Asthma


Specific Immunotherapy for Allergic Asthma Giovanni Passalacqua


Professor of Respiratory Medicine and Allergy, Allergy and Respiratory Diseases, University of Genoa


Abstract


The use of specific immunotherapy in asthma is still debated, since there have been few studies specifically designed for asthmatic patients and the effects of specific immunotherapy on functional respiratory parameters have been assessed only rarely. On the other hand, there have been good-quality studies conducted with subcutaneous and sublingual immunotherapy in patients with allergic rhinitis, which have showed positive results on concomitant asthma as well. In this area, several meta-analyses are also available, confirming a positive clinical effect. The disease-modifying effect of specific immunotherapy – that is, the ability to prevent the onset of asthma in patients with allergic rhinitis – and the long-term effects should also be taken into account. Fatalities are an exceptional event and, in Europe, no deaths attributable to immunotherapy have been reported in the last two decades. Uncontrolled asthma is recognised as the most important risk factor for severe adverse events, while immunotherapy seems not to induce asthma exacerbations in controlled patients. Therefore, the efficacy of subcutaneous and sublingual immunotherapy in allergic asthma associated with allergic rhinitis is well supported by the literature. In such cases, immunotherapy reduces symptoms and medication intake. Currently uncontrolled asthma is a contraindication to start immunotherapy. Specific immunotherapy cannot be recommended as the first-line or only treatment when asthma is the sole manifestation of respiratory allergy.


Keywords Allergic asthma, allergic rhinitis, sublingual immunotherapy, subcutaneous immunotherapy, safety, efficacy, prevention, meta-analysis


Disclosure: The author has received in the past speaking and consultant fees from Anallergo, ALK-Abellò, Lofarma and Stallergenes, none of which are related to this article. Received: 16 August 2011 Accepted: 1 September 2011 Citation: European Respiratoy Disease, 2011;7(2):97–100 Correspondence: Giovanni Passalacqua, Professor of Respiratory Medicine and Allergy, Allergy and Respiratory Diseases, Department of Internal Medicine, Padiglione Maragliano, L.go R. Benzi 10, 16132 Genoa, Italy. E: passalacqua@unige.it


Although allergen immunotherapy, or specific immunotherapy (SIT), is specific for the allergen and not for the disease (rhinitis or asthma),1


for


historical reasons the effects of SIT are still considered separately for the two disorders. The use of SIT in asthma has been and continues to be debated,2–4


Another inherent problem is that the majority of clinical trials were performed in patients with allergic rhinitis (with or without asthma), with few trials specifically designed for asthma. In addition, none of the trials evaluating asthma symptoms was adequately designed (sample size, power analysis, outcomes) or reported.6,7


especially in terms of safety. It is well known that, in the past, fatalities attributable to SIT occurred mainly in asthmatic patients and that the first European official report on fatalities concerned patients with asthma.5


Finally,


there is no consensus on which measurement parameters for asthma should be chosen: asthma symptoms, rescue medications, asthma-free days, forced expiratory volume in one second (FEV1) or asthma exacerbations7,8


(see Table 1). However, there are numerous well-conducted trials of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in rhinitis that also evaluated asthma, such that a reasonably balanced evaluation can be attempted.


Efficacy


Numerous clinical trials of SCIT describing its effects in asthma were performed before the publication of the World Health Organization (WHO) official document on SCIT,1


which includes 32 placebo-controlled


trials. Many of the studies were not specifically designed for asthma but did evaluate asthma symptoms. These studies substantially agree on the


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clinical efficacy of SCIT in asthma induced by the most common allergens (such as grass or mites), and only 25 % of the studies listed in the WHO position paper failed to show a significant difference between placebo and active groups. After the WHO position paper, at least 20 new randomised controlled trials9


were published. Again, none of the


studies had a sample size calculation, the inclusion criteria and outcomes were largely variable, the methodological quality was overall low and the reporting did not fulfil the Consolidated standards of reporting trials (CONSORT) criteria. Some trials reported totally or partially negative clinical results,10–12


but the majority of the trials demonstrated an improvement of asthma symptoms and/or a reduction


in the intake of asthma drugs. Lung function parameters – either FEV1 or peak expiratory flow rate – were measured in only a few trials12–14


with controversial results, whereas a reduction in bronchial non-specific and specific responsiveness was repeatedly described.


The relatively high number of studies evaluating asthma symptoms means that meta-analysis is possible. The most recent meta-analysis15 includes 88 controlled trials (70 placebo-controlled) published between 1954 and 2009 (see Table 2). The methodological quality, assessed by the Jadad score, was low to moderate, with only six trials receiving the maximum score of five points. Concealment of allocation was considered adequate in 16 trials and insufficient in 15. Symptom scores were reported in 35 studies and medication scores in 21, while only 20 studies had a pulmonary function measurement. There was only a borderline reduction of symptoms with mite


97 and


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