To the Editor,
About 5% to 10% of all patients with asthma suffer from severe asthma,
(1) which frequently is caused by IgE-mediated hypersensitivity against
perennial and/or seasonal allergens. Anti-IgE treatment is efficacious
and approved for the treatment of severe allergic asthma. To be eligible
for omalizumab treatment, patients must be sensitized to a perennial
aeroallergen, demonstrated either by skin prick test or by serum
specific IgE.
It has been suggested that Omalizumab was efficient in non atopic
asthmatic patients (2). However, negative skin prick tests or specific
IgE measurements to common aeroallergens may occur because the patient
was sensitized to an untested allergen (3). In patients considered as
non atopic, extended panel of aeroallergen found that Staphyloccocal
enterotoxin (SE) sensitization was one of the most prevalent (3).
Therefore, we hypothesized that the efficacy of Omalizumab in patients
considered as non atopic could be caused by a sensitization to SE.
This single-center, retrospective real life study was performed in the
Chest Diseases Department of Strasbourg University Hospital, including
54 severe asthmatic patients according the 2018 GINA guidelines, treated
with omalizumab. All patients underwent an evaluation by the same
physician trained for severe asthma at initiation and 4 months after
omalizumab treatment. The assessment was based on a clinical evaluation.
Variables of interest are reported in Table 1. Patients were defined as
sensitized to common aeroallergen if they had at least one positive
prick test to the following allergens: mite, cat, dog,aspergillus, alternaria , grass, birch, ash, ragweed and mugword
pollen (ALK Lab, Varennes-en-Argonne, France ). Sensitization to SE was
determined by specific IgE measurement (positivity threshold
> 0.1 kUA/L Thermofisher).
Out of 54 asthmatic severe patients treated with Omalizumab 32 were
considered responders.
Prevalence of sensitization to SE was to 61% in all patients, to 52.2%
in patients not sensitized to common aeroallergen, and to 67.7% in
patients sensitized to common aeroallergens (p = 0.273). Chronic
RhinoSinusitis with Nasal Polyps (CRSwNP) was observed more frequently
in patients not sensitized to common aeroallergens but sensitized to SE
(Table1). They were also more frequently treated by oral corticosteroid.
Total IgE count was higher in patients sensitized to SE (Figure 1).
No difference was observed in term of response of omalizumab regarding
the sensitization to SE. In multiple logistic regression no association
was found between efficacy of omalizumab and sensitization to SE after
adjustment with gender, body mass index, total IgE count, CRSwNP, oral
corticosteroid at baseline, and the sensitization with commun
aeroallergens (OR 1.47; 95% CI, 0.4-5.4; p= 0.558).
Sensitization to SE did not appear as a marker of efficacy of omalizumab
in severe asthmatics not sensitized to common aeroallergens.
Consequently, the efficacy of Omalizumab could not be explained by an
anti-IgE effect against SE. The absence of standardized evaluation of
omalizumab response, the limited population, and the retrospective
design could have been limitations. However, we found similar results as
larger studies. Indeed, we showed that frequency of sensitization to SE
was high in severe asthmatics sensitized or non to common aeroallergens.
In EGEA cohort, prevalence of SE sensitization was close to our result (
62.2 and 75.6% )for moderate to severe asthma (4) . Moreover, SE
sensitization appears more frequently with CRSwNP and high total IgE
count. this confirms previous publications (5) (6).
Even though larger prospective studies would be needed to evaluate the
association between SE sensitization and omalizumab efficacy in severe
asthma, no tendency was found in our study.
1. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ et al.
International ERS/ATS guidelines on definition, evaluation and treatment
of severe asthma. European Respiratory Journal2014;43 :343–373.
2. Garcia G, Magnan A, Chiron R, Contin-Bordes C, Berger P, Taillé C et
al. A proof-of-concept, randomized, controlled trial of omalizumab in
patients with severe, difficult-to-control, nonatopic asthma.Chest 2013;144 :411–419.
3. Schreiber J, Bröker BM, Ehmann R, Bachert C. Nonatopic severe asthma
might still be atopic: Sensitization toward Staphylococcus aureus
enterotoxins. Journal of Allergy and Clinical Immunology2019;143 :2279-2280.e2.
4. Sintobin I, Siroux V, Holtappels G, Pison C, Nadif R, Bousquet J et
al. Sensitisation to staphylococcal enterotoxins and asthma severity: a
longitudinal study in the EGEA cohort. Eur Respir J2019;54 :1900198.
5. Bachert C, Zhang N, Holtappels G, De Lobel L, van Cauwenberge P, Liu
S et al. Presence of IL-5 protein and IgE antibodies to staphylococcal
enterotoxins in nasal polyps is associated with comorbid asthma.Journal of Allergy and Clinical Immunology2010;126 :962-968.e6.
6. Kowalski ML, Cieślak M, Pérez-Novo CA, Makowska JS, Bachert C.
Clinical and immunological determinants of severe/refractory asthma
(SRA): association with Staphylococcal superantigen-specific IgE
antibodies: Staphylococcal superantigen specific lgE in asthmatic
patients. Allergy 2011;66 :32–38.