One airway, one disease: exploring the link between rhinitis and asthma
Asthma and allergic rhinitis (AR) are linked on several levels (Table 1). These diseases have a high co-incidence rate,(1) share a common anatomy(1-3) and similar responsiveness triggers. Both are characterized by Th 2 inflammatory processes involving multiple (and common) inflammatory cells and mediators(1;2) which manifest with different symptoms depending upon airway location. In the nose they cause itching, sneezing, rhinorrhoea and congestion, whereas in the lung they are associated with bronchoconstriction, wheezing and smooth muscle contraction.(1) Allergen provocation tests have yielded further evidence of the link in the form of naso-bronchial cross-talk: with nasal allergen challenge leading to an inflammatory response in the lower airways,(4) and vice versa.(5) More convincing is the fact that poor rhinitis control predicts poor asthma control.(6) Finally, rhinitis often precedes the development of asthma, and is one of the strongest independent risk factors for the onset and incidence of asthma.(7) As these diseases are so intrinsically linked, they should be optimally treated together.
The upper airway should be managed with the most effective AR treatment which should improve asthma outcomes and possibly prevent progression of rhinitis to asthma. The lower airway should also be treated with guideline-directed care (i.e. step-up/step-down approach) with special consideration given to choosing an inhalation device which is easy to use and provides targeted and assured drug delivery to the lungs.
[Dr Glenis Scadding, UK]
The link between AR and allergic asthma is undisputed, representing a continuum of the same disease. The nose and the lungs are connected anatomically and pathophysiologically, and ‘talk’ to each other. Therefore, patients with allergic asthma should be assessed for rhinitis, and those with rhinitis should be assessed for asthma, and both conditions managed together. For asthma patients, device choice is just as important as drug choice. Many asthma patients unknowingly use their inhaler incorrectly, which results in poor compliance and sub-optimal asthma control. An inhaler device which ensures correct use, like the Novolizer® (a breath-activated dry powder inhaler (DPI)) should improve asthma control. It’s also important to effectively treat co-morbid AR since this is associated with more severe asthma, a greater negative impact on patient quality of life, increased use of asthma medication, higher drug costs and an increased number of physician visits and hospitalizations due to asthma.(6;8;9) Asthma burden in later life might be reduced by more effective early treatment of AR. Intranasal corticosteroids (INS) are currently considered the most effective drug class for the symptomatic treatment of AR. However, recently their effect on AR symptom relief has been significantly and comprehensively exceed by Dymista®, a new class of AR medication (WHO code ATC R01AD58). It is, therefore, expected that Dymista® will not only provide better control of AR but might also improve asthma outcomes in co-morbid patients.
[Prof J Christian Virchow, Germany]
Dymista® incorporates azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation, delivered in a single device. Dymista® (Meda AB, Solna, Sweden) is indicated for the relief of symptoms of moderate/severe seasonal AR (SAR) and perennial AR (PAR) if monotherapy with either intranasal antihistamines or INS is not considered sufficient.(10)
Better allergic rhinitis treatment, better asthma control?
