Abstract
Summary:
Many factors can impair asthma control. One which is frequently overlooked is rhinitis. Asthma patients with significant rhinitis are over four times more likely to have poorly controlled asthma than those without. Over 80% of patients with asthma have rhinitis, which may be allergic or inflammatory/non-allergic. Both types of rhinitis share pathophysiological similarities with eosinophilic asthma, cause bronchial hyper-reactivity, and are predisposing factors for the subsequent development of asthma. Nasal allergen challenge in allergic rhinitis results in inflammation in the bronchi as well as the nose, and the reverse is also true. This article reviews briefly the evidence for the link between asthma and rhinitis, advocates looking for rhinitis when patients present with poorly controlled asthma, and provides guidance for the diagnosis and treatment of rhinitis.
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Introduction: the difference between asthma severity and asthma control
boxed-textNational and international asthma treatment guidelines have previously focused on the assessment and classification of the severity of symptoms.1–4 Evidence now suggests that asthma severity is a variable feature of a patient's condition and may fluctuate over months or years,5,6 possibly leading to underestimation of severity, inadequate therapy and increased morbidity. Findings from studies of discordance between asthma severity and symptoms/lung function, and between severity, inhaled corticosteroid (ICS) and reliever medication use,7 suggest that classification and treatment of asthma based on severity alone is inappropriate.
In view of these considerations, and the demonstration in several studies that asthma control was achievable in most patients,8–13 the Global Initiative for Asthma (GINA) guidelines currently recommend treatment based on achieving and maintaining asthma control.1 This is defined as “the extent to which the manifestations of asthma have been reduced or removed by treatment” based on assessment of the dual components of current clinical control (e.g. symptoms, limitation of activities/ quality of life (QoL), reliever/rescue treatment use, and lung function) as well as future risk (e.g. exacerbations, decline in lung function, and side effects of treatment).14,15
The role of rhinitis in poor asthma control
Although guideline-defined asthma control is achievable in the majority of patients under strict clinical trial conditions, in real life many patients with asthma continue to have symptoms and poor asthma control.1,16 The major reasons for this are summarised in Table 1.17,18 It is beyond the scope of this article to discuss in detail the evidence for each factor associated with inadequate asthma control. However, rhinitis is a common co-morbidity in many patients with asthma, and the role of uncontrolled rhinitis as a major contributory factor for poor asthma control has recently been highlighted in several studies.19–21 A survey in UK general practice recently showed that asthma patients with significant rhinitis were 4–5 times more likely to have poorly controlled asthma compared to patients without rhinitis, with an odds ratio greater than that for poor compliance with asthma therapy.19 Similarly, a survey of asthma outpatients indicated that chronic rhinitis was the most important risk factor associated with emergency room visits due to asthma exacerbations.20
Making the diagnosis of rhinitis
The cardinal symptoms of rhinitis are rhinorrhoea (nasal discharge), nasal obstruction, itching and sneezing. The diagnosis of rhinitis can be confirmed by following a few simple steps.22 Useful diagnostic questionnaires are available at www.whiar.org.23
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Taking a specific history. Rhinitis can broadly be divided into three categories; allergic, infective and non-allergic.
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Sneezing, itchy nose and palate are likely signs of allergic rhinitis (AR).
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Ask if the symptoms are intermittent or persistent according to the evidence-based World Health Organization (WHO)-sponsored Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines;23 (see Figure 1 for guidance to subsequent tests and treatment).
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Rhinorrhoea can be due to allergen, viral/bacterial infections, alcohol, medications, malignancies, etc. Rarely, isolated rhinorrhoea can be a CSF leak.
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Nasal obstruction/blockage in alternating nostrils is a normal manifestation of rhinitis; bilateral blockage can occur with severe rhinitis, but is more common with nasal polyps.
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Unilateral symptoms are unlikely to be due to allergy, and referral to an ENT surgeon is wise.
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Bilateral itchy, red, swollen eyes are usually associated with AR.
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Taking a family and social history. A family history of any allergic disease (e.g. summer hay fever) makes a diagnosis of AR and asthma more likely. Symptoms on exposure to relevant triggers such as pets, mould, occupational allergens, etc. gives further indication of the probable cause of rhinitis.
