Mohamed, Nagwa H.a; Abdel Meguid, Iman E.b; Shaaban, Hala H.b; Ahmed Kamel, Inas M.a
Asthma is the most common chronic disease of childhood. It is a chronic inflammatory disorder of the airways characterized by an obstruction of airflow, which may be reversed completely or partially with or without specific therapy 1.
Airway inflammation is the result of interactions between various cells, cellular elements, and cytokines in susceptible individuals 2.
In Egypt, the prevalence of asthma is higher in 5–10-year-old students (13%) compared with 11–15-year-old students (10%) 3.
Pathophysiology and pathogenesis of asthma
Interactions between environmental and genetic factors result in airway inflammation, which limits airflow and leads to bronchospasm, mucosal edema, and mucus plugs.
Interleukin-6 (IL-6) is a cytokine that acts both as a proinflammatory and as an anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage, leading to inflammation. In terms of host response to a foreign pathogen 4, studies using IL-6 suggest that IL-6 protects against airway inflammation, whereas studies using neutralizing antibodies suggest that IL-6 promotes allergic airway inflammation 5.
Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but is associated with loss of central airway function 6.
Immunoglobulin E (total and specific)
Total serum immunoglobulin E (IgE) is a risk factor for both the development of and disease severity in asthma. The production of IgE is controlled by a complex regulatory process that ultimately involves isotype class switching by mononuclear B lymphocytes, a CD4+ T-cell-dependent process 7. It has been reported that parenchyma of inflamed lungs has an airway antigen challenge and these contain IgG-producing and IgE-producing plasma cells, shown to produce the corresponding isotypes, when isolated from the lungs and then cultured in vitro. Locally produced IgE as well as circulating IgE are likely to sensitize mast cells in the airways 8.
Clinical grading of asthma
The management of asthma is based on four principles (Table 1):
Control of symptoms, including nocturnal symptoms and those related to exercise.
Prevention of exacerbations and need for rescue medication.
Achievement of the best possible lung function [forced expiratory volume (FEV)1 and/or peaked expiratory flow rate (PEFR)>80%)].
Minimize side effects.
Long-term medications include the following:
Inhaled corticosteroids is, used in patients with persistent asthma 10.
Leukotriene receptor antagonists to reduce the symptoms of asthma 11.
Cromolyn/nedocromil sodium, which is a mast cell stabilizer used extensively for asthma prophylaxis 12.
Immunomodulators: such as omalizumab (anti-IgE) for subcutaneous use for long-term control and prevention of symptoms in adults (≥12 years old) who have moderate or severe persistent allergic asthma 13.
Theophylline, which is a long-acting β2-agonist for long-term prevention of symptoms 14.
Quick relievers include the following:
Short-acting β2-agonists, used as initial therapy in children with asthma 15.
Ipratropium bromide, which is not used frequently 16.
There has been an increase in the use of complementary and alternative medicine (CAM) as a healthcare option in recent years worldwide. According to the WHO, more than three-quarters of the world’s population rely on CAM for healthcare 17.
Effect of acupuncture in bronchial asthma
Acupuncture stimulates the release of β endorphin, which, coupled with the release of adrenocorticotrophic hormone, acts on the adrenal cortex to stimulate the release of cortisol, inducing another possible anti-inflammatory effect 18.
It also exerts a vasodilative effect caused by the release of calcitonin gene-related peptide upon stimulation of nerve fibers 19.
The release of anti-inflammatory cytokines could be induced from lymphocytes and secondary activating cells, such as macrophages 20.
Direct bronchodilation effect of acupuncture
Asthmatic patients showed an immediate bronchodilating response of FEV1 after acupuncture, and a similar bronchodilator response was reproducible with repeated acupuncture, and it leads to a short-term reduction in airway resistance 21.
