Pattern and Severity of Allergic Rhinitis Correlated with Patient Characteristics: A Rural Hospital-Based Cross-Sectional Study

Abstract

Allergic Rhinitis (AR) is rising in incidence in both developed and developing countries. Genetics and epigenetics have a potential role to play. The pattern and severity of AR have implications with regard to choice of treatment, which itself could be related to patient specific genetic and epigenetic factors. Hence, the present study was undertaken to correlate the patient characteristics with AR pattern and severity, in order to understand the pathophysiology of AR. The study also aimed to find out the allergen sensitivity pattern among patients attending a tertiary care centre of rural central India, where climatic variations make it a high prevalence zone. Prospective Observational study on 90 patients with clinically diagnosed Allergic Rhinitis confirmed by Skin Prick Tests. Patient characteristics like demographic data, data relevant to allergen exposure, occupation, family history of atopy and gender; and Disease characteristics like severity (mild, mod-severe), pattern (continuous/ intermittent), type of disease (seasonal/perennial) were noted, analysed and correlation studied. Majority of the patients with AR were in the age group of 15–40 years. Medical students (52%) suffered from moderate to severe type of Allergic Rhinitis, with Persistent disease in approximately 80%. Similarly, 70.59% of farmers had moderate to severe type of the disease, with persistent disease in 70%. In the present study, in clinically diagnosed allergic rhinitis patients, Mite was the commonest allergen found on Skin Prick Test overall and in Medical students, whereas Pollen sensitivity was more common among farmers. 56.66% of the patients had negative family history of atopy. Severity and type of AR depend on allergen exposure. In farmers and medical professionals, persistent and moderate to severe type of disease was more common, as they were persistently exposed to different type of allergens, mites in case of medical professionals and pollens in farmers. Hence, the Disease characteristics, as defined by ARIA guidelines, should not be taken in isolation and management should consider the Patient characteristics for deciding and devising protocols. In the present study, more than 50% patients were without family history of atopy. Hence, the role of various environmental factors, leading to epigenetic changes could be a major contributor in the increase in incidence of allergic rhinitis in recent times. Occurrence of perennial moderate to severe form of disease, in majority of farmers, defies the phenomenon of “Hygiene Hypothesis”, focusing on the role of epigenetic changes and various outdoor allergens in the development of allergic rhinitis in them.

Introduction

Allergic Rhinitis (AR) is a disease characterized by paroxysmal sneezing, rhinorrhea and nasal blockage, due to Type-1 hypersensitivity reaction to an inhalant allergen [1]. AR is mostly a clinical diagnosis and investigations like serum IgE estimation and Skin Prick testing are still not universally available investigation [2]. It has become the pandemic of modern era, with growing concern in Indian subcontinent, and other developing countries, due to social and health-related impacts [3]. AR is often coupled with various comorbidities, including bronchial-asthma and chronic sinusitis, chronic otitis media, obstructive sleep apnea and lower respiratory tract infections [4]. These conditions further increase the disease related health burden and patient morbidity. The rise in incidence of AR could be attributable partly to better diagnostic facilities in recent times, previous underreporting, and lack of awareness, or it could be a true increase in the number of cases, related to changing lifestyle and environmental conditions [3]. There is sparse data available related to AR from India, with a reported incidence of around 20–30% in the country, according to reports. [1]

The triggers for AR include pollens, molds, animal dander, dust, and other inhaled allergens. ARIA guidelines define Disease characteristics under “Severity” and “Pattern” of AR, as “Mild, Moderate or Severe” and “Intermittent or Persistent” [5], respectively. Similarly, Type of disease could be classified into Seasonal and Perennial [6], according to other classification. Various genetic and epigenetic factors related to patient, like atopy, environmental factors, occupation and the prevalence of allergens in the region, which are further dependent on the climatic variations, could influence the Disease characteristics [4]. Since the disease occurrence and characteristics, which include severity, pattern and type of the disease, are likely to depend on the patient characteristics like genetics (family history of atopy) and other demographic variables like age, gender and occupation, the current study was undertaken to see if there is any correlation between the disease characteristics and patient characteristics among patients with AR in rural central India. Allergic Rhinitis pathophysiology depends on patient characteristics, where genetics has a major role in occurrence of disease in atopic individuals. Similarly, patient demographics including age, gender, area of residence and occupation, which could influence various Epigenetic changes like the disproportion between the Th1/Th2 [7], alteration of the cytokine profile, raised IgE, and reducing the number of T regulatory cells that causes a dysregulation of the immune system’s response, have also been shown liable for the development of AR. [8]

Due to wide climatic variations and different prevalence of allergens, studies for understanding the pathophysiology of AR should be conducted in different environmental conditions and among different populations. There is scarcity of data on this from rural India and there is no uniformity in diagnosis of AR. The current study also aimed to find the allergen sensitivity pattern by Skin Prick Test, in patients with AR, and correlation of the most prevalent allergen sensitivity with patient characteristics like age, gender and occupation.