Given the relationship between AR and asthma, it appears likely that reducing inflammation in the upper airway will improve outcomes in the lower airway for co-morbid patients. However, as all AR treatments are NOT equally effective in controlling rhinitis symptoms, they are also NOT equally effective in improving asthma outcomes in comorbid patients. For example, INS provide better AR symptom control than oral anti-histamines.(11) Consequently INS (but not oral anti-histamines) have a positive impact on many asthma outcomes, such as improved pulmonary function and reduced asthma rescue medication use.(12;13) However, INS monotherapy, and even multiple therapies, provide sub-optimal symptom relief for many AR patients with moderate/severe disease.(14) More effective AR treatments than INS are needed to improve rhinitis control, which should in turn have a greater positive impact on co-morbid asthma control. Dymista® has shown consistent superiority over INS in the largest direct head-to-head clinical development programme in AR to date.(15-17) It provides twice the nasal and ocular symptom relief of an INS (Figure 1) and is well-tolerated.(18) Dymista® patients also experienced faster and more complete control than FP; 1 in 2 Dymista® patients halved their nasal symptom burden, with 1 in 4 patients shifting from moderate/severe to mild symptom severity or less after 14 days, and up to about a week faster than FP.(15) The results in real life have been even better, with 1 in 2 Dymista®-patients perceiving their disease to be ‘well controlled’ after just 3 days of treatment (Figure 2).(19)
[Dr Warner Carr, USA]
According to Allergic Rhinitis and its Impact on Asthma (ARIA) rhinitis and allergic asthma should be treated together using a single approach if possible,(20) since more effective control of one leads to more effective control of the other. A clear treatment hierarchy exists in AR: Dymista® > INS > oral anti-histamines which is effectively mirrored for allergic asthma outcomes in co-morbid patients with AR. Considering that Dymista® provides twice the symptom relief as INS, faster more complete symptom control and without an efficacy threshold, it could be assumed that Dymista® may be more effective than INS in improving co-morbid asthma outcomes. This will have important socioeconomic consequences, with Dymista® not only reducing direct (e.g. multiple medication costs) and indirect (e.g. GP visits) AR costs, but also with the potential to reduce asthma medication use, exacerbations and hospitalizations. In my opinion Dymista® should be considered the drug of choice for the treatment of moderate/severe AR patients, since INS (and multiple therapies) provide insufficient symptom relief for many of them. Furthermore, Dymista® should be considered first line for AR patients with an asthma comorbidity.
[Prof Magnus Wickman, Sweden]
Advances in asthma treatment: a two way street
Effective asthma management can also improve AR outcomes.(21) GINA recommend a 5-step flexible approach to treatment, with reliever medication recommended at each step for quick relief of symptoms, inhaled corticosteroids (ICS) for step 2 and above, with ICS dose increases or addition of long-acting β2-agonist (LABA) recommended for step-up therapy.(22) Guidelinedirected care, therefore, requires a flexible approach, with the ability to increase and decrease ICS dose and add-on or remove therapies as appropriate. The choice of inhaler device is, therefore, crucial. The same device should be suited to regular reliever therapy provision, flexible ICS monotherapy and step up to LABA add-on as required. It should also be easy to use, deliver sufficient corticosteroid to the lungs and promote good compliance. The Novolizer® (Meda, Solna, Sweden) is a multi-dose, refillable, breath-actuated DPI which delivers salbutamol, budesonide or formoterol.(23) It incorporates multiple control feedback mechanisms (i.e. optical, acoustic and sensory signals). These guide patients through a successful inhalation manoeuvre (Figure 3).(23) The Novolizer® is also forgiving of poor patient technique as drug particle size generated through it is relatively independent of patients’ flow rate(23). Patients cannot avoid inhaling correctly through the Novolizer®, and receive reassurance of high lung deposition and at the right particle size to reach the small airways (Figure 4).(24) All of these features ensure that use of the Novolizer® is associated with improved asthma control and that most patients prefer it to previously used inhaler devices.(25)
[Dr William Berger, USA]
It is essential that we provide the best available AR and asthma treatments, in order to provide optimal control of both diseases. For AR, Dymista® is undisputedly the most effective symptomatic treatment option. For asthma, inhaler choice is just as important as drug choice. The Novolizer® is a technically advanced DPI, delivering an ICS for maintenance therapy, a short-acting β2-agonist for as-needed treatment or a long-acting β2-agonist to treat nocturnal symptoms or more severe asthma in combination with an ICS. This free combination strategy is in keeping with guideline-directed step-approach to treatment, providing tailor-made therapy for all grades of asthma. The Novolizer® is an ideal inhaler for patients who want a DPI and a guide through the inhalation manoeuvre. Its many novel features ensure that it is easy to use correctly and inhale through, making it suitable for all patients regardless of disease severity, in the elderly and for children. Its assured drug delivery and high drug deposition improve compliance and lung function and other asthma outcomes and may also improve rhinitis control in co-morbid patients. Dymista® is a perfect choice for our AR patients with moderate/severe disease. For our co-morbid patients it is the most effective AR product, providing the highest efficacy in upper airway control and the potential to improve lower airway control too. Let’s treat these diseases together and give our patients the best chance of disease control.
