The new england journal of medicine

p er s pect ive

Allergen Avoidance in the Treatment

of Asthma and Rhinitis
Thomas A.E. Platts-Mills, M.D., Ph.D.

The evidence that allergens found inside houses care to point out, their study does not show or im-
are an important cause of perennial rhinitis and ply that allergen avoidance should not be recom-
asthma comes from three types of studies. In one mended for patients with asthma who are allergic
type, the delivery of allergen in the laboratory has to dust mites. What their study shows very clearly is
provoked the clinical condition; in another type, the that distributing or recommending allergen-proof
avoidance of allergens has been shown to result in covers in a family-practice setting is unlikely to be
fewer symptoms of disease; and the third type ex- effective as a single measure in the absence of a com-
amines the epidemiologic association between the prehensive avoidance strategy. The obvious implica-
prevalence of disease and sensitization to particular tion of these studies is that mattress covers as a rou-
allergens. These results lead logically to two differ-
ent forms of allergen-specific treatment: immuno-
therapy, in which the physician tries to induce tol- Genetically
erance to a given allergen, and avoidance of allergen. Predisposed
Population
In a world in which medical management is Exposure to allergens
dominated by pharmacologic treatment, it is impor- Mite
tant to have other options for both patients and phy- Cat
Cockroach Primary avoidance
sicians; allergen avoidance is such an option. The Alternaria Endotoxin
Diesel or other High-dose cat allergen
case for the avoidance of dust-mite allergen as a particulates
treatment for asthma comes from controlled trials
in patients’ homes and from experiments in which Sensitization
(Th2, IgE, IgG1, IgG4)
patients were transferred to a sanatorium or an “al-
lergen-free” hospital room. In those studies, the pa- Allergens
tients had impressive decreases in the severity and Diesel particulates
Endotoxin
frequency of symptoms, medication requirements, Rhinovirus Allergen avoidance
and in nonspecific bronchial hyperreactivity (see Inhaled corticosteroids

Figure).
The authors of the two negative reports in this Inflammation or
issue of the Journal hoped that they would be able to Bronchial Hyperreactivity
(T cells, mast cells, eosinophils)
show that the placement of impermeable covers on
patients’ mattresses would provide significant ben-
Allergens
efit for patients with perennial rhinitis (Terreehorst Rhinovirus
et al. [pages 237–246] or asthma (Woodcock et al. Endotoxin
Allergen avoidance
[pages 225–236]). These were both well-conducted
studies in which the investigators and the patients
were, to the extent that it was possible, blinded to Nasal Symptoms
the treatment-group assignment. Furthermore, be- or Wheezing
cause the investigators did not know which subjects
were allergic to dust mites, they could not have Allergen Avoidance as a Treatment for Perennial Rhinitis and Asthma.
known which patients “should have” had improve- Th2 denotes type 2 helper T cells.
ment. As Woodcock and his colleagues take great

n engl j med 349;3 www.nejm.org july 17, 2003 207

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 The new england journal
tine part of the treatment of asthma are not worth
the price. However, according to other studies, the
correct conclusion is that treatment by means of al-
lergen avoidance requires the definition of what pa-
tients are allergic to, additional measures beyond
the use of mattress covers, and education.
Many controlled trials are plagued by placebo ef-
fects, but such effects are particularly problematic
in any study that attempts to change a patient’s life-
style. Delivery of a mattress cover to the family clear-
ly indicates what the study is about, and the family
will generally assume that they should do other
things to “help.” Even if the family members do not
know whether they are in the active-intervention
group or the control group, they do know that they
are in an allergen-avoidance study. Some research-
ers have gone so far as to argue that an observation-
al group is needed in which no home visit is con-
ducted and no mention of a home intervention is
made until the end of the study. Thus, this type of
study can have two kinds of errors: either the in-
tervention is inadequate to achieve a clinically sig-
nificant decrease in exposure to allergens, or the
families have made other changes, intentionally or
unintentionally, that have a greater effect than the
intervention being studied.
Dust mites are not the only agent that can influ-
ence lung function. The home environment, apart
from the mattress, is an important source of non-
specific irritants as well as other allergens. For ex-
ample, endotoxin and cat allergen have been dem-
onstrated to affect nasal and bronchial symptoms,
and equally important, each of them can be meas-
ured in floor dust and is airborne. There is now evi-
dence that each of these agents has a complex role
in allergic disease. Endotoxin, which is a potent irri-
tant to the respiratory tract, can help to suppress
sensitization if exposure occurs early in life. There is
increasing evidence that children raised in a house-
hold with a cat are less likely to become sensitized
208 n engl j med 349;3 www.nejm.org
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of medicine
to cat allergen and that very high levels of exposure
induce a specific form of immunologic tolerance.
By contrast, moderate exposure to cat allergen is
sufficient to induce sensitization in a large number
of children who have never lived in a household with
a cat. These paradoxical findings make it difficult to
interpret the results of studies on secondary and
particularly primary avoidance (see Figure).
The alternative implication of the current stud-
ies is that we do not understand what is necessary
to make patients with asthma well, let alone to cure
the disease. The currently available pharmaceuti-
cal treatments control asthma, but they do not pro-
vide effects that last for more than one month af-
ter treatment is discontinued. Is it possible that we
have missed an element of the experiments in sana-
toriums or allergen-free rooms? The conditions in
those studies almost certainly included decreased
exposure to animal dander, endotoxin, and fungal
spores, as well as the decrease in levels of mite al-
lergen. Alternatively, those regimens may have in-
cluded other changes such as increased physical ac-
tivity, which is usually possible once symptoms have
improved, but which is not part of routine treatment.
What is clear is that some changes in diet, life-
style, cleanliness, or housing have led to a massive
increase in the prevalence and severity of asthma.
The challenge is both to identify the changes that
are responsible for this increase and to design a
treatment approach that makes it possible to pre-
vent or cure the disease. Physicians are very good at
prescribing drugs and very poor at effecting chang-
es in behavior, even when the latter are better for the
patient. If minor reductions in exposure to allergen
are not sufficient, we need either to persuade fami-
lies to change their living conditions on a large scale
or to identify the real cause of the increase in the
prevalence of asthma.
From the University of Virginia Asthma and Allergic Disease Cen-
ter, Charlottesville.
july 17, 2003