Aim of the work
The aim of our work is to assess the effect of traditional Chinese acupuncture in children with bronchial asthma on clinical conditions, pulmonary function (vital capacity (VC)%, forced vital capacity (FVC)%, FEV1%, forced expiratory flow (FEF)25–75%, PEF%, FEF25%, FEF50%, and FEF75%), eosinophilic count, IgE, and IL-6.
Patients and methods
This was a clinical trial conducted at the acupuncture clinic of the medical service unit at the national research centre of Egypt during the period from October 2010 to April 2011 on 30 children with chronic bronchial asthma who were followed up for their asthma in the outpatient clinic of asthma and allergy for children in the Abu-Elrish hospital, pediatric hospital of Cairo University.
All the patients had an established clinical history of asthma (partially controlled and uncontrolled asthma according to the GINA criteria), and they ranged in age from 7 to 16 years; there were free from other major health problems and were receiving conventional medical treatment for not less than 3 months.
All the patients included in the study were subjected to the following before and after the acupuncture sessions:
Asthma history taking.
Thorough clinical examination.
Investigations include the following:
Pulmonary function testing by spirometry (Fukuda Denshi Spirosift SP-5000).
Complete blood count (especially the eosinophilic count), total serum IgE, and serum IL-6.
Each patient was subjected to a needle acupuncture session three times per week for 4 weeks by application of a filiform disposable needle on each of the points selected according to traditional Chinese medicine for 20 min.
The points were selected according to traditional Chinese medicine along the following energy meridians: (Lu-4,7,9), (LI-4), (Bl-13,23), (Ren 17), (St-36), (Sp-6).
Informed consent was obtained from the parents before starting the study according to the scientific ethical committee rules of the National Research Centre and Hospitals of Cairo Universities.
The study included 10 female and 20 male children with asthma (Figs 1–4 and Tables 2–7).
We observed that there were reduction in IL-6 only by 30%, IgE only by 26.7% and in both by 36.7%.
The chronicity of bronchial asthma and fear of steroid therapy lead many patients to seek alternative methods of treatment.
Acupuncture has traditionally been used in asthma treatment in China and is increasingly being used in western countries. Although there are many published studies on acupuncture and asthma, few fulfill the scientific criteria necessary to prove the effectiveness of acupuncture.
According to the GINA classification, the number of patients free from attacks increased to 10 after the acupuncture sessions (33.3%); intermittent attacks, which were earlier seen in five patients (16.7%), increased to 16 patients (53.3%) after the acupuncture sessions, but moderate persistent attacks, which were earlier seen in 21 patients (70%), were not seen in any patient after the acupuncture sessions.
Ahrens et al. 22 reported mild clinical benefits in bronchial asthma in terms of symptoms and signs, which is in agreement with our study. This is also in agreement with Neveu et al. 23, who concluded that active acupuncture induces additional clinically significant improvement in the quality of life and symptoms of dyspnea in asthmatic patients who are under therapeutic management.
Joos et al. 17 showed that acupuncture had an immediate effect in relieving the symptoms of asthma.
The results of the current study indicated a decrease in the eosinophilic count after acupuncture sessions. This finding is agreement with that of Jeong et al. 24, who examined the short-term and long-term effects of real versus sham acupuncture in patients with bronchial asthma, but our study showed greater significant reduction in the eosinophilic count because of the longer duration of our intervention.
Joos et al. 17 concluded, in his randomized-controlled study on the immunomodulatory effects of acupuncture on inflammatory cells and cytokines in some asthma patients, that there were significant decreases in cytokines IL-6 (P=0.026). In our study, there was no significant decrease, perhaps because of the wide range in our laboratory results of IL-6.
Petti et al. 25 reported beneficial effects of acupuncture as a CAM for children with bronchial asthma and suggested that the decrease in IL-6 may indicate an improvement in the immune system of patients with allergic asthma because of IL-6 production of numerous effector mechanisms in the pathogenesis of allergic asthma.