[Prof Philippe Stock, Germany]
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- Braunstahl GJ, Overbeek SE, Kleinjan A, Prins JB, Hoogsteden HC, Fokkens WJ. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. J Allergy Clin Immunol 2001; 107(3):469-76.
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- Shaaban R, Zureik M, Soussan D, Neukirch C, Heinrich J, Sunyer J et al. Rhinitis and onset of asthma: a longitudinal populationbased study. Lancet 2008; 372(9643):1049-57.
- Magnan A, Meunier JP, Saugnac C, Gasteau J, Neukirch F. Frequency and impact of allergic rhinitis in asthma patients in everyday general medical practice: a French observational cross-sectional study. Allergy 2008; 63(3):292-8.
- Thomas M, Kocevar VS, Zhang Q, Yin DD, Price D. Asthmarelated health care resource use among asthmatic children with and without concomitant allergic rhinitis. Pediatrics 2005; 115(1):129-34.
- Dymista summary of product characteristics. https://www.medicines.org.uk/emc/medicine/27579 . 2014.
- Bender BG, Milgrom H. Comparison of the effects of fluticasone propionate aqueous nasal spray and loratadine on daytime alertness and performance in children with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2004; 92(3):344-9.
- Price D, Kemp L, Sims E, von ZJ, Navaratnam P, Lee AJ et al. Observational study comparing intranasal mometasone furoate with oral antihistamines for rhinitis and asthma. Prim Care Respir J 2010; 19(3):266-73.
- Lohia S, Schlosser RJ, Soler ZM. Impact of intranasal corticosteroids on asthma outcomes in allergic rhinitis: a meta-analysis. Allergy 2013; 68(5):569-79.
- Price D, Bousquet J, Pitman R, Lieberman P, Munzel U, Meltzer E. Sub-optimal control of allergic rhinitis: the need for a new and more effective treatment option. Allergy 68[Suppl 97], A405. 2013.
- Meltzer E, Ratner P, Bachert C, Carr W, Berger W, Canonica GW et al. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol 2013; 161(4):369-77.
- Carr W, Bernstein J, Lieberman P, Meltzer E, Bachert C, Price D et al. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol 2012; 129(5):1282-9.
- Price D, Shah S, Bhatia S, Bachert C, Berger W, Bousquet J et al. A new therapy (MP29-02) is effective for the long-term treatment of chronic rhinitis. J Investig Allergol Clin Immunol 2013; 23(7):495-503.
- Berger WE, Shah S, Lieberman P, Hadley J, Price D, Munzel U et al. Long-term, randomized safety study of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) in subjects with chronic rhinitis. J Allergy Clin Immunol Pract 2014; 2(2):179-85.
- Klimek K, Bachert C, Mösges R, Munzel U, Price D, Virchow JC, Wahn U, Bousquet J. Effectiveness of MP29-02 for the treatment of allergic rhinitis in real-life: results from a noninterventional study. Allergy Asthma Proc. 2015;36:40-47.
- Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008; 63 Suppl 86:8-160.
- Stelmach R, do Patrocinio TN, Ribeiro M, Cukier A. Effect of treating allergic rhinitis with corticosteroids in patients with mild-to-moderate persistent asthma. Chest 2005; 128(5):3140-7.
- GINA Guidelines. http://www.ginasthma.org/GINA-Report
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- Moeller M, Grimmbacher S, Munzel U. Improvement of asthma therapy by a novel formoterol multidose dry powder inhaler. Arzneimittelforschung 2008; 58(4):168-73.
- Scadding G, Walker S. Poor asthma control?–then look up the nose. The importance of co-morbid rhinitis in patients with asthma. Prim Care Respir J 2012; 21(2):222-8.