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Pollen Sensitization Among Egyptian Patients With Respiratory Allergic Diseases

Introduction: Pollen is responsible for seasonal allergies, such as allergic rhinoconjunctivitis (AR), and has become a growing public health concern. Climate change affects the range of allergenic species as well as the timing and length of the pollen season. In Egypt, data on pollinosis are scarce. Objectives: To detect the most prevalent pollen causing allergies among Egyptian patients with respiratory allergies. Methods: A total of 200 adult patients with respiratory allergic diseases (AR) and/or bronchial asthma (BA) were included. Medical history taking and physical examinations were conducted on each patient, and complete blood count (CBC) and total immunoglobulin E (IgE) determination, spirometry, specic IgE, and skin prick tests (SPTs) and for common aeroallergens and food were performed. Results: Of the 200 patients, 106 were females; the mean ± standard deviation was 34.42 ± 13.0 (range, 16 to 66), and 65% were living in urban areas. Grass pollen, mainly from Timothy grass and maize, were the most prevalent (28.5%). Timothy grass was the most common type of pollen in patients with AR (28.3 %). Elder pollen showed signicance among asthmatic patients (P = 0.004). Bermuda grass was statistically more prevalent in rural than in urban areas (P value = 0.008). Maize was linked to uncontrolled BA, whereas Timothy grass was the most prevalent among patients with moderate/severe AR. Forty-three patients had oral allergy syndrome; oranges and tomatoes were the most cross-reactive food (12% and 11.5%, respectively). Exacerbation of allergic symptoms was noted during January, December, March, and June. Conclusion: Pollen plays a substantial role in affecting patients with respiratory allergies in Egypt. Grass pollen is the most prevalent type of pollen, especially in urban areas.


Introduction
Allergic airway diseases, such as bronchial asthma (BA) and allergic rhinoconjunctivitis (AR), are major health and economic burdens because of their impact on quality of life, including social life, school attendance, and work performance [1]. Both genetic and environmental factors contribute to the development of allergic airway diseases, and one of the major environmental determinants causing respiratory allergy is pollen [2]. Pollinosis is characterized by a periodic repetition of symptoms during a speci c pollen season that varies between countries. Patients sensitized to both seasonal (e.g., pollen) and perennial allergens (such as house dust mites (HDM), cockroaches, and molds) have year-round symptoms of respiratory allergy and experience exacerbation during the pollen season [3]. Although the pollen season is related to the owering season, air pollution and climate change are the main in uencers of pollen allergenicity. Pollution, mainly in urban areas, leads to an increase in the pollen allergenic protein concentrations, with modi cations of unexpressed proteins into more allergenic components that induce allergies in sensitized individuals [4]. On the other hand, climate change affects the timing and length of the pollen season [5] as well as their geographical extent and distribution [6].
Grasses, weeds, and trees are the main sources of pollen allergens. Grass pollen, with its abundant production and wide distribution, is responsible for 40% of pollen sensitization [7]. Many studies in the United States showed that tree pollen was responsible for 25,000-50,000 hospital visits due to asthma during spring, whereas grass pollen was responsible mainly for summer visits [8]. On the other hand, weeds are more prevalent during fall [9]. Parietaria, ragweed, mugwort, sun ower, and Russian thistle are the main sources of weed pollen worldwide [10]. Cross-reactions between plant-derived allergens and aeroallergens in previously sensitized patients lead to oral allergy syndrome (OAS). OAS is an immediate hypersensitivity reaction that occurs when raw fruits or vegetables come into contact with the oral mucosa, resulting in itching of the lips, tongue, and throat [11]. OAS may be associated with more severe symptoms, such as angioedema or anaphylaxis, in 2-10% of cases. The main allergenic components involved in OAS are pro lins, pathogenesis-related protein 10, and lipid transfer proteins [12]. As only few studies have reported the prevalence of pollen allergy in Egypt, our study aimed to determine the most prevalent types of allergenic pollen among Egyptian patients with respiratory allergies.

Patient selection criteria
This cross-sectional study involved 200 adult patients (≥16 years old) who were newly diagnosed with respiratory allergic diseases, such as BA and/or AR, according to the GINA [13] and ARIA guidelines [14], respectively, and were recruited from the allergy clinic at Ain Shams University Hospitals from November 2017 to November 2019.

