|Year : 2021 | Volume
| Issue : 2 | Page : 82-87
Self-reported food allergy and its clinical significance in adult bronchial asthma patients:– A prospective study
Priya Sharma1, Bharath Janapati2, Rachna Rohatgi3, Anil Kumar Jain4
1 Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, Patna, Ex DNB, India
2 Department of Pulmonology, Virinchi Hospitals, Hyderabad, Ex DNB, NITRD, India
3 Department of Anatomy, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
4 Department of TB and Respiratory Diseases, National Institute of TB and Respiratory Diseases, New Delhi, India
|Date of Submission||29-Dec-2020|
|Date of Acceptance||01-Jan-2022|
|Date of Web Publication||08-Jul-2022|
Dr. Anil Kumar Jain
Room No. 203, 2nd Floor, OPD Building, National Institute of TB and Respiratory Diseases, Sri Aurobindo Marg, Near Qutub Minar, Mehrauli, Delhi - 110 030
Source of Support: None, Conflict of Interest: None
BACKGROUND: Self-reported food allergy is very common in asthmatics and hence these food items are frequently avoided by the patients. Food allergy is defined as an adverse immunological response to a dietary protein. Skin prick test (SPT) is a sensitive tool for identifying the presence of specific immunoglobulin E antibodies that can be associated with acute allergic reactions. However, sensitization often exists without clinical consequences, and at the same time, self-reported food allergens are frequently negative on SPT. The purpose of our study was to assess the clinical relevance of self-reported food allergy and the role of SPT in identifying food allergies in patients with bronchial asthma.
METHODOLOGY: One hundred bronchial asthma patients were screened for this study, and skin prick testing for 22 food allergens frequently consumed in India, particularly Northern India was performed.
RESULTS: A total of 36 subjects reported perceiving precipitation or an increase in severity of the asthmatic symptoms by one or more food items, and the most common food items mentioned in history were curd in 24%, rice in 19%, citrus fruits such as lemon in 14%, orange in 14%, banana in 8%, cold drinks in 16%, and ice creams in 16%. There were 68 patients negative for food allergens by SPT (food allergen negative [FAN] group) and 32 patients were positive (Food allergen Positive [FAP] group). Out of 36 asthmatics with self-reported food allergy, none was found to be SPT positive to the reported food allergens. However, 50% of patients with self-reported and only 21.9% with no history of food allergy were positive to one or more food allergens. Further, FAP group patients were tolerating these foods without any trouble or exacerbation of symptoms. Among the FAP group, 96.9% of patients had positive SPT for one or more other allergens also such as insects, pollens, fungi, or other aeroallergens. Only one patient had isolated food allergy by SPT. It implies that isolated food allergy is very rare in asthmatic patients. Common food allergens found positive by SPT were black gram in 12%, followed by red gram 9% and bengal gram, rice, and Baker's yeast 7% each.
CONCLUSION: We concluded that the prevalence of food allergy in India among asthmatic adults though high, has a very poor correlation between patient's history of food allergens that is perceived as a precipitating or exaggerating factor for symptoms and actual sensitization as elicited by SPT. At the same time, there is high nonspecific food sensitization in self-reported patients as compared to those with no history of any perceived food allergy.
Keywords: Bronchial asthma, food allergy, self-reported, skin prick test
|How to cite this article:|
Sharma P, Janapati B, Rohatgi R, Jain AK. Self-reported food allergy and its clinical significance in adult bronchial asthma patients:– A prospective study. Indian J Allergy Asthma Immunol 2021;35:82-7
|How to cite this URL:|
Sharma P, Janapati B, Rohatgi R, Jain AK. Self-reported food allergy and its clinical significance in adult bronchial asthma patients:– A prospective study. Indian J Allergy Asthma Immunol [serial online] 2021 [cited 2022 Aug 19];35:82-7. Available from: https://www.ijaai.in/text.asp?2021/35/2/82/350084
| Introduction|| |
Johansson et al. proposed that an adverse reaction to food is called as food hypersensitivity. Food hypersensitivity can be further classified as food allergy (immunoglobulin E [IgE] and non-IgE mediated) and nonallergic food hypersensitivity. When immunologic mechanisms have been demonstrated, the appropriate term is food allergy and if the role of IgE is highlighted, the term is IgE-mediated food allergy. All other reactions, previously sometimes referred to as “'food intolerance,” should be referred to as nonallergic food hypersensitivity. Severe, generalized allergic reactions to food can be classified as anaphylaxis. Hence, food allergy is an abnormal or exaggerated immunologic response to specific food protein. It may be IgE mediated with rapid onset of action or nonIgE mediated which takes hours to produce symptoms.