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Physical examination. Observe the patient for reduced nasal airflow, mouth breathing, a horizontal nasal crease across the dorsum of the nose, and differences in contour of the nasal bridge. Examine for polyps, crusting, a perforated septum, or mucosal congestion, all of which can indicate persistent rhinitis.
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Routine tests. Blood tests help to exclude other conditions as well as confirm some causes of rhinitis (e.g. thyroid function tests for nasal obstruction). Skin prick tests or serum specific immunoglobulin E (sIgE) tests can be useful to confirm sensitivity to avoidable triggers and are vital when considering avoidance regimes or allergen-specific treatments such as immunotherapy. Allergy tests are not diagnostic when considered independently of the clinical history and should not be used as a tool to ‘screen’ for allergic triggers.
What is the evidence for a link between rhinitis and asthma?
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Epidemiological and pathophysiological studies have consistently indicated that rhinitis and asthma frequently co-exist21,24–49 (see Table 2 ).
Epidemiological studies have demonstrated that approximately 20–60% of patients with rhinitis have clinical asthma, while >80% of patients with allergic asthma have concomitant rhinitis symptoms.24–26 Based on the ARIA classification,23 about one-third of all AR patients have persistent symptoms.27
Pathophysiological studies have provided compelling evidence for both anatomical and physiological similarities between the nose and the bronchi,28–30 as well as there being common agents which can trigger both asthma and rhinitis exacerbations and lead to similar inflammatory responses.29,31,32 Indeed, evidence from some studies suggests that in 20–30% of patients with chronic allergic airway disease, allergen challenge in the upper airways results in significantly reduced lung function33 and increased bronchial responsiveness to methacholine.33,34 Furthermore, allergen challenge in the nasal or bronchial airways leads to marked inflammatory responses in the lower35,36 or upper airways.37,38 Recently, it has been suggested that systemic inflammation triggered by both the adaptive and innate immune system may be the major factor involved in initiating and perpetuating inflammation in combined airway diseases.39
Studies directly investigating the impact of AR on the incidence of asthma have further indicated that worsening AR negatively affects the course of asthma.19,21,40 One cross-sectional survey of over 4400 asthmatic patients recruited from 85 general practices in the UK indicated that the odds of having poor asthma control were more than doubled among patients with mild rhinitis and more than quadrupled among patients with severe rhinitis, compared to patients with no rhinitis.19
Studies investigating the effects of intranasal corticosteroids (INS) on asthma symptoms in subjects with co-morbid AR and asthma have reported conflicting results with regard to the benefits on asthma symptoms.41 Moreover, a meta-analysis of studies assessing the efficacy of INS failed to show a significant effect on asthma outcomes.42 A more recent study, however, has indicated that mometasone furoate nasal spray, a minimally bioavailable nasal corticosteroid, improved the quality of life (QoL) and the burden of respiratory symptoms in patients with persistent AR and asthma.43
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Rhinitis often precedes the development of asthma and is one of the strongest independent risk factors for the onset and incidence of asthma (see Figure 2 ).44
A considerable body of evidence suggests that AR is one of the strongest independent risk factors for asthma.44–49 Population-based longitudinal studies have demonstrated that childhood AR is associated with a significantly increased risk of incident asthma during pre-adolescence, middle age or adult life;47 whereas AR with sensitisation to mite44 and pet allergens and smoking48 is associated with an increased risk of onset of asthma.
Asthma and rhinitis as co-morbid conditions
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a
What are the implications for primary care physicians?
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The presence of co-morbid rhinitis and asthma in the majority of patients with asthma may result in logistic, financial, diagnostic and management challenges for primary care. The logistic challenges are likely to be associated with more asthma-related GP visits and hospital referrals, with associated higher costs.50,51 Diagnostic and patient-management challenges, however, are less clear.
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Diagnosis of co-morbid rhinitis and asthma
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Current guidelines recommend that people with asthma are assessed for rhinitis, and vice versa, so that their symptoms can be managed optimally. 23
This is important because, irrespective of the level of asthma control, patients with rhinitis symptoms have significantly worse health-related QoL compared to patients without, or with a low level of, rhinitis symptoms.52
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Co-existence of rhinitis and asthma may not be recognised by the patient or the clinician.
