QUESTION: Can You Recommend a Systemic Approach to Asthma?

ANSWER: The global rise in the rate of asthma over the past 50 years is considered epidemic. Although all of the factors behind this rise are not clearly understood, many are and the good news is that most are correctable. This disease currently affects more than 22 million people in the U.S. alone, including six million children with a cost in 2007 of US $56 billion.(1,2) This chronic inflammatory disorder is characterized by a complex interaction of airflow obstruction, bronchial hyper-responsiveness and an underlying inflammation.(3) Conventional therapy, (often a combination of an inhaled corticosteroid and a beta-agonist), can reduce symptoms and prevent airway remodeling (a sign of more permanent damage), but it does not address underlying causes, and when it is stopped the symptoms return full force.(4) Additionally, long-term use of these medications has been associated with adverse effects including adrenal suppression at high dose, as well as increased infections and impaired growth in children.(5)
We’d like to review some of the recent research, which helps explain its rapid growth, and highlight a few natural therapies for both the prevention and treatment of asthma. For example, vitamin D deficiency and the dramatic rise in obesity are likely important drivers of the asthma epidemic. Viewing asthma as connected to more systemic physiological function rather than as an isolated disease, as well as understanding the different etiologies of asthma (versus simply prescribing for a diagnosis of asthma) provide a more optimal approach to this chronic condition.

Weight Control & Insulin Resistance

Research over the last 10 years has found a link between asthma and obesity, and the development of obesity prior to asthma suggests it might actually be a causal factor.(6) Not only does obesity increase the risk for asthma by two to three fold, but it also is associated with more emergency room visits, medication use and resistance, and overall symptoms among those with asthma.(7) Body mass index (BMI) is directly proportional to the risk for asthma among those with an elevated BMI, i.e. there is a “dose effect” of weight on asthma risk. Additionally, the link between asthma and overweight/obesity is present in children as young as 3 years old.(8) The rapid rise in obesity, as demonstrated by a prevalence three times as higher in children than 30 years ago, may help to explain the alarming trend in asthma rates.(9)
A link between asthma and a metabolic syndrome seems very likely, as one study of over several thousand adults found that insulin resistance was predictive of asthma symptoms, even more so than obesity.(10) Indeed, a study of nearly 18,000 children found that higher triglyceride levels and acanthosis nigricans (signs of insulin resistance) were predictive of asthma in children, regardless of body mass index.(11)
The asthma associated with obesity also appears to be a distinct entity, i.e. it is different than atopic asthma, and will likely improve with different treatments. For example, conventional medications are less effective in overweight patients.(12) Fortunately, weight loss in overweight individuals with asthma is likely to help reduce many of the underlying factors, such as airway hyperresponsiveness.(13) A review of weight loss among asthmatics documented improvement in all 15 studies included for analysis.(14) We’re still waiting on the results of a randomized intervention (the BE WELL trial)(15), but the Mediterranean diet, which is likely to help reduce both body weight and inflammation, appears to be associated with a lower risk for asthma as well as better asthma control among children and adults.(16,17)

Vitamin D

Once again, vitamin D has emerged as being an important risk factor for yet another chronic inflammatory disease. One recent study in children found a vitamin D deficiency to be the strongest risk factor for developing asthma, associated with a nearly five-fold increase in risk.(18) Low vitamin D levels may also affect airway remodeling and disease severity, particularly in those who are resistant to steroids.(19) Recent research suggests a role for vitamin D not just in reducing inflammation, but also for regulating immune function in the lung.(20) It may also be a link between increased atopy and food allergies among those with asthma, and an increased reactivity to exercise.(21,22)

Allergies & Immune Programming

There is an established role for allergies among individuals with asthma, though it may be clinically relevant in less than half of all patients.(23) For example, food allergies increase the risk for asthma by almost four-fold, and the odds of visiting an emergency room in the last year for an attack by seven-fold.(24) This connection is likely a consequence of immune programming early in life. Once termed the “hygiene hypothesis” and now as the “early programming hypothesis,” a considerable amount of evidence links both in-utero and newborn exposure to environmental chemicals, viruses, a Western diet, and perhaps most importantly, gut microbes, to an increased risk for asthma. For example, exposure to the right microbes (in breast milk, soil, water, etc.) may help teach the immune system to differentiate commensal organisms from pathogens, and produce anti-inflammatory rather than pro-inflammatory cytokines.(25) This may help to explain the increase in risk for asthma associated with lack of breast-feeding, antibiotic use, caesarian sections and other environmental antigens, and why probiotic supplementation may be an important intervention.(26)

Environmental Toxins

There are many factors that appear to contribute to the development and progression of asthma, only some of which we’ve highlighted here. For example, smoking and both indoor and outdoor air pollution are important contributors to asthma prevalence and severity.(27,28) It follows that supporting phase II detoxification, particularly in those with genetic susceptibilities, will be an effective therapy for children with environmental triggers, and research supports this strategy.(29,30)

Antioxidants

Other important nutritional therapies are antioxidants such as vitamin C, lycopene and pycnogenol, all of which have shown to reduce asthma symptoms or prevalence.(31-34) Choline and n-3 fatty acid supplementation have also shown clinical benefit for asthmatic patients.(35-37)

Conclusion

Nutritional supplementation, combined with identification of food and environmental allergies, improving air quality, adherence to a Mediterranean diet, maintaining optimal vitamin D levels and losing excess weight are powerful therapies for asthma prevention and treatment. Given the potential risk of changing asthma medications, it is important to seek the help of a qualified practitioner before changing existing therapies.