Food hypersensitivity is estimated to be approximately 2% in adults and 8% in children. A high level of sensitization (26.5%) was observed for most of the foods in the general population of south India. Food-related reactions are associated with a number of clinical presentations that may involve many systems including the skin, gastrointestinal, respiratory tracts, and cardiovascular system. Although ingestion is supposed to be the cause, other modes of sensitization are inhalation and cutaneous route. Most asthmatic reactions to inhaled food allergens are described in occupational settings. In a group of 12 children with an IgE-mediated food allergy who developed asthma on inhalational exposure to food, the offending food was being cooked. Loss-of-function variants of the filaggrin mutation result in an impaired epidermal barrier function and have been shown to be a risk factor for the development of atopic dermatitis, allergies, and asthma.
Asthma and food allergy are frequently coexisting, and both are increasing in prevalence. In a survey of 156 patients attending asthma and allergy clinic, 73% of people believed that foods induced their asthma symptoms. A large German retrospective cohort study showed that food allergy was an important risk factor for developing asthma, with an odds ratio of 2.16. Roberts et al. even reported a higher rate; they showed that children with food allergies are around six times more likely to suffer from severe asthma later in life than children who did not have food allergies. Berns et al. reported that food allergy might be a risk factor for increased asthma morbidity in adults.
More than 20% of adults and children modify their diets due to perceived food allergy, and hence it is important to distinguish food allergy from other nonimmune-mediated adverse reactions to foods.
The gold-standard method for diagnosing food allergy/intolerance is double-blind placebo-controlled food challenge tests. The test is laborious and difficult to test all combinations of food types that may be causing symptoms. Other tests include skin prick test (SPT), atopy patch test, and serum food-specific IgE.
SPTs are safe and useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions. SPT is extremely sensitive and has a negative predictive value of >90%. It helps in ruling out an IgE-mediated food allergy rapidly. It also helps to confirm a food allergy when positive, in the setting of a clear history of an acute allergic reaction to the tested food (high prior probability). Unfortunately, the specificity of skin testing is <50%, and a positive test is able to confirm sensitization to an allergen but does not confirm a diagnosis of food allergy. Sensitization often does not equate to clinical allergy and can lead to unnecessary food avoidance.
In this study, we assessed the clinical significance of SPT for food allergens in adult bronchial asthma patients, especially in relation to self-reported food allergy.
Study population included adults (n = 100) in the age range of 15–55 years with perennial asthma, i.e., patients had symptoms which were chronic, persisting round the year, and they may show up intermittently throughout the year.
With or without comorbidities, diagnosed on the basis of four cardinal respiratory symptoms and clinical history (episodic breathlessness, chest tightness, cough, and wheezing) and/or by degree of reversibility in forced expiratory volume in one second of 12%, and 200 ml from the prebronchodilator value (GINA 2016 guidelines).
Bronchial asthma patients referred to Allergy and Immunotherapy Unit, National Institute of TB and Respiratory diseases, New Delhi were included in the study during 2016–2018.
Pregnant and lactating women, patients with generalized skin disease/dermographism, cardiac disease, patients not giving consent for SPT, and patients who are on treatment with drugs interfering with SPT and for those in whom these drugs cannot be stopped for the SPT were excluded from the study.
| Methodology|| |
From 231 patients referred to Allergy and Immunotherapy Unit, 60 patients were having seasonal exacerbations, 17 refused for SPT, 15 patients were pregnant or lactating, 24 patients complained of giddiness during SPT but not amounting to anaphylaxis and further procedure was abandoned, 5 patients were already on treatment for eczema or had significant dermographism, and 10 patients were on cardiac medications (beta-blocker and angiotensin-converting enzyme inhibitors). These patients were excluded, and finally 100 bronchial asthma patients were enrolled as per inclusion and exclusion criteria. A detailed history including food allergy was recorded, and chest radiograph, spirometry, and blood analysis were performed. They were further subjected to SPT for 22 commonly consumed food items that also included self-reported food allergens in Northern India and to 60 other nonfood allergens (insects, fungal, and aeroallergens). All precautions were taken to manage any potential incident of anaphylaxis. The allergens were procured from All Cure Pharma Pvt. Ltd. Haryana, India.
Antigen extract-1: 10 concentrations in glycerinated buffer saline.
Histamine diphosphate in glycerinated buffer saline (1 mg/ml) and glycerinated buffer saline were used as positive and negative controls, respectively.