Exclusion criteria
Patients who were receiving allergen-speci c immunotherapy or those who recently received antihistamines or any drug that might interfere with the skin prick test (SPT) results were excluded from the study. Patients with dermographism and pregnant females were also excluded.

Methods
All patients were subjected to detailed medical history taking, including the frequency and timing of symptoms, history of pollen exposure, associated allergic conjunctivitis or OAS, assessments of asthma symptom control and AR severity using the GINA and ARIA guidelines, respectively, and spirometry for assessments of lung function and asthma control. From the peripheral blood samples, the CBC was obtained to determine the absolute eosinophilic count as well as the total IgE. SPTs and speci c IgE for common environmental aeroallergens and food allergens were also performed.

SPT
Brie y, drops of standard allergen extract provided by Bencard (Allergy Therapeutic Ltd., England) were introduced on the volar aspect of the patient's forearms while carefully pricking the skin using a blood lancet, and the results were interpreted after 20 minutes. Wheals ≥3 mm were considered positive [15].

Serum total IgE
An enzyme-linked immunosorbent assay was used for the quantitative determination of the total IgE level in human serum.

Spirometry
After the determination of patients' sex, age, height, and weight, patients were asked to fully inhale before beginning forced exhalation [17]. The ow-volume curves and the volume-time curves were then displayed [18]. Numerical values were given only for the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Grades of severity of obstructive airway diseases were interpreted according to the American Thoracic Society guidelines [19].

Statistical analyses
The data collected were revised, coded, tabulated, and introduced to a PC using the Statistical Package for Social Sciences (SPSS v20). Data were presented and analyzed according to the type of data obtained for each parameter. Parametric numerical data are presented as the mean ± standard deviation and range, whereas nonparametric numerical data are presented as the median and interquartile range (IQR). The chi-squared test was used to examine the relationship between two qualitative variables. P ≤ 0.05 was considered statistically signi cant.

Results
A cross-sectional study was conducted on 200 adult patients (≥16 years old) with newly diagnosed AR and/or BA who were randomly selected from an allergy and immunology clinic at Ain Shams University Hospital. All patients underwent detailed medical history taking and physical examinations; spirometry, CBC, and total IgE levels were obtained; and SPTs for common aeroallergens and food were performed.
The demographic data show that 106 (53%) were females. The mean age of the patients was 34.42 ± 13.0 years (range, 16-66 years). The majority of patients were living in urban areas (65%), and 60.5% had positive family history of atopy. AR was the most frequent respiratory allergy (117 patients), whereas 56 patients had both AR and BA.
The majority of patients were sensitized to grass pollen, which included Timothy grass, maize, and Russian thistle, whereas tree pollen caused the least sensitization among the pollen ( Figure 1).
The most prevalent pollen causing respiratory allergy in rural and urban areas was Timothy grass (34.3%) and maize pollen (29.2%), respectively. Regarding Bermuda grass, its prevalence in rural areas was signi cantly different from that in urban areas (P < 0.008) ( Table 2).
It was found that 145 (66.8%) patients with AR had pollen allergy, whereas 72 (33.2%) patients with BA were sensitized for pollen allergens. Elder pollens were the most statistically signi cant pollen among asthmatics (P < 0.004), whereas Timothy grass was the most prevalent pollen among patients with AR (28.3%). Patients who had mild intermittent AR (9) showed the greatest number of positive results to alder and maize (33.3%), whereas patients with mild persistent AR (4) showed the greatest number of positive results to Bermuda grass, Russian thistle, cultivated rye, and wheat pollen. In addition, patients with moderate/severe intermittent AR (89) showed the greatest number of positive SPT results to maize pollen (29.2%). Moreover, patients who had moderate/severe persistent AR (71) showed the greatest number of positive SPT results to Timothy grass pollen (32.4%) ( Table 3).
Patients with controlled asthma (15) showed the greatest number of positive results to alder pollen (26.7%). Patients with partially controlled asthma (60) showed the greatest number of positive results to maize pollen (30%). Patients with uncontrolled asthma (8) showed the greatest number of positive results to maize pollen (37.5%) ( Table 4).

