What GP leadership is all about
In this new series, specialists detail the latest developments in their field. This week, Dr Glenis Scadding outlines how effective new treatments can improve rhinitis and resultant asthma
Upper and lower respiratory tracts are now regarded as 'united airways'. This comes from the similar epidemiology and pathophysiology of rhinitis and asthma. Also, rhinitis gives a three-fold relative risk for the subsequent development of asthma and can also cause bronchial hyper-reactivity. Similar trigger factors such as allergies and viruses, often acting initially in the upper respiratory tract, can cause exacerbations in both areas.
Three recent papers suggested treatment of rhinitis benefits asthma. There are also large retrospective US studies showing a topical inhaled steroid one nasal spray prescription a year reduces the risk of an emergency visit for asthma from 1 down to 0.7. The risk is halved with three or more sprays1.
Antihistamines alone do not reduce the risk very substantially, but when combined with a topical steroid emergency visits and hospitalisation are reduced by an impressive two-thirds2,3.
Since more than 80 per cent of asthmatics also have rhinitis it makes sense for them to be asked about upper respiratory symptoms of blockage, running, itching and discharge (both anterior and posterior), and for these symptoms to be treated according to WHO's Allergic Rhinitis and its Impact on Asthma guidelines4.
This should prove a cost-effective treatment since emergency visits and hospitalisation account for the major part of asthma expenditure.
This is a monoclonal antibody developed against IgE, which is, of course, the allergy antibody. The resulting preparation reduces serum IgE levels and decreases IgE mediated mast cell degranulation which is the start of the allergic response. It has proved effective in both asthma and rhinitis, and also in severe peanut allergy. But it is likely to prove an expensive therapy and so will initially be used only on patients with severe disease which is demonstrably IgE mediated. It needs to be given by injection, a factor that will also restrict its use, but the systemic nature of this treatment means it should be effective in patients with multi-allergic problems5. It is currently licensed in the US, but not the UK.
Anti-leukotrienes for rhinitis
The leukotriene receptor antagonists (LTRAs), montelukast and zafirlukast, have been available for asthma treatment for some time. More recent studies have demonstrated efficacy in rhinitis and these drugs have subsequently become licensed in the US for this condition.
In seasonal allergic rhinitis the LTRAs are no more effective than antihistamines and, even if combined with an antihistamine, are no more effective than an intranasal steroid. But in more severe rhinosinusitis associated with nasal polyps open trials have shown a degree of benefit in two-thirds of patients. A recent double-blind study in nasal polyposis has also proven their effectiveness6.
Medical treatment avoids surgery in chronic rhinosinusitis
A recent prospective randomised study7 demonstrated that medical therapy was as effective as surgery. Patients were treated with topical and, in some cases, brief oral steroids, nasal douching and three months of low-dose erythromycin and subsequently monitored over the course of one year. Medical treatment was found to be as effective in patients with nasal polyps and those with non-polypoid rhinosinusitis.
In polyposis, medical treatment was superior in its effects on improving concomitant asthma.
Many patients with significant allergic disease are not completely controlled by pharmacotherapy and so alternative methods of immunotherapy are being sought. Among these sublingual immunotherapy, where the allergen is taken and held under the tongue for one minute before being swallowed, is effective according to a recent Cochrane meta-analysis8. There is evidence for both symptom reduction and for a decrease in the use of pharmacotherapy. The effects appear more modest than for injection immunotherapy and the treatment is expensive since high doses of allergen are used. Side-effects are local and mild thus only the first dose needs to be given under observation; subsequent daily doses can be taken at home.
A trial of sublingual immunotherapy for grass pollen took place in the UK last year with demonstrable efficacy for the highest dose used. A further study will start here in the autumn allowing several months of immunotherapy to be given before the pollen season starts.
There are a few other studies in progress and we are undertaking a housedust mite sublingual immunotherapy study attempting to use lower doses, but employing lactobacillus as an adjuvant attempting to steer the immune response away from allergy.
As yet, sublingual immunotherapy is not licensed other than on a trial basis, but it will be available for private use shortly.