Site of application
The sites used for SPT were the volar surface of the forearm, upper arm, and back. On the volar surface, the area used for testing was 5 cm above wrist and 3 cm below antecubital fossa.
Position for testing was marked by numbers on skin to identify the allergen, and prick was made just adjacent to the number. Allergens were kept 2 cm apart to avoid overlapping between reactions. Allergen was applied in the form of drop followed by prick. A lancet or needle (26G) was used for prick, holding at 45° to skin. After prick, skin was raised with lancet for the proper exposure of allergen to skin mast cells.
Grading system for skin prick test
A positive result (2 + and above) to a specific antigen is indicated by a mean wheel diameter measuring 3 mm or more, greater than negative control.,
The study protocol was approved by the Human Ethics Committee of the Institute, and written consent was obtained from all patients.
After collection of data, it was checked, cleaned, edited, and verified daily to exclude any error and inconsistency. The data have been presented as numbers with a percentage (frequency) or mean with standard deviation as appropriate. Student's t-test was performed to compare continuous variables. The significance of the difference between the proportions of qualitative characteristics has been tested using Chi-square test (of independent of attributes).
The study subjects positive and negative for food allergens by SPT were compared using Chi-square test. A P < 0.05 was considered statistically significant.
| Results|| |
A total of 100 bronchial asthma patients were recruited for the current study. These included 65 males and 35 females. The subjects belonged to the age group of 15–55 years. Thirty-six patients (23 males [63.8%] and 13 females [36.2%]) gave a history of food allergy. All enrolled asthmatics gave a history to more than one food allergen and none of them specified a single food allergen for exacerbation or precipitation of his/her symptoms.
Asthma precipitation/exacerbation was frequently reported among 36 (36%) patients. The most commonly reported food items by asthmatics were curd by 24%, rice by 19%, citrus fruits such as lemon by 14%, orange 14%, banana in 8%, raddish 2%, tomato in 1%, egg in 1%, and fish in 1% of patients. Nonspecific food items were also reported along with the above food allergens such as cold drinks in 16%, ice creams in 16%, and oily/fried foods in 3% of patients but could not be tested by SPT.
On SPT, 68 patients were found to be (FAN group) and 32 patients were found to be food allergen positive (Food allergen Positive [FAP] group). The average age in the FAP group was 30.25 years, and the FAN group had an average age of 32.58 years. The prevalence of food allergen positivity was higher in male 23 (35.3%) as compared with female 9 (25.7%) asthmatics. Mean absolute eosinophil count and mean total IgE in both the groups were not statistically significant [Table 1].
|Table 1: Demographic and clinical details of patients in food allergen positive and food allergen negative group|
Click here to view
The food allergen positivity rate was seen to be decreasing as age increases, starting from 41.7% in the age group of 15–25 years to 15.4% in the age group of 46–55 years, although these data were statistically not significant [Table 2].
Out of total 36 patients with self-reported food allergy, 18 (50%) were positive by SPT, while only 14 (21.9%) were positive in patients with no self-reported food allergy. Hence, patients with no self-reported food allergy are likely to have negative SPT (78.12%) for any food allergies also [Table 3]. However, none of the subjects with SPT positive for any food allergens showed positivity to the food allergens as reported by the patients.
|Table 3: Skin prick test results in asthmatics with self-reported food allergy|
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Out of 32 SPT-positive patients in the FAP group, 31 (96.9%) patients had positive SPT for 1 or more nonfood allergens also such as insects, pollens and fungi. Among FAP group patients, 28 (87.5%) were positive to various pollens, 22 (69%) to insect allergens, and 10 (31%) were positive with one or more fungal extracts. Only one patient had isolated food allergy namely to chicken as demonstrated by SPT, but the patient was a vegetarian, so history of food allergy could not be elicited. It implies that isolated food allergy in asthmatics is very rare [Table 4].
SPT positivity among 32 patients of FAP group is given in [Table 5]. Maximum was with black gram (Urad dal) 37.5%, followed by red gram (Arhar dal) 28.1%, bengal gram 21.8%, rice 21.8%, and Baker's Yeast 21.8% and chicken 15.6%. The overall positivity among all asthmatics will be same as the number of each allergen because cases enrolled were 100.
| Discussion|| |
In India, perception of allergy to certain foods is more common than actual food allergy and varies across India according to local cultures and beliefs. In our study, 10 patients with perennial asthma were enrolled.
