Ethics
The Institutional Review Board of Peking Union Medical College Hospital approved the study. Verbal informed consent was obtained from each patient and the parents of all participating children. All the evaluated parameters were obtained from the routine examination of the allergy department. The researchers adhered to the voluntary principle of participants and paid attention to protecting the privacy of participants.
Population
A cross-sectional study of 393 patients with allergies was conducted (Fig. 1). The participants comprised of children and adults (6–76 years old) from North China and had nasal allergies with/without asthma. A thorough medical history taken by senior allergists detailed their history of asthma, cough, allergic rhinitis, their parental history of allergies, drug allergies, food allergies, and living environment. The temporal sequence of allergic rhinitis and asthma and the use of asthma medications were reviewed. All participants underwent intradermal skin tests (IDT) to inhaled allergens (house dust mites, Artemisia, Humulus, Juniper, Sycamore, Ash, Alternaria, Cladosporium, cat hair, dog hair), and sIgE tests to house dust mite.
Case selection
The selection excluded 10 patients without rhinitis and asthma, and 62 patients with asthma only. 321 patients with rhinitis but with/without asthma were retained. In the 321 patients with allergic rhinitis, 108 had only allergic rhinitis when they were interviewed in 2009, and 213 had both allergic rhinitis and asthma. The individuals involved in the analysis meet the following criteria: All suffer from allergic rhinitis; Recurrent nasal itching, sneezing, rhinorrhea, and hyperemia; Clearly living environment; Clearly with or without allergic asthma; All sIgE serum tests of house dust mites were conducted; All kinds of inhaled allergens are tested for the skin.
Definitions
Allergic rhinitis (AR) is a hypersensitivity reaction caused when inhaled particles contact the nasal mucosa and induce an immunoglobulin E (IgE)-mediated inflammatory response, which is often accompanied by ocular pruritus, redness and/or lacrimation.[7]
The diagnosis of allergic rhinitis was made on clinical grounds based upon the presence of characteristic symptoms (i.e., paroxysms of sneezing, rhinorrhea, nasal obstruction, nasal itching, postnasal drip, cough, irritability, and fatigue), a suggestive clinical history (including the presence of risk factors), and supportive findings on physical examination. Besides, a positive skin test for inhaled allergens confirmed that the patient's symptoms were related to the allergies.
Asthma was defined by allergist in the 2009 cross-sectional survey when the participants had a history of recurrent dyspnoea, wheezing or cough episodes, positive airway reversibility testing (FEV1 increasing > = 12% and 200 mL after inhalation of 400 mg of salbutamol or treatment with inhaled glucocorticoid or anti-leukotriene drugs for 4–8 weeks).[8]
Measurement of serum specific IgE
sIgE was measured using ImmunoCAP (Phadia1000, Thermofisher Scientific). sIgE with a value of 0.35 kU/L or more (0.35-100kU/L) were considered sIgE-positive. sIgE were divided into six degrees: Class 1: values ≥ 0.35–0.7 kU/L, Class 2: values ≥ 0.7–3.5 kU/L, Class 3: values ≥ 3.5–17.5 kU/L, Class 4: values ≥ 17.5–50 kU/L, Class 5 : values ≥ 50–100 kU/L, and Class 6: values ≥ 100 kU/L.
Intradermal skin test (IDT)
IDT was performed with commercial allergen extracts (Xinhualian ®, Beijing) according to a standard protocol. Experienced nurses performed IDT. The allergists read the IDT results. Intradermal tests were performed using a series of common aeroallergens, including house dust mites, Artemisia, Humulus, Juniper, Sycamore, Ash, Alternaria, Cladosporium, cat hair, dog hair. For positive and negative controls, we used histamine chlorhydrate at 0.1 mg/mL and 0.9% saline solution. Skin reactions were interpreted at 15 minutes after skin testing and found to be positive when the diameter of the wheal was > 5 mm with local erythema. The following grading system was used according to the criteria that our department established[9]:
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Wheal < 5 mm and no or small erythema = negative
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Wheal 5–10 mm and small erythema = 1+
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Wheal 10–15 mm and erythema > 10 mm = 2+
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Wheal > 15 mm and erythema > 10 mm or with pseudopod formation = 3+
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Local response as grade 3+, accompanying with systemic allergic reaction = 4+
Statistical analysis
Univariate analysis was performed to estimate Crude Odd Ratios (OR value), and a significance value of 0.05 was used to generate a 95% confidence interval (95% CI). Logistic regression analysis was used to analyze the effect of house dust mite sIgE levels on patients with asthma based on allergic rhinitis. Four models were established for regression analysis, and adjusted OR values were obtained. In model 1, only house dust mite sIgE was involved. In model 2, based on sIgE, age at visiting clinics and gender were added. In model 3, food allergy and living environment were added, whose p values with sIgE were smaller than 0.05 in the Pearson correlation test. Drug allergy, allergic rhinitis duration, family allergy history, and having pets in the family were added into model 4 based on model 3. The new parameters were factors often considered by clinical allergists.
Kaplan-Meier survival function model was used to estimate the survival rate of asthma based on allergic rhinitis. The time range for the group with both rhinitis and asthma is from the first allergic rhinitis attack to the first asthma attack. For the group with rhinitis only, the time range is from the first allergic rhinitis attack to the time when patients came to our hospital. The survival function analysis was used to obtain the zero to five years Rhinitis-Asthma Conversion Rate (RACR) of rhinitis patients at different house dust mite sIgE levels.
Logistic regression analysis was used to analyze the confonding and interaction of house dust mite sIgE and other allergens. The diagnosis of patients allergic to other allergens mainly comes from intradermal tests. The analysis was performed with SPSS version 25 for MAC (SPSS Inc., Chicago, IL, USA).