The disease occurrence and characteristics, which include severity, pattern and type of the disease are likely to depend on the participant characteristics like genetics (family history of atopy), and other variables like age, gender and occupation, which could influence their epigenetics, hence current study was undertaken to correlate the ‘disease characteristics’ with ‘participant characteristics or demographics.’ This study on patients from rural Central India, was undertaken to facilitate better understanding of the disease pathophysiology.

Our study which correlates the patient characteristics with disease characteristics has relevance with regard to providing a personalized treatment approach as advocated by ARIA-NEXT guidelines [9]. This would also help in deciding and devising protocols in AR management, incorporating the patient characteristics as a basis for person-centric treatment approach.

Material and methods

The Prospective Observational Study was conducted in the Otolaryngology Department of a tertiary care teaching hospital situated in the rural area of Wardha District. All the consecutive/sequential patients were in the age group of 10 years to 70 years. Prior approval from Institutional Ethical Committee DMIMS (DU)/IEC/Aug-2019/8233 was taken for the study and informed consent was taken from all the patients for inclusion in the study. The study was conducted over a period of 2 years starting 1st September 2019 to 31st August 2021 in 90 patients. SPSS 24.0 Version Graph Pad Prism 7.0 version was used for statistical analysis with the help of chi-square test. p value of < 0.05 was considered statistically significant.

All the consecutive/sequential patients between 5 and 70 years of age presenting with nasal complaints, diagnosed with allergic rhinitis, regardless of gender and ethnicity, and presenting to ENT outpatient department, ENT ward or casualty were included in the study. The detailed methodology followed was, as depicted in the Flow chart.

Methodology

Subjects were studied for their disease characteristics including severity and pattern of allergic rhinitis by ARIA guidelines type of allergic rhinitis and common allergens [5]; severity and pattern of AR in terms of mild / moderate—severe, intermittent / persistent type of AR in terms of seasonal and perennial [6], were correlated with patient characteristics like age, gender, occupation, family history of atopy etc. Skin Prick test was the technique for the identification of common allergen sensitivities [10, 11], by making pricks with lancet on Forearm/ back, using a kit of total of 150 allergens common in the region of rural central India. (Figs. 1,2) Color coding was done for different allergen, as shown in Fig. 2. The information was entered in a predesigned proforma. SPT results were graded as following:

Fig. 1.

Methodology flow chart

Fig. 2.

Allergen kit with color coding according to the type of allergens. (yellow-molds, green-pollens, orange-house dust allergens, white-histamine and control. Brown-food allergens, pink cockroach, insect, blue-animal dander.)

Observation and results

• IPatient characteristics:

Majority of the patients were in the age group of 16–40 years and males (63.33%) outnumbered females. 43.33% patients in our study had a positive familial history of atopy. Majority of the participants were Medical Professionals (46.66%) and 17.77% farmers, as depicted in Tables 1, 2.

• IIDisease characteristics.
  1. Distribution of patients according to pattern and severity of allergic rhinitis (ARIA GUIDELINES). [5]
• 2Distribution of allergic rhinitis patients according to Type of AR: [6]

Majority (79.99%) of the patients had moderate to severe type of the disease as shown in Table 3.

Table 1.

Severity of allergic rhinitis

Grading	Diameter
-ve	< 2mm
±	< 3mm
+	3-5mm
+  +	< 6mm
+  +  +	> 6mm
+  +  +  +	> 6mm with pseudopodia

Table 2.

patient characteristics

Profile	Number %
Age
5–16 years	7 (8%)
16–40 years	71 (79%)
> 40 years	12 (13%)
Gender
Males	57 (63.33%)
Females	33 (36.66%)
Occupation
Farmer	16 (17.77%)
Housewife	14(15.55%)
Medical Professionals
Shopkeeper	42 (46.66%)
2 (2.22%)
Labourer	13 (14.44%)
Medical professional	2(2.22)
Fruit vendor	3(3.33%)
Familial history of atopy
Positive	39 (43.33%)
Negative	51 (56.66%)

Table 3.

