Study design and patients
This was a cross-sectional study of consecutive patients admitted to the otorhinolaryngology department of three hospitals in the Balearic Islands (Spain) due to symptoms of respiratory allergy between October 2012 and November 2013. The inclusion was restricted to patients of both sexes, aged between 7 and 60 years, who had been living in the same area for at least 5 years, had experienced symptoms of a respiratory allergic disease (i.e., rhinitis, asthma or both) for at least 2 years and had a positive reaction to an allergen as determined by SPT. Patients who received immunotherapy within 5 years prior to admission or who had no diagnostic tests performed were excluded from the dataset.
Variables and endpoints
Demographic and clinical characteristics included age, sex, time from symptoms onset to diagnosis, type of respiratory allergic disease (rhinitis, asthma or rhinitis with concomitant asthma), frequency of symptoms (perennial or seasonal), and severity of the allergic disease, which was rated as mild or moderate-to-severe, based on the Spanish guidelines on the management of asthma (GEMA) [14, 15] and allergic rhinitis with impact on asthma (ARIA) [16]. Other clinical data included concomitant food allergies, and personal and/or family history of allergy. Allergen sensitization was determined using both SPT and CRD. Patients sensitized to more than one extract (SPT) or to specific IgE of more than one species (CRD) were considered polysensitized.
Skin prick test, performed according to the European Academy of Allergy and Clinical Immunology guidelines [17], was considered positive if wheals and flares were observed within 15 min, and wheal mean diameter was ≥ 3 mm. The following extracts were tested by SPT: House dust mites Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Lepidoglyphus destructor; pollens Olea europaea, Artemisia vulgaris, Plantago lanceolata, Platanus hispanica, Parietaria judaica, Salsola kali, Cupressus sempervirens, and grass mixture; molds Alternaria alternata. Panallergen profilins, polcalcins, non-specific lipid transfer proteins (nsLTPs), and tropomyosins were also analyzed. Histamine and saline solution were used as positive and negative controls, respectively. Allergen extracts were provided by ALK-Abelló, S.A. (Madrid, Spain).
Allergen-specific IgE was quantified using chemiluminescent acridinium on the ADVIA Centaur platform (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY, USA) as described by Petersen et al. [18]. CRD was considered positive when binding values exceeded 0.35 kU/L. The CRD analysis screened the presence of specific IgE against the following molecules: Der p 1 and 2, Der f 1 and 2, and Lep d 2; Ole e 1 and 9, Art v 1, Pla l 1, Phl p 1 and 5, Pla a 1 and 2, Par j 2, Sal k 1, Cup s 1;Alt a 1; Pho d 2, Che a 3, Pru p 3, Der p 10, and Pen a 1.
Statistics
Quantitative variables are described as mean and standard deviation (SD) or as median and interquartile range (IQR), whereas categorical variables are presented as frequencies and percentages. Differences between groups (according to type and severity of the disease, frequency of symptoms, diagnostic method) were analyzed using the Fisher exact test or the non-parametric Wilcoxon test. Concordance between SPT and CRD methods was assessed by Cohen’s kappa coefficient (κ). Associations between demographic and clinical factors and the most prevalent sensitizations were determined by logistic regression analyses, with age, time from onset of symptoms to diagnosis, type and severity of the disease and concomitant food allergies as the independent variables. The threshold for statistical significance was established at a two-sided alpha value of 0.05. All statistical analyses were performed using the SAS 9.3 software.