Evaluation of quality of life of patients with pollen allergy before and after sublingual immunotherapy course

In Ukraine, there are over 1.5 thousand types of weeds, which may provoke the development of allergic reactions. Based on our observation, most commonly sensitization to Artemisia and less often to Ambrosia is recorded in patients of Lviv region. The presence of clinical symptoms significantly deteriorates life quality of patients with pollen allergy and requires conduction of proper allergy immunotherapy.


Introduction
Allergy to weed pollen is quite common worldwide including Ukraine. It is known that over 1.5 thousand types of weed plants grow on the territory of our country, which may provoke the development of allergic reactions. The most common clinically significant weed allergens worldwide are present in the pollen of Artemisia, Ambrosia, orach, plantain, and saltwort [1].
The main clinical manifestations of allergy to weed pollen are allergic rhinitis/rhinosinusitis (AR), conjunctivitis and bronchial asthma (BA). Thus, symptoms vary in patients, and in most cases, there are rhinorrhea, sneezing, itching, conjunctivitis, cough, breathlessness, etc [2]. This condition is considerably deteriorated due to a person's quality of life (QOL) and often results in temporary disability.
The basic method of treatment of sensitized patients with clinical manifestations of allergy to weed pollen is allergy immunotherapy (AIT). Currently, there are many evidence investigations concerning AIT efficacy in patients with pollen allergy. However, the majority of them focus only on the analysis of AIT influence on reduction of clinical manifestations or comparison of efficacy of different AIT methods (sublingual, subcutaneous, etc.) [3].
Nowadays there is a need in paying more attention to investigations concerning estimation of QOL of patients with allergic pathology, especially after treatment. Undoubtedly, implementation of the notion "QOL" into somatic medicine practice can be considered a significant progress compared with the traditional tendency to focusing solely on the disease and its symptoms. Besides, medical aspects of QOL define not only patients' health condition, but also the condition of social, material, intellectual and mental well-being, etc. [4].

The aim
The aim of our research was to analyze QOL of patients with allergy to weed pollen before and after conduction of sublingual immunotherapy (SLIT) based on specialized questionnaire MiniRQLQ.

Materials and methods
This cohort prospective investigation was performed at the department of clinical immunology and allergology of Danylo Halytsky Lviv National Medical University and in Lviv regional medical center of clinical immunology and allergology, Ukraine, with the participation of Medical Intern of Shupyk National Medical Academy of Post-Graduate Education. The research had been lasting for three years starting from March 2014.
In the given period, 485 individuals aged from 3 to 67 years were examined (average age 24.0 ± 4.5), 291 males (60.0 %), 194 females (40.0 %). The criteria for inclusion were age from 18 years, clinical diagnosis of AR made according to ARIA criteria (2014), and sensitization to at least one weed extract (Ambrosia and/or Artemisia (according to the data of skin prick tests (SPT). The criteria for exclusion were combination of AR and BA, age under 18, adults who had received AIT previously, the presence of mental, lingual and cognitive disorders. Thus, 122 individuals were selected for further investigation.
At the time of selection, patients' allergy symptoms were evaluated and analysis of case history was done. Total laboratory, instrumental and specific immunological investigations were performed, in particular, SPT to standard inhaled allergens (Diater-Laboratories, Spain): Der. pteronyssinus, Der. farina, a mixture of spring trees, a mixture of grass, Artemisia, Ambrosia, Alternaria alternata, cats and dogs [5]. Determination of total serum and specific immunoglobulins IgE (sIgE) class was performed with enzyme immunoassay using test-systems Euroimmun. For detection of the levels of specific IgE class antibodies, ImmunoCAP (Thermo Scientific, Uppsala, Sweden). Three marker allergens of genuine sensitization to pollen of Artemisia (nArt v 1, rArt v 3) and Ambrosia (rAmb a 1) were determined. Levels of sIgE >0.35 KU/l were considered positive. Totally, 71 individuals with AR received a two-year course of immunotherapy using sublingual allergens of Artemisia and Ambrosia Diater, Spain. Patients of the second group received symptomatic treatment in the form of non-sedative antihistamines (tablets, eye drops, nasal sprays etc.). Monitoring of QOL was conducted before therapy (SLIT or symptomatic) and after the first and the second years of treatment, during visits for consultations. More data are given in Table 1.
The study was conducted in accordance with the seventh revision of the principles of the Declaration of Helsinki on Human Rights (2013). Information consent was received from the patients.

