Cheap? Oh my, yes. HydrOx Mist was wonderfully cheap, but even Mrs. Kaspbrook was willing to admit that it controlled her son's asthma quite well in spite of that fact. It was cheap because it was nothing but a combination of hydrogen and oxygen, with a dash of camphor added to give the mist a faint medicinal taste. In other words, Eddie's asthma medicine was tap water.2
This issue is about allergic rhinitis, sinusitis, and asthma, with emphasis on how the former two are tied with and may exacerbate the latter. This issue is important because we need all the help we can get with asthma. It is the most common chronic disease of children, with death rates and societal costs that are way too high.
There is no question these three conditions are related, as reviewed in this issue There are epidemiologic relationships: the incidences of asthma and allergic rhinitis have risen dramatically during the past 20 or 30 years. Sinusitis is also diagnosed more commonly now, although this may be because we are looking harder for it. These three conditions are linked by their co-occurrence in patients as well. As many as 80% to 90% of children and adolescents with asthma also have nasal symptoms, half of all patients with asthma have radiographic evidence of sinusitis,2 and up to 38% of patients with allergic rhinitis have asthma. A common immunopathologic mechanism also mediates asthma, allergic rhinitis, and, to a great extent, sinusitis.3 This includes type I immediate IgEdependent hypersensitivity and type IVa chronic allergic cellmediated eosinophilic hypersensitivity. An imbalance of ThI and Th2 lymphocytes also plays a role. Sinusitis may involve bacterial infection, but is still connected with the other two in that the edema of allergic rhinitis predisposes to bacterial sinusitis by interfering with sinus drainage, and the sinuses of a patient with asthma often have the same eosinophilic infiltration as his or her lungs.2
A final connection is experimental data suggesting that inflammation of the upper airway, as from allergic rhinitis or sinusitis, increases bronchoconstriction in the lower airway.2 Several mechanisms seem to mediate this. If this is combined with the observations that (1) allergic rhinitis more often precedes the onset of asthma than the other way around; (2) patients with severe allergic rhinitis tend to have more severe asthma than do those with mild allergic rhinitis; and (3) surgical or medical treatment of sinusitis seems to improve asthma,2 it appears that more aggressive treatment of sinusitis and allergic rhinitis can and should be used to improve the care of the patient with asthma.
THE REAL QUESTION
So, the question that has the most clinical relevance is: Should we be treating allergic rhinitis and sinusitis more vigorously man we currently do to decrease exacerbations of asthma and improve pulmonary function? Of course, we would treat respiratory infections that met criteria for sinusitis or severe rhinitis even if they did not exacerbate or predispose to asthma. What we are really talking about is treating sinusitis that does not meet current guidelines for surgical or medical treatment or milder allergic rhinitis. Will treatment of this group prevent or delay the onset of asthma, reduce severity in those who already have asthma, or both? This is tougher to answer.
DO ALLERGIC RHINITIS AND SINUSITIS CAUSE ASTHMA OR MAKE ATTACKS WORSE?
The evidence we have to answer this is confounded by the way these three conditions and their treatments are interrelated. Whenever any two things (eg, allergic rhinitis and asthma) are highly correlated, there are three possible explanations: A can cause B, B can cause A, or something else (C or C+D+E) can cause both A and B. For example, these three conditions may coexist in individuals because all are due to the same underlying allergic mechanism, or because this mechanism causes asthma and allergic rhinitis, and allergic rhinitis causes sinusitis, or because allergic rhinitis causes sinusitis and asthma or some other combination of these factors.
Treatment effects are subject to the same type of confusion. Let us say you find that treating allergic rhinitis or chronic sinusitis, as with immunotherapy or antihistamines, improves asthma. Does this mean that treating the upper airway conditions improved lower airway function? Not necessarily, because these treatments may work on the immune mechanism behind all three conditions and would have improved asthma, irrespective of whether the patient had allergic rhinitis or sinusitis.
Perhaps the biggest confounder of treatment outcomes is placebo effect.4 Immunotherapy (or desensitization) for allergic diseases is almost 100 years old. Its results were at first dramaticmajor improvements were reported. However, when doubleblind, placebo-controlled studies were conducted to eliminate placebo effect, benefits dropped and results were conflicting. It has taken meta-analysis that combines data from the most disciplined randomized, doubleblind, placebo-controlled studies to demonstrate clear benefits in allergic rhinitis. And there is still controversy about whether this treatment is indicated for asthma. Surgical treatment of sinusitis has also been reported to improve asthma, but there are as yet no randomized, controlled, doubleblind studies to eliminate the placebo bias. As you read doubleblind, placebo-controlled studies for treatment of allergic conditions, note that both the treatment and the placebo groups often improve over baseline. The challenge is to find a significant difference between these two, showing that the treatment group improved significantly more than the placebo group.
RISKS VERSUS BENEFITS OF TREATING UPPER AIRWAY CONDITIONS TO REDUCE LOWER RESPIRATORY DISEASE
Asthma is dangerous - life threatening. It is also costly and impacts quality of life. Sinusitis that does not meet treatment criteria and allergic rhinitis are not dangerous, but they are irritating. If there is a reasonable chance that more aggressive treatment of mild sinusitis or allergic rhinitis will improve asthma, shouldn't we do this? There are risks to most of these treatments. Antibiotics for sinusitis increase the development of resistant organisms, surgery (plus anesthesia) for sinusitis may have poor outcomes, immunotherapy often produces local and systemic reactions and anaphylaxis is a real risk, and other pharmacotherapies for nasal allergies have potential side effects. When the cost and hassle of such treatments are added, the answer is even less clear. It is one thing to ask parents or patients whether they want treatment for allergic rhinitis to relieve its symptoms, and another to offer the same treatment to prevent asthma.
There is also the self-interest problem. The high cost of many of these treatments also means income to those of us who do them. Their use without good evidence of effectiveness opens us up to public criticism and leads to questioning of whether we are serving ourselves or our patients. Therefore, it is doubly important to have the medical evidence that extra and aggressive treatment of allergic rhinitis or mild sinusitis is indicated for ameliorating asthma, in terms of cost, risks, and efficacy, before recommending this as a standard practice. In today's climate, practicing evidence-based medicine means fewer questions from payors and more reimbursement for what we do.
There is only one way to answer this question - by large randomized, double-blind, placebo-controlled studies. Cost effectiveness should be evaluated as well. The outcome measure should be the incidence and severity of asthma that includes objective pulmonary function data. Finding that such aggressive treatment can decrease bronchial hyperactivity to histamine or an allergic challenge is suggestive, but not enough to settle this issue. Current studies are promising, as described in this issue. But, as yet, there are too few or they are otherwise insufficient to draw conclusions, and this concept remains controversial.
Yet the idea is tantalizing. We need help with asthma. We need the studies to show us whether aggressive treatment of allergic rhinitis and sinusitis is indicated, at least for difficult-to-control asthma. Each of you can make your own decision after reading the issue.
1. King S. It. New York: Viking Penguin; 1986:233.
2. Corren J, Rachelefsky GS. Interrelationship between sinusitis and asmma. Immunology and Allergy Clinics of North America. 1994;14:171-183.
3. Simons FER Allergic rhinobronchitis: the asthma-allergic rhinitis link. J Allergy Clin Immunol. 1999;104:534540.
4. Butler C, Steptoe A. Placebo responses: an experimental study of psychophysiological processes in asthmatic volunteers. Br J Clin Psychol. 1986;25:173-183.