Discussion
Pollen is divided into three main groups: grasses, weeds, and trees. Our study aimed to determine the most prevalent allergenic pollen among Egyptian patients with respiratory allergies (AR and/or BA). The study was conducted on 200 adult patients with newly diagnosed respiratory allergies.
Most of our patients with respiratory allergies were living in urban areas (65%), which agreed with a previous study that demonstrated that patients living in urban areas had a higher prevalence of polleninduced AR than patients living in rural areas (23.1% versus 14.0%, P < 0.001) [20].
This observation was previously explained by David Strachan, who noticed a reduced prevalence of asthma among children living on farms as increased exposure to pathogens during childhood resulted in tolerance to different allergens. He concluded that living in urbanized areas leads to reduced pathogen exposure, with a subsequent high risk of allergy [21].
In a study on 25,393 women, residents of rural areas had a lower odds ratio of developing allergies than residents of urban areas, relying on the fact that the former lived in areas with low levels of pollution, thus avoiding tra c-related air pollution, which is the main environmental cause of the high prevalence of allergies in urban areas [22]. Another fact supporting our results was that carbon dioxide (released in urban areas) acts as an important nutrient to plants, which allows the growth of a greater number of plants producing different allergenic pollen in urban areas, resulting in an increased allergy prevalence [23]. 21.5% of our patients complained of OAS symptoms. Two large Korean studies conducted on patients with respiratory allergy had results similar to ours, with the prevalence of OAS ranging from 20.0-41.7% [11,24].
Previous studies reported that 45-85% of patients with respiratory allergies were SPT-positive to HDM [25]. Frankland and El-Hefny were the rst to point out the high prevalence of people allergenic to HDM in Egypt, especially D. farinae, attributing Egypt's dry climate as a major reason behind the high prevalence. Since then, many studies have con rmed the widespread presence of HDM and other mites in domestic settings across Egypt and in the Middle East [26].
The prevalence of pollen allergy differs globally by region, depending on the climatic conditions. For example, Middle Eastern countries are known to have a dry, desert-like climate. Moreover, countries such as Egypt also have coastal regions with a Mediterranean climate [27]. Besides the effects of climate on the high diversity of pollen worldwide, introducing invasive allergenic pollen increases pollen prevalence, with new pollen sensitization [28].
In this study, grass pollen was the most frequent pollen allergen that patients were sensitized to, with 28.5% of patients reacting to Timothy grass and maize grass pollen. This was followed by Russian thistle (24%) and cultivated rye (23%), which are in contrast to tree pollen that has less frequent sensitization (elder, 7%; birch, 6%). Our results agree with the fact that grass pollen is one of the most frequent reasons for plant-related allergenic reactions worldwide. It is thought that at least 40% of patients with respiratory allergies worldwide are sensitized to grass pollen allergens [29], which comprise 9,000 different grass species (Poaceae) [30]. Timo et al. demonstrated that grass was the most frequent cause of pollen allergy in Europe and the USA. This is because grasses grow on every continent and in almost all types of environments. Grasslands were estimated to constitute 20-30% of the vegetation covering Earth, which explains the large percentage of grass pollen allergy globally [31]. Comparative studies from Middle Eastern countries, which include Egypt, Jordan, Kuwait, and the Kingdom of Saudi Arabia (KSA), showed that grass pollen was the most frequent allergen responsible for respiratory allergies among patients, with Bermuda grass being the most frequent in Kuwait and KSA [32][33][34][35].
On the other hand, a Chinese study that included 6,043 patients with AR revealed that most of these patients were sensitized to weed pollen [20]. Another study by Sung et al. in Korea found that the sensitization rate to trees (25.2%) was the highest among pollen types, with birch pollen being the highest among tree pollen (10.3%), followed by weeds (19.9%) (mugwort and ragweed) [36].
We found that 66.8% of patients with AR had pollen allergy, whereas 33.2% of patients with BA were positive to pollen allergens. The most prevalent pollen in patients with BA was maize pollen (26.5%), whereas Timothy grass pollen was the most frequent (28.3%) in patients with AR. In our study, tree pollen (elder) was signi cantly more prevalent in patients with asthma than in patients with AR. This could be explained by the fact that grass pollen, because of its large size, has a low probability of entering the lower airways and triggering asthma [37]. In contrast, tree pollen allergens have been recorded in sizes that are small enough to enter the lower airways, which may cause asthmatic responses in susceptible people [38].
To the best of our knowledge, we are the rst to report the relationship between the severity of AR and BA and the types of pollen allergens. Regarding AR, patients with moderate/severe intermittent AR showed the highest SPT positivity to maize pollen (29.2%). Meanwhile, patients with moderate/severe persistent AR showed the highest SPT positivity to Timothy grass pollen (32.4%). Patients with partially controlled asthma showed the highest positivity to maize pollen (30%), which was also true for patients with uncontrolled asthma (37.5%).