Distribution of patients according to pattern and severity of allergic rhinitis

Severity and pattern of AR	No of patients
Mild intermittent	10 (11.11%)
Mild persistent	8 (8.88%)
Mod-severe intermittent	26 (28.881)
Mod-severe persistent	46 ((51.11%)
Total	90

Majority of the patients had perennial type of disease. As depicted in Table 4.

• IIICorrelation of patient characteristics with disease characteristics:

• • 1) Correlation of pattern and severity of allergic rhinitis with age (According to ARIA guidelines). [5]
    In 16-40 years of age group, moderate to severe form of disease was found in majority of the patients. As depicted in Table 5.
  • 2) [6] Correlation of type of allergic rhinitis with age.
  • 3) Perennial type of disease was common in middle age population (16–40 yrs.) As depicted in Table 6.
  • 4) Correlation of pattern and severity of allergic rhinitis with occupation (According to ARIA guidelines). [5]
    45.52 % medical professionals belonged to the category of moderate to severe type of
    Allergic Rhinitis, similarly 71.43 % housewife had moderate to severe type of AR. 52.94 % of farmers had moderate to severe type of the disease. (as depicted in Table 7)
  • 5) Correlation of type of allergic rhinitis with occupation [6]
    43.90% Medical professionals showed seasonal type of allergic rhinitis and 56.10% were of perennial type. years, similarly 26% farmers had seasonal and 74% perennial type of AR. Mite was the commonest allergen in medical professionals and pollens was found to be common in farmers. As depicted in Table 8.
  • 6) Correlation of type of allergic rhinitis with family history in the age between of 16 to 40 years. [6]
    68.42% patient had a positive family history of atopy, 38% patients had negative family history of atopy. As depicted in Table 9, Perennial type was more common in patients with positive family history of atopy with statistically significant value.

• IV Allergen sensitivity detected on SPT.

Table 4.

Distribution of allergic rhinitis patients according to Type of AR:

Type of AR	No of patients
Seasonal	39(35.09%)
Perennial	51(64.91%)
Total	90
ϗ2-value	4.30, p value = 0.030, Significant

Table 5.

Correlation of pattern and severity of allergic rhinitis with age

Age	Mild intermittent	Mod-severe intermittent	Mild persistent	Mod-severe persistent	Total
5–16 yrs	0	1 (1.11%)	1 (1.11%)	5 (5.55%)	7 (7.77%)
16–40 yrs	8 (11.26%)	20 (28.16%)	8 (11.26%)	35 (49.29%)	71 (79%)	p = 0.00001
> 40 yrs	3 (3.33%)	4 (4.44%)	0	5 (5.55%)	12 (13.33%)

Table 6.

Correlation of type of allergic rhinitis with age

Age	Seasonal	Perennial	Total
< 16 yrs	8	5	13
16–40 yrs	26	38	64
> 40 yrs	6	7	12
Total	39	51	90
ϗ2-value	11.06, p-value = 0.08, Not Significant

Table 7.

Correlation of pattern and severity of allergic rhinitis with occupation (According to ARIA guidelines) [5]

Age	Mild intermittent	Mod-severe intermittent	Mild persistent	Mod-severe persistent	Total
Medical professional	4(9.52%)	4(7.14%)	16(38.10%)	19(45.24%)	43(46.67%)
Farmer	3(17.65%)	2(11.76%)	3(17.65%)	9(52.94%)	17(18.89%)	p = 0.68
HW	1(7.14%)	1(7.14%)	2(14.29%)	10(71.43%)	14(15.56%)

Table 8.

Correlation of type of allergic rhinitis with occupation and common allergens

	Seasonal	Perennial	Total	Common allergen on SPT
Medical Professionals	18(43.90%)	24(56.10%)	42(45.56%)	Mite
Farmers	4(26.67%)	11(73.33%)	15(16.67%)	Molds Pollens
Housewife	7(50%)	7(50%)	14(15.56%)	Mite
Labourer	6(50%)	6(50%)	12(13.33%)	Molds and mites
Shopkeeper	0(0%)	2(100%)	2(2.22%)	Mite
Fruit vendor	1(33.33%)	2(66.67%)	3(3.33%)	Mite
Total	39(43.33%)	51(56.67%)	90(100%)
ϗ2-value	5.94, p = 0.42, NS, p > 0.05

Table 9.

Correlation between type of allergic rhinitis with family history in the age between of 16 to 40 years

	Familial history of atopy
	Positive	Negative
Perennial	20(76.92%)	5(20%)
Seasonal	6(23.07%)	7(53.85%)
Total	26(68.42%)	12(38%)
ϗ2-value	4.53, p = 0.033, Significant

On meticulously examining the patients, they showed sensitivity to various allergens. As depicted in Table 10, the most common allergen sensitivity was found to be for mites 68 (75%) followed by dust in73.33%. The patients revealed aggravation of rhinorrhea and sneezing on exposure to irritants like dust, cleaning bedsheets and traditional cooking like chulha [4].