All pulmonary function parameters assessed in the study showed significant improvements after acupuncture sessions; the VC% improved from 62.7±14.2 to 75.2±12.3 (P<0.001) and the FVC% from 49.1±13.8 to 64±14.2 (P<0.001). Also, the FEV1% improved from 53.6±15.0 to 69.2±14.1 (P<0.001). The FEF25–75% decreased with resistance in small-sized and medium-sized bronchioles and also improved from 67.9±17.0 to 91.6±16.2 (P<0.001); PEF% improved from 53±13.6 to 68.7±10.6 (P<0.001), FEF25% from 2.2±0.7 to 2.8±0.7 (P<0.001), FEF50% from 1.6±0.5 to 2.2±0.5 (P<0.001), and FEF75% from 1.1±0.5 to 1.6±0.6 (P<0.001).
The results of Barton 26 were in agreement with ours as he found that the pulmonary function test showed an immediate improvement. The results of Kuo-Chu et al. 21 are also in agreement with ours in his conclusion that the use of acupuncture for 12 days resulted in a significant improvement in all pulmonary functions, except the FEV1/FVC ratio in patients with moderate and severe asthma. We obtained the same result but with a minimal increase in the value of the FEV1/FVC ratio, perhaps because of the severity and the chronicity of the disease, which affect the bronchial patency.
In this study, we observed that in patients who showed a reduction in the levels of both IL-6 and IgE, there was a significant improvement in the means of VC% from 66.6±13.3 to 79.1±11.2 (P=0.012) after acupuncture sessions, FVC% from 53.8±12.6 to 63.9±11.9 (P=0.035), FEV1% from 59.1±13.6 to 70.5±12.8 (P=0.026), FEF25–75% from 74.5±14.6 to 97.0±12.2 (P=0.002), and PEF% from 56.6±12.4 to 70.5±7.6 (P=0.002); after the acupuncture sessions, FEF25% improved from 2.3±0.7 to 2.9±0.05 (P=0.004), FEF50% improved from 1.7±0.5 to 2.3±0.4 (P<0.001), and FEF75% improved from 1.2±0.5 to 1.6±0.4 (P=0.005). This improvement in the pulmonary functions in this group was not significantly different in comparison with the total group; thus, we need further studies to correlate the improvement in pulmonary functions and the reduction in cytokines in the blood in a larger number of patients and longer durations of acupuncture sessions.
The chronicity of bronchial asthma and fear of steroid therapy lead many patients to seek alternative methods of treatment such as acupuncture. Acupuncture has an effect on bronchial asthma through its anti-inflammatory effect as it can modulate the levels of cytokines and other anti-inflammatory mediators.
A direct bronchodilating effect was observed in patients, who showed an immediate bronchodilating response of FEV1 after acupuncture, and a similar bronchodilator response was reproducible with repeated acupuncture sessions.
We found a significant improvement in many parameters: clinical (symptoms, signs, frequency of attacks, night awakening) and pulmonary functions (VC%, FVC%, FEV1%, FEF25–75%, PEF%, FEF25%, FEF50%, and FEF75%). However, there were reductions in the medication used, for example, bronchodilators, corticosteroids, and mast cell stabilizers.
Patients also showed a significant decrease in eosinophilic counts and a nonsignificant decrease in IL-6 and IgE.
Acupuncture sessions for children with bronchial asthma result in measurable improvement in clinical condition, pulmonary functions, and cytokines.
Table. No title avai...Image Tools
Conflicts of interest
There are no conflicts of interest.
1. Valet Robert S.of Vanderbilt University School of Medicine in Nashville. Rural kids have more asthma, get less medicine.Clin Exp Allergy2011;41:482–489.
2. Sharma GD, Gupta P.Fellow in Allergy and Immunology, Long Island College Hospital/SUNY Downstate, Contributor Information and Disclosures: 2010.
3. Ali A, Sallam MM, Fathy GA, El Din OMohy, Awad SA, Ahmed A.Epidemiological study of the prevalence of bronchial asthma and other atopic diseases among school children in Egypt.Int J Acad Res2010;2:217–219.