In our study, self-reported food allergy by asthmatics was 36% which is almost half as reported by Wood et al. We did not find any correlation between self-reported food allergens and positive SPT; it can be false negative or could also be because of change in allergenicity during digestion. Because of the low PPV of self-reported symptoms and lack of pathognomonic signs on physical examination, the accurate diagnosis of IgE-mediated food allergy should be aided by allergy testing including skin prick and/or serum IgE testing. In the Tucson Arizona study, it was shown that greater prevalence occurred among children and teenagers as compared to older adults. The results of our study are also consistent with the above study showing a decrease in food allergen positivity as the age advances. A negative SPT result does not rule out food allergy. The commercial extracts of fruits and vegetables are sometimes inadequate because the responsible allergen may be labile and altered during processing. In a study of children with food allergies, concordance between skin testing and challenge was 59% for commercial extracts and 92% for fresh food.
Sharman et al. conducted a study on 64 children (32 each in study and control group). Oral food challenge was administered to children to confirm or rule out the sensitivity of food (s) incriminated on the basis of the clinical history and/or a positive skin test. The study showed that even though food restriction (cold aerated drinks, curd, banana, rice, potato, black bean, and kidney bean) is a common practice in patients with respiratory allergy in India, objective documentation of Type I reactions due to these foods cannot be obtained in the majority of cases.
In our study, 32% of asthmatic patients though sensitized to different food allergens, were tolerating the same food without any symptoms of clinical allergy. The general sensitivity and specificity of skin prick testing for the diagnosis of food allergy is often estimated to be > 90% and approximately 50%, respectively. Thus, a positive SPT simply correlates with the presence of serum IgE bound to the surface of cutaneous mast cells, and in the clinical setting may lead to overdiagnosis of food allergy. Liu et al. reported that 27.5% of asthmatics had sensitization to at least one food item by measuring specific IgE levels, 1.9% were categorized as those likely to have a clinical food allergy, and 19% had levels that suggested unlikely for food allergy. In the clinical setting, when compared with oral food challenges, SPTs have high sensitivity and high negative predictive values. One interesting point observed in our study was that patients who perceived foods as precipitating/aggravating factor of the asthmatic symptoms showed higher chance of SPT positivity to food allergens although different from self-reported food allergens, as compared to those without any such history (50%vs. 22%). The clinical relevance of this difference in asthmatics is not known. Cross-reactivity among the similar group of food allergens is well known. A “positive” allergy test to a related food may simply represent immunologic cross-reactivity due to the presence of a homologous protein that does not have clinical significance, which is more common than true clinical cross-reactivity. Peanut is a prototypic example of an allergenic source material to which many people have IgE antibodies, but they can freely consume peanuts. Finding IgE to peanuts in peanut tolerant subjects is particularly common among pollen-sensitized patients. This association is due to IgE cross-reactivity between allergens from pollen and (glyco-) proteins in peanut and other vegetable sources.,
Isolated food sensitization or allergy was almost nonexistent in bronchial asthma patients in our study, i.e., almost all patients in FAP group had a coexistent sensitization to nonfood allergens, especially pollen sensitization which was seen in 87.5% Rajkumar et al. reported 35.5% of patients were SPT positive to one or more pollen extracts among food sensitized cases (history and SPT positive). Pollen sensitization can be sensitizing agents for many forms of plant food allergy. LiliKazemi-Shirazi et al. observed that each of the 71 patients included in his study, primarily on the basis of a clinically relevant food allergy, had an allergy to at least one pollen species.
Sensitization to one or more food allergens was seen in 32% bronchial asthma patients in our study, which is comparable with the study done by Rajkumar et al. In earlier studies. Black gram was found to be a common food item in the Indian population for which patients are sensitized and still consuming it without developing any hypersensitivity reaction. In our study also Black gram was the most common food allergen on SPT.
| Conclusion|| |
Patient's perception of food allergy to a food is not well correlated with a SPT for that particular antigen. Hence the physician should consider the skin test results in combination with the symptoms and physical examination. An asthmatic patient should not be advised to avoid foods which are well tolerated as it can lead to poor quality of life and malnutrition in severe cases. Patients without any history of food-related allergy are highly likely to be food SPT negative also. The common food items to which the food allergen test was positive in descending order were black gram, red gram, Bengal gram, Rice, and Baker's Yeast.
Limitation of study
One of the main limitations of our study was that only SPT was done to look for food allergen sensitivity and it was not compared with either Oral Food Challenge test, or the Double-Blind Placebo-Controlled Food Challenge test which have better sensitivity and specificity. A small sample size also adds up to this.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, et al.
A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001;56:813-24.
Bruijnzeel-Koomen C, Ortolani C, Aas K, Bindslev-Jensen C, Björkstén B, Moneret-Vautrin D, et al.
