Sublingual immunotherapy for asthma: need for high quality meta‐analyses to prove the concept

We reviewed carefully the report on SLIT in asthmatic patients by Calamita et al. (1) presented in an earlier issue of this journal. We were members of a Joint Task Force that recently published an extensive review on SLIT (2) that included much of the same articles as contained in Calamita’s publication. The following points drew our attention. We found that the paper has some numerical and logistical discrepancies. Many studies included are papers on SLIT in patients with rhinitis/rhinoconjuntivitis with or without mild intermittent or mild persistent asthma. Sub-analysis of the results for the asthma only a patients were generally not given, so the direct impact on asthma is hard to deduce from these studies. In a meta-analysis of safety and efficacy of SLIT in the treatment of asthma, only the asthmatic patients should be considered. This does not appear to be the case in this meta-analysis because there were at most 609 patients with asthma in the studies reviewed (see Table 1). This meta-analysis provided safety data on 830 patients, although the number of asthmatic patients enrolled in the studies reporting safety was 504 (see Calamita et al’s paper, Fig. 3). This discrepancy in the number of patients included in the safety and efficacy analysis could significantly alter the results of the analysis. Moreover, when Calamita et al. analyzed the overall impact of SLIT on asthma improvement, the table plots the total number of patients with worsening of asthma and not the number of asthma patients who improved. Probably the most important paper in this efficacy figure 2, with an impact size of 55% is the Marogna 2004 paper with 319 patients in the active group. However, only 191 of the 319 had asthma. Also added to figure 2 of asthma worse is the paper from November 2004, which only included patients with rhinitis/ rhinoconjuntivitis in the study, but then reported the number of subjects who developed asthma during the trial. In this case, not developing asthma is thus added under the heading of asthma improvement . Three publications not included in Calamita et al.’s analysis provided clear safety and efficacy information about SLIT in asthma patients. A randomized placebo controlled study of asthmatic patients receiving SLIT provided outcome data in terms of FEV1 and PC20, with columns and bars indicating standard deviations (3). Another study was reportedly excluded, because no asthmatic patients were included (4). However, reading the paper carefully there were 10 asthmatic patients, more than in two studies Calamita et al. did include in the meta analysis: Passalacqua (1998, 1999) with 3 and 6 asthmatic patients. Finally, a double blind placebo controlled trial of SLIT in 86 children with asthma from Ippoliti et al. (5) was excluded because of lack of data, but the study reported the exact reduction in pulmonary symptoms and FEV1 with P < 0.001. To finish, some numerical deviations are the Niu paper with 97 and not 110 patients and the studies from Werninghaus 2004 and Purello d’Ambrosio 1999 with just 20 and 7, instead of 39 and 14 asthmatics (Fig. 4, Calamita et al’s paper).