4. Benedict C, Scheller J, Rose-John S, Born J, Marshall L.Enhancing influence of intranasal IL-6 on slow-wave activity and memory consolidation during sleep.FASEB J2009;23:3629–3636.
5. Doganci A, Eigenbrod T, Krug N, De Sanctis GT, Hausding M, Erpenbeck VJ, et al..The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo.J Clin Invest2005;115:313–325.
6. O’Hollaren MT, Limb SL, Brown KC, Wood RA.NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment – 2004 update.J Allergy Clin Immunol2005;115:34–46.
7. Geha RS, Jabara HH, Brodeur SR.The regulation of immunoglobulin E class-switch recombination.Nat Rev Immunol2003;3:721–732.
8. Hamelmann E, Cieslewicz G, Schwarze J, Ishizuka T, Joetham A, Heusser C, Gelfand EW.Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness.Am J Respir Crit Care Med1999;160:934–941.
10. Masoli M, Weatherall M, Holt S, Beasley R.Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma.Thorax2005;60:730–734.
11. Montuschi P, Sala A, Dahlén SE, Folco G.Pharmacological modulation of the leukotriene pathway in allergic airway disease.Drug Discov Today2007;12:404–412.
12. Storms W, Chervinsky P, Ghannam AF, Bird S, Hustad CM, Edelman JM.A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge.Respir Med2004;98:1051–1062.
13. Holgate S, Buhl R, Bousquet J, Smith N, Panahloo Z, Jimenez P.The use of omalizumab in the treatment of severe allergic asthma: a clinical experience update.Respir Med2009;103:1098–1113.
14. Hall IP.Pharmacogenetics of asthma.Chest2006;130:1873–1878.
15. Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ.Use of regularly scheduled albuterol treatment in asthma: genotype stratified, randomised, placebo-controlled cross-over trial.Lancet2004;364:1505–1512.
16. Fanta CH.Asthma.N Engl J Med2009;360:1002–1014.
17. Joos S, Musselmann B, Miksch A, Rosemann T, Szecenyi J.The role of complementary and alternative medicine (CAM) in Germany – a focus group study of GPs.BMC Health Serv Res2008;8:127.
18. Han JS.Acupuncture and endorphins.Neurosci Lett2004;361:258–261.
19. Stux G, Berman B, Pomeranz B.Basics of acupuncture2003.London, UK:Springer.
20. Zijlstra FJ, van den Berg-de Lange I, Huygen FJPM, Klein J.Anti-inflammatory actions of acupuncture and mediators of inflammation.Mediators Inflamm2003;12:59–69.
21. Chu KA, Wu YC, Ting YM, Wang HC, Lu JY.Acupuncture therapy results in immediate bronchodilating effect in asthma patients.J Chin Med Assoc2007;70:265–268.
22. Ahrens B, Gruber C, Rha RD, Freund T, Quarcoo D, Awagyan A.BCG priming of dendritic cells enhances T regulatory and Th1 function and suppresses allergen-induced Th2 function in vitro and in vivo.Int Arch Allergy Immunol2009;150:210–220.
23. Neveu WA, Allard JL, Raymond DM, Bourassa LM, Burns SM, Bunn JY, et al..Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function.Respiratory Research2010;11:28.
24. Jeong HJ, Kim BS, Kim KS, Kim HM.Regulatory effect of cytokine production in asthma patients by SOOJI CHIM (Koryo hand acupuncture therapy).Immunopharmacol Immunotoxicol2002;24:265–274.
25. Petti FB, Liguori A, Ippoliti F.Study on cytokines IL-2, IL-6, IL-10 in patients of chronic allergic rhinitis treated with acupuncture.J Tradit Chin Med2002;22:104–111.
26. Barton BE.Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes.Expert Opin Ther Targets2005;9:737–752.