Some patients do not perceive rhinitis symptoms as impairing their social life, school and work, and therefore do not complain or seek medical advice.23 Furthermore, it is important to distinguish between allergic and non-allergic symptoms as well as between persistent and/or moderate symptoms,23 since this may influence choice of pharmacotherapy. The diagnosis of asthma is also technically more complicated and it may be confused by the presence of cough caused by rhinitis and postnasal drip leading to either inaccurate diagnosis or assessment of asthma severity.53
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Management of patients with co-morbid rhinitis and asthma
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Increasing evidence suggests that better management of rhinitis may result in decreased asthma morbidity.
Unlike the individual treatment strategies for rhinitis and asthma which are well established, the strategy and optimal therapeutic options for the treatment of co-morbid asthma and rhinitis are currently unclear — i.e. should each condition be treated individually or concurrently, and which therapy option should be employed? Current treatment options for asthma and rhinitis are similar and well documented, and include tertiary prevention (preventive strategies for management of established rhinitis and asthma), pharmacological treatments, and immunotherapy.23,54–56 Moreover, a review of studies investigating the efficacy of commonly employed pharmacological treatments of rhinitis on asthma outcomes has indicated that intranasal glucocorticosteroids, antihistamines, anti-leukotrienes and immunotherapy all have the potential to improve both rhinitis and asthma outcomes in patients with both conditions.55
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Guidelines indicate that pharmacological agents traditionally used for treatment of rhinitis may reduce asthma morbidity and thus they recommend a combined treatment strategy for the upper and lower airways for better efficacy:safety ratio. 23
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How should you treat and monitor rhinitis in patients with poor asthma control?
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Current rhinitis management guidelines recommend treatment according to an algorithm based on symptoms and severity (see Figure 3 ).22
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Oral/topical non-sedating antihistamines, and topical INS are the first-line medications of choice for mild and moderate/severe nasal symptoms, respectively. Cromone and antihistamine-containing eye drops can be used alone or in combination with the oral/topical non-sedating antihistamines and INS for ocular symptoms.
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Special care should be taken in pregnancy and young children, particularly with use of decongestants.
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Compliance with treatment should be monitored regularly until patients reach a level of optimal symptom control
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To encourage compliance, all treatment options should be explained to patients and parents of children with rhinitis
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The correct technique for use of nasal sprays should be demonstrated to all patients (see Figure 4)56 in order to optimise benefit and reduce local side effects such as nose bleeds and nasal crusting.56,57
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Conclusions
Substantial epidemiological and pathophysiological evidence indicates that rhinitis and asthma frequently occur as co-morbid conditions in adults and paediatric patients, and that they may be considered as different manifestations of the same inflammatory disease continuum. Rhinitis is a powerful predictor of adult-onset asthma and impacts negatively on the course of more severe asthma, worsening asthma control and impaired QOL as rhinitis severity increases, despite compliance with asthma treatment. Evidence suggests that more aggressive and better treatment of rhinitis is likely to improve asthma outcomes and asthma control, thus emphasising the ARIA-WHO recommendation that patients with asthma and rhinitis should be treated for both conditions. The combination of intranasal corticosteroids for persistent rhinitis and appropriate inhaled asthma therapy should be considered in such patients, with the addition of other drugs including cromones, anti-histamines and leukotriene receptor-antagonists as required. Overall steroid load should be reviewed on a regular basis to prevent unwanted side effects.
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Acknowledgements
Funding Editorial assistance was funded by GSK.
Although not fulfilling the criteria for authorship, the authors gratefully acknowledge the editorial assistance provided by Dr Jagdish Devalia of JD Medical and Scientific Communications Limited which was funded by GlaxoSmithKline (GSK).
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Both authors conceived and wrote the first draft with editorial assistance provided by Jagdish Devalia. GS was responsible for the revision changes. Both authors approved the final version and are solely responsible for its content.
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GS declares honoraria for lecturing, chairing meetings, and advising ALK, GSK, Merck, Stallergenes and Uriach, all of whom make treatments for rhinitis. She has received research funding from ALK, GSK and Merck. SW is a full-time employee of Asthma UK, and declares financial support from Boehringer Ingelheim for international conference attendance.
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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 21, 222–228 (2012). https://doi.org/10.4104/pcrj.2012.00035
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DOI: https://doi.org/10.4104/pcrj.2012.00035
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