Adverse reactions to food. European academy of allergology and clinical immunology subcommittee. Allergy 1995;50:623-35.
Mahesh PA, Wong GW, Ogorodova L, Potts J, Leung TF, Fedorova O, et al.
Prevalence of food sensitization and probable food allergy among adults in India: The EuroPrevall INCO study. Allergy 2016;71:1010-9.
Waserman S, Watson W. Food allergy. Allergy Asthma Clin Immunol 2011;7 Suppl 1:S7.
Baur X. A compendium of causative agents of occupational asthma. J Occup Med Toxicol 2013;8:15.
Roberts G, Lack G. Relevance of inhalational exposure to food allergens. Curr Opin Allergy Clin Immunol 2003;3:211-5.
Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011;365:1315-27.
Woods RK, Weiner J, Abramson M, Thien F, Walters EH. Patients' perceptions of food-induced asthma. Aust N Z J Med 1996;26:504-12.
Hill DA, Grundmeier RW, Ram G, Spergel JM. The epidemiologic characteristics of healthcare provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: A retrospective cohort study. BMC Pediatr 2016;16:133.
Berns SH, Halm EA, Sampson HA, Sicherer SH, Busse PJ, Wisnivesky JP. Food allergy as a risk factor for asthma morbidity in adults. J Asthma 2007;44:377-81.
Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol 2010;125:S116-25.
Sampson HA. Food allergy. Part 2: Diagnosis and management. J Allergy Clin Immunol 1999;103:981-9.
Lieberman JA, Sicherer SH. Diagnosis of food allergy: Epicutaneous skin tests, in vitro
tests, and oral food challenge. Curr Allergy Asthma Rep 2011;11:58-64.
From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA); 2016. Available from: http://www.ginathma.org/
. [Last accessed on 2017 Jan 11].
Shivpuri DN. Comparative evaluation of the sensitivity of common methods of diagnostic antigen tests in patients of respiratory allergy. Indian Journal of Chest Diseases. 1962;4:102-8.
Bock SA, Lee WY, Remigio L, Holst A, May CD. Appraisal of skin tests with food extracts for diagnosis of food hypersensitivity. Clin Allergy 1978;8:559-64.
Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al.
Food allergy: A practice parameter update-2014. J Allergy Clin Immunol 2014;134:1016-25.e43.
Barbee RA, Kaltenborn W, Lebowitz MD, Burrows B. Longitudinal changes in allergen skin test reactivity in a community population sample. J Allergy Clin Immunol 1987;79:16-24.
Rancé F, Juchet A, Brémont F, Dutau G. Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy 1997;52:1031-5.
Sharman J, Kumar L, Singh S. Allergenicity of common foods restricted in respiratory allergy. Indian J Pediatr 2000;67:713-20.
American College of Allergy, Asthma, & Immunology. Food allergy: A practice parameter. Ann Allergy Asthma Immunol 2006;96:S1-68.
Saarinen KM, Suomalainen H, Savilahti E. Diagnostic value of skin-prick and patch tests and serum eosinophil cationic protein and cow's milk-specific IgE in infants with cow's milk allergy. Clin Exp Allergy 2001;31:423-9.
Sporik R, Hill DJ, Hosking CS. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy 2000;30:1540-6.
Liu AH, Jaramillo R, Sicherer SH, Wood RA, Bock SA, Burks AW, et al.
National prevalence and risk factors for food allergy and relationship to asthma: Results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol 2010;126:798-806.e13.
Sicherer SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001;108:881-90.
Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, et al.
EAACI molecular allergology user's guide. Pediatr Allergy Immunol 2016;27 Suppl 23:1-250.
van der Veen MJ, van Ree R, Aalberse RC, Akkerdaas J, Koppelman SJ, Jansen HM, et al.
Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins. J Allergy Clin Immunol 1997;100:327-34.
Kumar R, Kumari D, Srivastava P, Khare V, Fakhr H, Arora N, et al.
Identification of IgE-mediated food allergy and allergens in older children and adults with asthma and allergic rhinitis. Indian J Chest Dis Allied Sci 2010;52:217-24.
Kazemi-Shirazi L, Pauli G, Purohit A, Spitzauer S, Fröschl R, Hoffmann-Sommergruber K, et al.
Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy. J Allergy Clin Immunol 2000;105:116-25.
Kumari D, Kumar R, Sridhara S, Arora N, Gaur SN, Singh BP. Sensitization to blackgram in patients with bronchial asthma and rhinitis: Clinical evaluation and characterization of allergens. Allergy 2006;61:104-10.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]