We compared the residency of the patients with the types of pollen and noticed that the most prevalent pollen types in rural and urban areas were Timothy grass (34.3%) and maize (29.2%), respectively, which means that grass pollen as a whole is prevalent throughout urban and rural areas. The high prevalence of grass pollen allergy in urban areas can be explained by the elevated levels of CO that have been shown to increase grass pollen production by 50% per ower [39]. Consistent with our results, a study conducted in Finland demonstrated that grass pollen exposure increased with the decreasing level of urbanization. This might be illustrated from the allergology point of view that the most urban environments, with small frequently managed patches of vegetation, have little potential to produce considerable amounts of pollen grains and to expose people to pollen. Thus, staying in urban environments would reduce the overall exposure to grass pollen, although occasionally higher levels of exposure may be encountered [31].
In addition, our study revealed that the prevalence of Bermuda grass pollen was higher in rural areas than in urban areas, and the difference was statistically signi cant (P value = 0.008). However, Jorge et al. in Colombia disagreed with this, and they aimed to explore whether the growth conditions of the Bermuda grass pollen modify the allergic response of patients with AR in rural versus urban areas. They concluded that Bermuda grass pollen was more prevalent in urban areas, and its growth conditions modify its allergenicity [40].
There were monthly variations in the frequency of exacerbations during the study period. Peaks of allergic respiratory diseases recorded in January, December, March, and June were 26.5%, 21.5%, 18%, and 16%, respectively. This could be explained by the higher rate of viral infections and allergen exposure during winter (December and January), pollination of the majority of pollen during spring (March), and when the grass pollen is at its peak (late spring) (June), with a lower level of exacerbation in summer when the climate becomes drier. Our results could be easily illustrated by research performed on the onset and duration of several allergenic pollen types in the USA, indicating that the start dates for the appearance of signi cant allergens is prevalent earlier in the year (January). Another fact is that grass pollen is present in the air during late spring and early summer (March and June) [22].
In this study, the most prevalent cross-reactive food with pollen, as evidenced by the SPTs, were oranges (12%), followed by tomatoes (11.5%) and soya (11%). We demonstrated that tomatoes were highly crossreactive with Timothy grass (43.5%) and maize pollen (39.1%). Oranges were highly cross-reactive with cultivated rye and Russian thistle (33.3%). Soya was highly cross-reactive with cultivated rye (36.4%), Timothy grass (27.3%), and Russian thistle (27.3%). In line with our study, a paper published by the EAACI demonstrated that 60% of food allergies in adults are linked to an inhalant allergy [41]. Another study in Bosnia revealed that 50% of the study population was allergic to Timothy grass, which was highly correlated with tomatoes, melons, and peanuts [42]. Vieths et al. performed a study on the cross-reactivity between allergens and pollen, and they revealed that there was a signi cant cross-reaction between grass pollen and tomatoes and oranges. This may be attributed to the fact that pro lins and cross-reactive carbohydrate determinants, which are present in grass pollen, are also present in different fruits and vegetables, such as oranges and tomatoes [43].
The limitations of this work are that it was conducted in a single center with a relatively small sample size. Moreover, the lack of molecular techniques to study the different allergens used in this study may add to our limitations.
In conclusion, pollen plays a substantial role in patients with respiratory allergies in Egypt. In addition, grass pollen is the most prevalent type of pollen, especially in urban areas.

Declaration
Ethics approval and consent to participate The study was conducted according to the Medical Association Declaration of Helsinki. Informed written consent was obtained from all the participants. The study had been reviewed and approved by the Research Ethics Committee at the Faculty of Medicine, Ain Shams University (reference MD 292/2017). This manuscript doesn't report on the use of any animal or human data or tissue.

Consent for publication
Not applicable Availability of data and materials All data sets generated during and/or analysed during the current study are available in this published article.
Authors' contributions MR designed the study. NN, MM were responsible for data collection. MM prepared the manuscript. OA , NA and EA shared in data analysis and critical revision of the manuscript . All authors read and approved the nal manuscript.      Figure 1 Prevalence of different pollen among patients with respiratory allergies (%).

Figure 2
Peaks of exacerbation of respiratory allergies (there were multiple peaks when patients with allergic respiratory diseases suffered the most during certain months of the year).