Objectives. The meta-analysis aims to investigate the efficacy of ectoine nasal spray and eye drops in the treatment of allergic rhinitis and rhinoconjunctivitis symptoms. Design and Methods. This meta-analysis is based on yet unpublished data of four studies. Both nasal and eye symptoms were documented in patient diary cards. All scales were transformed into a 4-point scale: 0 = no, 1 = mild, 2 = moderate, and 3 = severe symptoms. Each symptom was analysed individually in a meta-analysis of the area under the curve values as well as in a meta-analysis of pre- and posttreatment comparison. Results. After seven days of treatment with ectoine nasal spray both nasal and ocular symptoms decreased significantly. A strong reduction of symptom severity was shown for the parameters rhinorrhoea (31.76% reduction) and nasal obstruction (29.94% reduction). Furthermore, the meta-analyses of individual symptoms to investigate the strength of effect after seven days of medication intake showed significant improvement for nasal obstruction, rhinorrhoea, nasal itching, sneezing, itching of eyes, and redness of eyes. The improvement of the symptom nasal obstruction was associated with a strong effect 0.53 (±0.26). Conclusions. The ectoine nasal spray and eye drops seem to be equally effective as guideline-recommended medication in the treatment of rhinoconjunctivitis symptoms. 1. Introduction Allergic rhinitis is clinically defined as an inflammation of the nose with characteristic symptoms such as rhinorrhoea, nasal obstruction, sneezing, and/or itching of the nose. The symptomatic disorder of the nasal mucosa and tissue is associated with an IgE-mediated immune response to allergens and is characterised by two phases: an immediate response after allergen exposure (early phase) and a late phase occurring up to 12 hours later, which predominantly causes nasal congestion [1]. If a concurrent respiratory infection is present, a patient’s probability of developing bronchial asthma as comorbidity increases. Likewise, the risk of developing further allergies with more severe symptoms rises over the time of the disease [2]. A variety of causes for rhinitis exist in both children and adults, but 50% of all cases can be ascribed to allergy [3]. Due to its prevalence, impact on quality of life, impairment of work or school performance, reducing effect on productivity, economic burden, and risk of comorbidities, allergic rhinitis is regarded worldwide as a major chronic respiratory disease. Moreover, it can be associated with significant fatigue, mood changes, cognitive
References
[1]
J. Bousquet, N. Khaltaev, A. A. Cruz et al., “Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen),” Allergy, vol. 63, no. 86, pp. 8–160, 2008.
[2]
C. B？cking, H. Renz, and P. I. Pfefferle, “Pr？valenz und sozio？konomische Bedeutung von Allergien in Deutschland,” Bundesgesundheitsblatt—Gesundheitsforschung—Gesundheitsschutz, vol. 55, no. 3, pp. 303–307, 2012.
[3]
D. P. Skoner, “Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis,” Journal of Allergy and Clinical Immunology, vol. 108, no. 1, supplement, pp. S2–S8, 2001.
[4]
C. Kirmaz, O. Aydemir, P. Bayrak, H. Yuksel, O. Ozenturk, and S. Degirmenci, “Sexual dysfunction in patients with allergic rhinoconjunctivitis,” Annals of Allergy, Asthma and Immunology, vol. 95, no. 6, pp. 525–529, 2005.
[5]
P. S. Marshall, C. O'Hara, and P. Steinberg, “Effects of seasonal allergic rhinitis on fatigue levels and mood,” Psychosomatic Medicine, vol. 64, no. 4, pp. 684–691, 2002.
[6]
B. Kremer, H. M. Den Hartog, and J. Jolles, “Relationship between allergic rhinitis, disturbed cognitive functions and psychological well-being,” Clinical and Experimental Allergy, vol. 32, no. 9, pp. 1310–1315, 2002.
[7]
B. Cuffel, M. Wamboldt, L. Borish, S. Kennedy, and J. Crystal-Peters, “Economic consequences of comorbid depression, anxiety, and allergic rhinitis,” Psychosomatics, vol. 40, no. 6, pp. 491–496, 1999.
[8]
X. Lv, L. Xi, D. Han, and L. Zhang, “Evaluation of the psychological status in seasonal allergic rhinitis patients,” ORL, vol. 72, no. 2, pp. 84–90, 2010.
[9]
E. Angier, J. Willington, G. Scadding, S. Holmes, and S. Walker, “Management of allergic and non-allergic rhinitis: a primary care summary of the BSACI guideline,” Primary Care Respiratory Journal, vol. 19, no. 3, pp. 217–222, 2010.
A. Calderon Moises, P. Rodriguez del Rio, and P. Demoly, “Topical nasal corticosteroids versus oral antihistamines for allergic rhinitis,” Cochrane Database of Systematic Reviews, Article ID CD008232, 2010.
[12]
J. Smiatek, R. K. Harishchandra, O. Rubner, H.-J. Galla, and A. Heuer, “Properties of compatible solutes in aqueous solution,” Biophysical Chemistry, vol. 160, no. 1, pp. 62–68, 2012.
[13]
R. K. Harishchandra, A. K. Sachan, A. Kerth, G. Lentzen, T. Neuhaus, and H.-J. Galla, “Compatible solutes: ectoine and hydroxyectoine improve functional nanostructures in artificial lung surfactants,” Biochimica et Biophysica Acta, vol. 1808, no. 12, pp. 2830–2840, 2011.