Table 10.

Allergen sensitivity detected on SPT

Type of allergens	No of patients	Percentage
Cynodome	16	17.77
Parthenium	16	17.77
Mite	68	75.55
Dander	24	26.66
Dust	66	73.33
Candida	7	7.77
Aspergillus	33	36.66
Xanthium	11	12.22
Chenopodium	15	16.66
Rhizopus	9	10

Discussion

The present study has attempted to correlate the disease characteristics with patient characteristics with aim of identifying the likely role of genetic and epigenetic factors in pathophysiology of AR, which would help us in better understanding of pathophysiology of AR and also form a basis for personalized treatment protocols, as advocated by ARIA next guidelines. [9]

Ninety patients with clinically confirmed A.R. were chosen for this study, and demographic data and data related to Allergen exposure, occupation and family history were considered.

Majority of the patients of AR belonged to the age group of 16–40 years. Singhvi et al. in their study had similar findings [12]. Moderate to severe form of disease was found in majority of the patients in this age group (77%) and this was found to be statistically significant. Majority (59.37%) of the patients in the age group of 16–40 years had perennial type of disease. On the other hand, seasonal type of allergic rhinitis was common in age group of less than 15. To the best of our knowledge we could not find any study which has correlated the severity and type of AR with the Age group. Alyasin and Amin [11], had proposed that classification of AR into Seasonal and Perennial is different from Persistent and Intermittent [13]. Accordingly, we have studied both these features separately under Disease Characteristics.

Most of the patients with AR were Medical Students (46.67%), followed by Farmers (17.77%) and housewives (15.55%). Medical students (52%) suffered from moderate to severe type of Allergic Rhinitis, with Persistent disease in approximately 80%. Similarly, 70.59% of farmers had moderate to severe type of the disease, with persistent disease in 70%. 56.10% medical professionals showed seasonal type of allergic rhinitis and 43.90% were of perennial type. years, similarly 26% farmers had seasonal and 74% perennial type of AR. Taking into account allergen sensitivity, farmers were mainly sensitive to Molds and Pollens, whereas medical professionals were found to be sensitive to Mites. The more frequent occurrence of persistent and perennial form of disease among farmers emphasizes the duration of exposure as the key factor apart from the family history of atopy in them, as farmers mainly work under pollens and molds in the farm. Similarly, frequent occurrence of persistent form of disease among medical students is due to constant exposure to indoor allergens like mites. We could not find any study relating the occupation of the patient with the type of allergen sensitivity or to have correlated the severity and pattern of AR with the profession. If the hygiene hypothesis held true, allergy should not have been found in farmers [14], however significant number of patients still had the disease, so this may be because of the epigenetic changes that are related to the environmental factors and also due to persistent exposure to allergens which they may be sensitive to.

As the study was conducted in medical college setup majority of the patients were medical professionals, so we focused on this group and further careful evaluation revealed,70% had strong family history signifying the role of atopy in them. In our study, more than 50% of patients were without family history of atopy, which emphasizes the role of environmental factors leading to epigenetic changes in them. The perennial type of allergic rhinitis was more common among the patients with positive family history of atopy with statistically significant correlation between the perennial type of AR and positive family history of atopy. Environmental factors like pollen, dust with persistent duration of exposure, along with atopy have synergistic role in the development of allergic rhinitis [15]. Both perennial and seasonal type of allergic rhinitis were equally distributed in non-atopic (50%) individuals. [6]

In our study, a high occurrence of male patients was found with a sex ratio being 1.7:1 which can be explained as males being the main bread earners in this country are at greater risk of exposure to aeroallergens. Similar findings have been reported by several other authors as well. [12, 13] 78.56% of male patients suffered from moderate to severe form of disease and 21.44% of males had mild form of disease. This highlights the fact that more severe form of the disease is found in the males. As the group is more outgoing and social, hence various environmental factors like pollution and epigenetic changes could be contributory towards occurrence of AR.

Allergen sensitivity detected on SPT.

In this study we tried to find common allergens in the patients with the help of SPT.

We found the mite to be the most common allergen seen in 75% of the patients, followed by dust in 73.33%. 36.66% of patients were allergic to Aspergillus, and most had a seasonal type of allergic rhinitis. These patients had aggravated symptoms during the winter and rainy seasons. The fourth most common allergen was animal dander which was seen in 26.66% of them.