Analysis QOL
Analysis of life quality was conducted based on validated questionnaire MiniMRQLQ. The MiniRQLQ has 14 items in five domains (activity limitation [n = 3], practical problems [n = 2], nose symptoms [n = 3], eye symptoms [n = 3] and other symptoms [n = 3]). The questionnaire is in a self-administered format and is completed by patients without an interviewer's assistance. Patients are asked to consider how they have been and to respond to each question on a seven-point scale (0 = not troubled, 1 = hardly troubled at all, 2 = somewhat troubled, 3 = moderately troubled, 4 = quite a bit troubled, 5 = very troubled, 6 = extremely troubled).
The statistical processing of the obtained results was made using freeware Libre Office calc 6.1 for Ubuntu 16.04 LTS. We applied the Wilcoxon (sum of the signed ranks) criterion to define the probability of changes in patients' life quality after the 1 st and the 2 nd years of treatment inside the groups. We applied the Mann-Whitney U-test to define the probability of changes in patients' life quality after the 2 nd year of treatment between the 1 st and the 2 nd groups.

Results
Among 472 patients with pollen allergy, positive SPT to weeds were detected in 122 (25.8 %) individuals. Among them, monosensitization to Artemisia was in 7 (5.7 %) persons, monosensitization to Ambrosia -in 3 (2.5 %) individuals. As predicted, polysensitization was observed in 112 (91.8 %) patients. Among polysensitized individuals, positive SPT to Artemisia were detected in 69 (61.6 %), to Ambrosia -in 14 (12.5 %) patients, combined sensitization to two types of weeds was found in 29 (25.9 %) patients. Thus, sensitization to Artemisia was observed in 76 (62.3%) individuals, to Ambrosia -in 17 (13.9 %), co-sensitization -in 29 (23.8 %) persons. Therefore, to detect genuine sensitization to Artemisia and Ambrosia for selection of a correct treatment tactics, we offered patients with mono-and polysensitization to perform allergen-component analysis. Among 76 patients with positive SPT to Artemisia, the presence of genuine  Using validated mini-questionnaire MiniRQLQ for patients in both groups, QOL estimation was performed before treatment and after the first and the second years of SLIT (the 1 st group) and symptomatic treatment (the 2 nd group). Data of analysis are given in Table 2.
The reliable decrease of all indices was established in patients of both groups following SLIT after the first and the second years of treatment (P < 0.01), except eye symptoms for the 2 nd group after the first year of treatment (P < 0.05). The reliable decrease of experienced allergy symptoms (P < 0.05) was also estimated in patients after the second year of SLIT in compare with the control group with symptomatic treatment.

Discussion
Currently, to specify QOL in patients with rhino-conjunctivitis, two basic questionnaires are used: RQLQ (rhino-conjunctivitis quality of life questionnaire) and Mini RQLQ (mini-rhino-conjunctivitis quality of life questionnaire). Usually, MiniRQLQ is used in clinical investigations, since it is more convenient as it contains fewer questions compared to RQLO, however, it is not less valid than the latter. In particular, in Indian investigation conducted in Mumbai, QOL of patients with atopic dermatitis (AD) was studied, using MiniRQLQ. The results showed that patients with AD most often experienced symptoms, associated with rhinitis; Emotion-associated and Role limitation items were moderately revealed, while eye related, Physical functioning, Social functioning, Sleep-related & Other Symptoms items were in the low range [6].
In our examination of patients with allergy to weed pollen based on MiniRQLQ questionnaire, we observed positive changes of QOL indices, indicating the efficacy of SLIT compared with symptomatic therapy. A reliable reduction of indices was observed in patients of the first group both after the first and the second year of SLIT (P < 0.01). The majority of patients in this group noted a significant alleviation of physical and mental condition, since reduction of clinical symptoms in pollination season allowed them to drive a car for a long time, join sport groups, carry out everyday duties actively etc. There was tendency to improvement of seasonal clinical symptoms only in four persons of the first group among polysensitized individuals. This fact is due to exacerbation of symptoms caused by the influence of other allergens. Besides, several patients in SLIT period had frequent respiratory viral diseases, and thus, decreased immune activity and temporary cessations of SLIT. Further, 68 patients agreed to continue SLIT, and three patients refused to proceed with the treatment due to personal causes.
In patients of the second group we also observed the reliable tendency to improvement of QOL indices after the symptomatic therapy. As expected, patients of the second group noted that clinical manifestations of allergy exacerbated from the end of July -the beginning of August (depending on weather conditions) and could only be controlled due to proper symptomatic therapy. In this group, 11 patients observed a slight reduction of clinical symptoms associating it with temporary change of living place (they moved to seashore); and five individuals noticed deterioration of their condition (clinical symptoms exacerbated and breathlessness appeared). It should be mentioned that eight patients of the second group decided to undergo SLIT in the future.