[14]
T. Dirschka, “Ectoin—Anwendung und Perspektiven für die Dermatologie,” Aktuelle Dermatologie, vol. 34, no. 4, pp. 115–118, 2008.
[15]
G. Lentzen and T. Schwarz, “Extremolytes: natural compounds from extremophiles for versatile applications,” Applied Microbiology and Biotechnology, vol. 72, no. 4, pp. 623–634, 2006.
[16]
A. Bilstein, “Immuno-protective effects of the extremolyte ectoine in animal models and humans,” in Proceedings of the 28 Congress of the European Academy of Allergy and Clinical Immunology, Warsaw, Poland, 2009.
[17]
U. Sydlik, I. Gallitz, C. Albrecht, J. Abel, J. Krutmann, and K. Unfried, “The compatible solute ectoine protects against nanoparticle-induced neutrophilic lung inflammation,” The American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 1, pp. 29–35, 2009.
[18]
U. Sydlik, H. Peuschel, A. Paunel-Gorgulu, et al., “Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation,” European Respiratory Journal, vol. 41, no. 2, pp. 433–442, 2013.
[19]
A. M. Vestweber, “Das Stressschutzmolekül MedEctoin zeigt positive Ergebnisse bei der Psoriasis und in der topischen Applikation bei Patienten mit trockener, schuppiger Haut,” Naturheilpraxis mit Naturmedizin, pp. 2–7, 2009.
W. Carr, J. Bernstein, P. Lieberman et al., “A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis,” The Journal of Allergy and Clinical Immunology, vol. 129, no. 5, pp. 1282.e10–1289.e10, 2012.
[22]
E. O. Meltzer, T. Shekar, and A. A. Teper, “Mometasone furoate nasal spray for moderate-to-severe nasal congestion in subjects with seasonal allergic rhinitis,” Allergy and Asthma Proceedings, vol. 32, no. 2, pp. 159–167, 2011.
[23]
B. J. Winer, D. R. Brown, and K. M. Michels, Statistical Principles in Experimental Design, vol. 3, McGraw-Hill, New York, NY, USA, 1991.
[24]
C. Clopper and E. Pearson, “The use of confidence or fiducial limits illustrated in the case of the binomial,” Biometrika, vol. 48, no. 3-4, pp. 433–440, 1934.
[25]
J. Higgins and S. Green, “Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0,” The Cochrane Collaboration , 2011, http://handbook.cochrane.org.
[26]
D. F. Stroup, J. A. Berlin, S. C. Morton et al., “Meta-analysis of observational studies in epidemiology: a proposal for reporting,” Journal of the American Medical Association, vol. 283, no. 15, pp. 2008–2012, 2000.
[27]
H. M. Cooper, L. V. Hedges, and J. C. Valentine, The Handbook of Research Synthesis and Meta-Analysis, Russell Sage Foundation, 2009.
[28]
M. Egger, K. Dickersin, and G. D. Smith, “Problems and limitations in conducting systematic reviews,” in Systematic Reviews in Health Care, pp. 43–68, BMJ Publishing Group, 2008.
[29]
D. Sharpe, “Of apples and oranges, file drawers and garbage: why validity issues in meta-analysis will not go away,” Clinical Psychology Review, vol. 17, no. 8, pp. 881–901, 1997.
[30]
C. J. Ferguson, “An effect size primer: a guide for clinicians and researchers,” Professional Psychology: Research and Practice, vol. 40, no. 5, pp. 532–538, 2009.
[31]
J. P. T. Higgins, S. G. Thompson, J. J. Deeks, and D. G. Altman, “Measuring inconsistency in meta-analyses,” British Medical Journal, vol. 327, no. 7414, pp. 557–560, 2003.
[32]
F. M. Baroody, K. A. Foster, A. Markaryan, M. DeTineo, and R. M. Naclerio, “Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis,” Annals of Allergy, Asthma and Immunology, vol. 100, no. 3, pp. 194–199, 2008.
[33]
A. Eichel, J. Wittig, K. Shah-Hosseini, et al., “A prospective, controlled study of SNS01 (ectoine nasal spray) compared to BNO-101 (phytotherapeutic dragees) in patients with acute rhinosinusitis,” Current Medical Research and Opinion, vol. 29, no. 7, pp. 739–746, 2013.
[34]
A. Marini, K. Reinelt, J. Krutmann, et al., “Ectoine-containing cream in the treatment of mild to moderate atopic dermatitis: a randomised, comparator-controlled, intra-individual double-blind, multi-center trial,” Skin Pharmacology and Physiology, vol. 27, no. 2, pp. 57–65, 2014.
[35]
D. P. Skoner, G. S. Rachelefsky, E. O. Meltzer et al., “Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate,” Pediatrics, vol. 105, no. 2, p. E23, 2000.
[36]
E. Johnson, A. Brookhart, and J. Myers, “Study size planning,” in Developing a Protocol for Observational Comparative Effectiveness Research: A User's Guide, P. Velentgas, N. A. Dreyer, P. Nourjah, et al., Eds., Agency for Healthcare Research and Quality, AHRQ, Rockville, Md, USA, 2013.
[37]
M. D. A. Carlson and R. S. Morrison, “Study design, precision, and validity in observational studies,” Journal of Palliative Medicine, vol. 12, no. 1, pp. 77–82, 2009.