References:

1. National Asthma Education and Prevention Program Coordinating Committee. Expert Panel Report (EPR3): Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.

2. Barnett SB, et al. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011 Jan;127(1):145-52.

3. Tesse R, et al. Asthma and endocrine disorders: shared mechanisms and genetic pleiotropy. Mol Cell Endocrinol. 2011 Feb 20;333(2):103-11.

4. Guilbert TW, et al. Long?term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985?1997.

5. Mark JD. Pediatric asthma: an integrative approach to care. Nutr Clin Pract. 2009 Oct-Nov;24(5):578-88.

6. Farah CS, et al. Asthma and obesity – a known association but unknown mechanism. Respirology. 2011 Oct 12. doi: 10.1111/j.1440-1843.2011.02080.x. [Epub ahead of print]

7. Stingone JA, et al. Prevalence, Demographics, and Health Outcomes of Comorbid Asthma and Overweight in Urban Children. J Asthma. 2011 Sep 29. [Epub ahead of print]

8. Suglia SF, et al. Asthma and obesity in three-yearold urban children: role of sex and home environment. J Pediatr. 2011 Jul;159(1):14-20.e1.

9. Ogden CL, et al. Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA. 2010 Jan 20;303(3):242-9.

10. Thuesen BH, et al. Insulin resistance as a predictor of incident asthma-like symptoms in adults. Clin Exp Allergy. 2009 May;39(5):700-7.

11. Cottrell L, et al. Metabolic abnormalities in children with asthma. Am J Respir Crit Care Med. 2011 Feb 15;183(4):441-8.

12. Lugogo NL, et al. Does obesity produce a distinct asthma phenotype? J Appl Physiol. 2010 Mar;108(3):729-34.

13. Dixon AE, et al. Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol. 2011 Sep;128(3):508-15.e1-2.

14. Eneli IU, et al. Weight loss and asthma: a systematic review. Thorax. 2008 Aug;63(8):671-6.

15. Ma J, et al. The Breathe Easier through Weight Loss Lifestyle (BE WELL) Intervention: a randomized controlled trial. BMC Pulm Med. 2010 Mar 24;10:16.

16. Arvaniti F, et al. Adherence to the Mediterranean type of diet is associated with lower prevalence of asthma symptoms, among 10-12 years old children: the PANACEA study. Pediatr Allergy Immunol. 2011 May;22(3):283-9. doi: 10.1111/j.

17. Barros R, et al. Adherence to the Mediterranean diet and fresh fruit intake are associated with improved asthma control. Allergy. 2008 Jul;63(7):917-23.

18. Bener A, et al. Vitamin D Deficiency as a Strong Predictor of Asthma in Children. Int Arch Allergy Immunol. 2011 Oct 6;157(2):168-175. [Epub ahead of print]

19. Gupta A, et al. Relationship Between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma. Am J Respir Crit Care Med. 2011 Sep 15. [Epub ahead of print]

20. Iqbal SF, et al. Mechanism of Action of Vitamin D in the Asthmatic Lung. J Investig Med. 2011 Sep 21. [Epub ahead of print]

21. Bozzetto S, et al. Asthma, allergy and respiratory infections: the vitamin D hypothesis. Allergy. 2011 Sep 21. doi: 10.1111/j.1398-9995.2011.02711.x. [Epub ahead of print]

22. Chinellato I, et al. Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma. Eur Respir J. 2011 Jun;37(6):1366-70.

23. Sunyer J et al. Geographic variations in the effect of atopy on asthma in the European Community Respiratory Health Study. J Allergy Clin Immunol. 2004 Nov;114(5):1033-9.

24. Liu AH, et al. National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2010 Oct;126(4):798-806.e13.

25. Kozyrskyj AL, et al. Early life exposures: impact on asthma and allergic disease. Curr Opin Allergy Clin Immunol. 2011 Oct;11(5):400-6.

26. Singh M, Ranjan Das R. Probiotics for allergic respiratory diseases—putting it into perspective. Pediatr Allergy Immunol. 2010 Mar;21(2 Pt 2):e368-76.

27. McCormack MC, et al. Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma. Ann Allergy Asthma Immunol. 2011 Apr;106(4):308-15.

28. Butz AM, et al. A randomized trial of air cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke exposure. Arch Pediatr Adolesc Med. 2011 Aug;165(8):741-8.

29. Searing DA, et al. Environmental pollution and lung effects in children. Curr Opin Pediatr. 2011 Jun;23(3):314-8. doi: 10.1097/MOP.0b013e3283461926.

30. Wan J, Diaz-Sanchez D. Phase II enzymes induction blocks the enhanced IgE production in B cells by diesel exhaust particles. J Immunol 2006; 177:3477–3483.

31. Allen S, et al. Association between antioxidant vitamins and asthma outcome measures: systematic review and meta-analysis. Thorax. 2009 Jul;64(7):610-9.

32. Tecklenburg SL, et al. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med. 2007 Aug;101(8):1770-8.

33. Lau BH, et al. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma. 2004;41(8):825-32.

34. Neuman I, et al. Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy. 2000 Dec;55(12):1184-9.

35. Mehta AK, et al. Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma. Immunobiology. 2010 Jul;215(7):527-34.

36. Minns LM, et al. Toddler formula supplemented with docosahexaenoic acid (DHA) improves DHA status and respiratory health in a randomized, double-blind, controlled trial of US children less than 3 years of age. Prostaglandins Leukot Essent Fatty Acids. 2010 Apr- Jun;82(4-6):287-93.

37. Mickleborough TD, et al. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest. 2006 Jan;129(1):39-49.