Guideline-based asthma control
The following one-year Gaining Optimal Asthma Control study established that some form of anti-inflammatory systemic treatment is probably necessary in many asthmatics.
Researchers evaluated the proportion of patients achieving asthma control as specified by the Global Initiative for Asthma/British Guideline on the Management of Asthma. Patients with uncontrolled asthma were stratified before randomisation into:
·those who had never received inhaled steroids (SI),
·those on low-dose inhaled steroids (S2)
·those on moderate-dose inhaled steroids (S3).
They were randomised to Flixotide (FP 100-500mcgs bd) or Seretide (SFC 50/100 to 50/500mcgs bd).
Phase 1: doses were stepped up every
12 weeks until total control was achieved or maximum dose reached.
Phase 2: patients then remained on this dose for the remainder of the double-blind treatment period.
Total control (defined as: normal lung function and no symptoms, rescue medication, night awakenings, exacerbations, emergency visits or adverse events enforcing change in therapy), was assessed over the last week of each 12-week treatment period and at the end of phase 2.
Some 3,421 were randomised.
Results: more patients achieved total control with SFC than with FP in phase 1; S1 42% v 31%, S2 32% v 20%, S3 19% v 8% (all strata common P<.001). of="" these="" patients="" s1="" 69%="" v="" 74%,="" s2="" 69%="" v="" 62%,="" s3="" 69%="" v="" 73%="" were="" also="" controlled="" at="" the="" end="" of="" phase="" 2.="" after="" one="" year="" the="" cumulative="" proportion="" of="" patients="" achieving="" control="" (sfc="" v="" fp)="" was="" s1="" 50%="" v="" 40%,="" s2="" 44%="" v="" 28%,="" s3="" 29%="" v="">
Clinically meaningful improvements in quality-of-life scores were observed for both drugs across all strata with near maximal scores at end point. Exacerbations requiring oral steroids and/or hospitalisations/ emergency visits were low after both treatments, but significantly lower with SFC (p<.009 all="">
Addition of oral steroids to those patients not achieving control resulted in only a
small percentage of additional responders (5-11 per cent).
There was a low incidence of adverse events, but around 8 per cent of patients had 24-hour urinary-free cortisol below the lower limit of normal at week 52.
This study demonstrates that total control was only achieved in 50 per cent of patients in the mildest group using the optimum therapy of inhaled steroid plus long-acting ?-agonist (ICS + LABA). Thus, more than half of patients treated for asthma will have less than total control and this implies there is ongoing inflammation in their airways and presumably ongoing airways remodelling.
At present, there are few available options: anti-leukotrienes are effective in some, but not all, patients; some antihistamines appear to have modest beneficial effects in asthma. There is a very real need for a safe and effective oral therapy that will treat both asthma and rhinitis.
1 Adams HD. The effect of treatment of allergic rhinitis on asthma morbidity, including emergency department visits.
Curr Opin Allergy Clin Immunol. 2003 Feb; 3(1):29-32
2 Crystal-Peters J et al. Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalisations and emergency department visits. J Allergy Clin Immunol. 2002 Jan;109(1):57-62
3 Corren J et al. Rhinitis therapy and the prevention of hospital care for asthma: a case-control study. J Allergy Clin Immunol. 2004 Mar;113(3):415-9
4 Bousquet J et al and the ARIA workshop. Allergic rhinitis and its impact on asthma. J. Allergy Clin Immunol. 2001
5 Louis R. Anti-IgE: a significant breakthrough in the treatment of airway allergic diseases. Allergy. 2004 Jul;59(7):698-700
6 Keith P. A double blind, placebo-controlled study of montelukast in nasal polyposis. Poster presented at WAO, Vancouver, September 2003
7 Ragab SM et al. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Laryngoscope. 2004 May;114(5):923-30
8 Wilson DR et al. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2003;(2):CD002893
www.bsaci.org www.aaai.org www.allergyfoundation.com
Glenis Scadding is a consultant physician in allergy and rhinology at the Royal National Throat, Nose and Ear Hospital, London she also chairs the ENT special interest group for the British Society for Allergy and Clinical Immunology