Page 1270 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1230 Part tEN Prevention and Therapy of Immunological Diseases

significant reduction in symptoms. Combining symptom and not used in routine clinical practice but may be useful for assessing
medication scores is fraught with difficulty. It is almost impossible effectiveness in clinical trials.
to agree on equivalences between different drugs, let alone the The effectiveness of SIT in seasonal allergic rhinitis has been
relative value of one antihistamine tablet versus a day when confirmed in many trials, using grass, ragweed, and birch pollen.
symptoms are moderate rather than mild. Moreover, SIT has been shown to be clinically effective even in
When assessing improvement in asthma, it is important to patients with severe seasonal rhinitis that is resistant to conven-
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remember that the majority of patients with atopic asthma have tional drug therapy. Data regarding the long-term efficacy of
relatively mild disease that is usually easy to control with standard SIT for allergic rhinitis are limited, but formal studies have shown
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doses of conventional antiasthma drugs. Cases of severe asthma that the effects last for at least 3 years after discontinuing therapy.
are relatively few in number, and the role of allergy in driving Longer-term studies are difficult to conduct, but efficacy has
their disease is often less obvious than in mild cases. In mild been shown for up to 10 years in open studies. The benefits of
cases, resting spirometry will usually be close to predicted values, SIT for perennial rhinitis are less well established than for seasonal
so there is little scope for improvement in simple spirometric rhinitis. In part, this reflects the difficulty in determining the
measures, such as forced expiratory volume per second (FEV 1 ). extent to which allergy is responsible for perennial symptoms.
Peak expiratory flow rates (PEFRs) may show improvement after Allergy to house dust mite (HDM) is common, but only about
SIT, especially the early morning values, which are more likely 50% of those with positive skin tests have symptoms. Conversely,
to be reduced below the patient’s best possible value compared there are other causes of perennial rhinitis, including vasomotor
with evening peak flow rates. Objective measures of bronchial instability, infection, aspirin sensitivity, and so on. Nevertheless,
irritability are more useful markers of improvement and a shift clinical trials have shown a definite benefit provided the subjects
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in the concentration of histamine or methacholine needed to are appropriately selected. Clearer evidence of efficacy has been
induce a 20% fall in FEV 1 (PC 20 ) is commonly used. This measure- obtained in rhinitis caused by pet allergy. Several studies have
ment can be quite variable within individuals, so the minimum shown a marked improvement in tolerance of cat exposure after
change that would be clinically significant is a change of at least SIT, confirmed both on challenge tests and simulated natural
one doubling dilution in the group geometrical mean PC 20 . Other exposure. 13
bronchial challenge tests, such as exercise challenge or adenosine As with any therapy, the risks and cost-effectiveness of SIT
inhalation, may provide additional insights into the ability of need to be assessed on a case-by-case basis. Current drug therapy
an antiasthma treatment to prevent acute attacks. Both these for rhinitis can be very effective, but about 60% of patients with
parameters depend indirectly on the PC 20 , so again, it is important seasonal allergic rhinitis report inadequate symptom control,
to consider statistical and biological significance separately. even when taking maximal doses of antihistamines and intranasal
Although these challenge models are useful surrogates for glucocorticoids. Others experience nose bleeds caused by intra-
evaluating antiasthma treatment, more weight should be placed nasal steroids and drowsiness caused by antihistamines. Moreover,
on improvements in the symptoms or progression of the disease we are now more aware of the adverse effects of rhinitis on
than on protection against laboratory challenges. Lately, there quality of life. SIT offers a useful option for these patients as
has been a move to assess efficacy in terms of improvements in well as a logical approach to dealing with the underlying problem.
quality of life or health gain per unit cost. These analyses are
becoming increasingly sophisticated but require careful validation SIT for Asthma
to ensure that the quality-of-life instrument is sensitive to the Immunotherapy has been widely used to treat allergic asthma,
illness being studied and that the economic model is realistic. but evidence of severe adverse reactions, including a small number
Finally, many trials of SIT for asthma and rhinitis have studied of fatalities, has led to SIT being abandoned for asthma treatment
laboratory surrogate markers, such as changes in IgG subclasses, in the United Kingdom since 1986, although asthma remains a
T-cell function, or skin test responses. Although such paraclinical common indication for SIT in North America and continental
measures do change during SIT and can shed light on the Europe. 12,14 There is no doubt that SIT is effective on asthma
mechanisms of successful SIT, they cannot be used to provide symptoms and protects against specific and nonspecific triggers.
direct evidence of clinical efficacy. Studies that show antibody However, the role of allergic sensitization in ongoing asthma is
or T-cell changes without direct clinical evidence of efficacy less clear than for rhinitis, and the risks of therapy are undoubtedly
neither support nor undermine the established evidence that greater in asthma. Current drug therapies for asthma aim to
SIT works, albeit in mysterious ways, to improve the symptoms suppress the airways inflammation and smooth muscle contrac-
of appropriately selected patients. Recent research on paraclinical tion, which are characteristic features of asthma. None of these
measures has identified four areas that may prove useful in future: treatments is curative, and asthma recurs rapidly upon cessation
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dendritic cell (DC) markers in sublingual immunotherapy (SLIT) ; of treatment. Moreover, current drug therapies are directed against
innate lymphoid cells (ILCs) favoring Th2 development (ILC-2), downstream mechanisms rather than against the agents that
which have been show to decrease in frequency after successful might cause asthma. Allergen avoidance has been proposed as
SIT; decreased expression of diamine oxidase—the enzyme a potentially useful maneuver in those with allergic asthma;
responsible for making histamine; and IgG antibodies that block however, although asthma control can be improved by extreme
IgE-mediated functional antigen presentation. 9 forms of allergen avoidance (e.g., admission to hospital, sending
children to holiday homes at altitude), there is little evidence
SIT for Allergic Rhinitis that similar benefits can be achieved by using the type of allergen
Allergic rhinitis is the main indication for SIT worldwide. As avoidance that can be achieved in suburban homes. Thus there
with all uses of SIT, it is important to select patients appropriately. is scope for improving asthma care and for identifying allergen-
The allergic basis of the rhinitis should be carefully assessed specific therapies. SIT offers the possibility of diverting the
during history taking and skin or blood tests for IgE, and other immune response away from the allergic pattern and toward a
relevant causes should be excluded. Tests of nasal sensitivity are more protective or less damaging response.