The majority of house dust allergies result from the house dust mites (HDM) such as Dermatophagoides pteronyssinus (American house dust mite), Dermatophagoides farinae, Dermatophagoides microceras, and (Mayne's house dust mite). Euroglyphus maynei lives on skin flakes; thus, they are frequently found in mattresses, beds, and stuffed animals. HDM (House dust mite) are present throughout the year. However, they are at their highest during humid periods. Animal dander—Cat and dog dander are the most prevalent animals whose dander causes allergic reactions. Dander from rodents or horses could potentially cause allergic reactions. Molds- Four different Molds cause allergic rhinitis symptoms [16]. Aspergillus, and candida are the most common organism found in spoiled food and often in damp areas and spoiled food. In our study we found them common in seasonal type of AR.

Table 11 showing common allergens detected on SPT by various studies in India.

Table 11.

Comparative studies of common allergens in India

Type Of allergen	Present study	Other study
House dust	73.33%	26% Singhvi et al [12]
35% Animesh et al. [17]
MITE	75.55%	45% Animesh et al [17]
Animal dander	26.66%	6% Singhvi et al [12]
37.2% Animesh et al. [17]
Aspergillus	36.66%	116 (52.4%] Animesh et al. 17

Preventive measures

Aesthetics related to Interior designing should be modified in view of increasing prevalence of allergic rhinitis. Various preventive measures like daily vacuum cleaning, keeping mattresses and blankets on terrace or balcony for exposure to sunlight will help in killing the mites. Similarly, detachable Interiors, mattresses in sofas and bed should be encouraged so that proper cleaning can be given to them.

Due to increased civilization, overcrowding, lack of awareness of people regarding proper ventilation and exposure to sun caused increasing trend of allergic rhinitis [18]. Based on sociodemographic factors mainly in younger age group, the local fauna prevalent in the region, their pollinating season and person’s individual sensitivity to a particular allergen may be the predominant factors responsible for the occurrence of AR in them. Personal factors related to the indoor mite prevention measures for maintaining a clean and non humid environment with proper ventilation may help to reduce the exposure of susceptible individuals to get sensitized.

Allergen avoidance measures should be advocated for Mite sensitive individuals and those with the perennial form of A.R., which include daily vacuum cleaning, keeping mattresses, and blankets in terraces and balconies for exposure to sunlight, Aesthetic modifications related to Interior designing, like detachable Interiors, and cushions on sofas.

Environmental modifications like cutting trees to which the majority of individuals are sensitive and anti-pollinating measures, wherever feasible, will help in the prevention of early sensitization of individuals in that area.

We propose the role of various environmental factors, leading to epigenetic changes, to significantly contribute to the development of Allergic Rhinitis in recent times [8, 19]. The occurrence of Allergic rhinitis between the group of 16–40 years in a severe and perennial form, that too in patients without a family history of atopy [13], occurring in rural population, who are more exposed to various allergens since childhood, defies the hygiene hypothesis to some extent and highlight the possible role of epigenetic changes [8, 19], being a significant contributor for a rise in prevalence of A.R. in this region.

Conclusion

Severity and type of AR can be correlated with occupation, which has relevance related to type and duration of allergen exposure. In our study we observed that disease characteristics were related to patient characteristics, as evident from the fact that in farmers and medical professionals, persistent form of disease was common due to long duration of exposure to respective allergens, hence we propose that “Disease characteristics” as per ARIA Guidelines should not be taken in isolation and “Patient characteristics” viz. Age, Occupation, Family history of atopy, should be considered in management of AR for devising protocols.

The perennial type of allergic rhinitis was more common among the patients with positive family history of atopy, with statistically significant correlation between the perennial type of AR and positive family history of atopy. Hence, both atopy and duration of allergen exposure have contributory role in causation of severe and persistent form of disease. This is probably the first study correlated disease characteristics with patient characteristics.

In our study, more than 50% of the patients were without family history of atopy, which emphasizes the role of environmental factors leading to epigenetic changes in them. Reversing or targeting the epigenetic changes in susceptible individuals can help prevent sensitization of the individual and better treatment outcome in patients with AR, help cure the symptoms without drug dependence.

Mite is a major contributor as Indoor allergen, detected on Skin Prick Test.

Limitations

As the study was conducted in a tertiary care hospital, the sample may differ from the true representative of the community in this area; further studies need to be carried out in the community base population for a more accurate understanding of the disease.

Funding

The authors did not receive support from any organization for the submitted work.

Declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.