma patients (n=327) • Medication adherence report scale • 25% used herbal therapies • CAM use associated with decreased ICS adherence and increased asthma morbidity (OR 0.4, 95% CI 0.2-0.8) Philp et al. Pediatrics 2012 Roy et al. Ann Asthma Allergy Immunol 2010

32. When your patient is usingor considering CAM • Determine and document risk levels based on review of medical literature on safety and efficacy • Provide adequate informed consent and document the consent process • Continue to monitor the patient throughout the therapy • Document if CAM provider is involved • Report any adverse events

33. Where to get more information • NCCAM website • Natural Medicines Comprehensive Database • Natural Standard • Evidence based information on CAM – natural ingredients, supplements • Searchable by commercial brand names • Information on safety and efficacy • May need membership