Allergy in India

India has recently overtaken China as the most populous country in the globe with an estimated total population of ~1.43 billion people, comprising approximately 20% of the globe. India is classified as a Low-Middle Income Country (LMIC) by the World Bank, and the nation shows great diversity and some sharp contrasts with high-income countries (HICs). Religion and culture, rural–urban divide, infectious disease burden, diet, breastfeeding, allergen and pollutant exposure all differ in India compared with HICs and are relevant to allergy. Most of our current knowledge regarding aetiopathogenesis and therapeutics in allergic disease has been generated from research conducted in HICs but the emerging data on allergic disease in India and other LMICs are fascinating. Striking features of allergy in India include very low rates of childhood eczema, asthma and food allergy but a high burden of drug allergy and allergic bronchopulmonary aspergillosis and diverse triggers of allergic rhinoconjunctivitis. We are, therefore, delighted to present this special issue of Clinical and Experimental Allergy, which summarises key insights related to Allergy in India. A wide range of topics have been covered by leading experts from India including indoor and outdoor allergens, allergic airways disease, allergic bronchopulmonary aspergillosis (ABPA) and food allergy. Laha et al. dissect the very complex nature of indoor and outdoor allergens (83 pollens, 34 fungi, six dust mite) that are of relevance to the Indian population.1 Given the large cross-sectional geographical area of the country with some contrasting climatic conditions between north–south and east–west, they identified commonalities and differences in aeroallergens and highlight cross-reactivity between pollens, dust mite and fungi.1 However, as allergy practice in India is still in its infancy, there are major challenges in standardising allergen panels for testing and establishment of allergens in immunotherapy extracts for the treatment of allergic airways disease. The subject of global warming has attracted great interest in recent years as India produces 7% of greenhouse gases (3619.8 million tonnes in 2018), third after USA and China, and levels of PM2.5 in metropolitan cities such as New Delhi, Kolkata and Mumbai are amongst the highest in the world.2 Higher levels of carbon dioxide enhance photosynthesis and pollen production and alter flowering pattern.3 Pollens are contained within PM2.5 and a combination of global warming and PM2.5 (and other pollutants) may augment the adverse impact on allergic airways disease.3 Global warming causes early pollination and prolongs hay fever season, enhances pollen burden and alters allergenicity.3 Moitra et al. highlight the high burden of allergic rhinitis in India, although they recognise the limitations of published evidence.4 Existing data suggest a very high rate of sensitisation to dust mites including Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis. The authors highlight the potential role for other environmental triggers that are unique to India (and probably other countries in the Indian subcontinent) including open dumpsters, a source of biodegradable and non-biodegradable waste, bacteria, toxins and fungi and serious biohazards such as open disposal of sanitary napkins and diapers. Therefore, an important question that follows is whether non-allergic rhinitis due to other noxious agents as stated alters the natural course of allergic rhinitis, as this may have potential implications with respect to response to first-line pharmacotherapy and allergen-specific immunotherapy and biologic agents. This calls for well-designed multi-centre studies in allergic rhinitis and asthma in the native Indian population, and evidence from clinical trials conducted in HICs must not be directly extrapolated for shaping local and national policies. Agarwal et al, estimate the community prevalence of ABPA as 46.2 per 100,000 population in India, probably highest in the world, with a greater burden in rural compared to the urban community.5, 6 They estimate that there are approximately 1.4–1.9 million cases of ABPA in India.5 ABPA patients in India present at a younger age with a relatively higher serum total IgE and the authors link ABPA to genetic predisposition and environmental factors and highlight the need for further research.5 The authors conducted a survey amongst clinicians involved in the management of asthma in different healthcare sectors and highlight the heterogeneity in the diagnosis and management with a need to standardise clinical practice.5 There are important challenges with respect to access and affordability to test for aspergillus sensitisation and relevant biomarkers, particularly in the rural and public sector. A cost-effective avenue for ABPA screening in the community might be to look into the feasibility of rapid aspergillus IgE testing using capillary blood on a test strip. Interestingly the prevalence of clinically relevant food allergy is very low in India compared to HICs. Mahesh et al. highlight a very interesting observation made in the EuroPrevall-INCO study that showed a very high sensitisation rate to food allergens, as evidenced by serum-specific IgE.7 The prevalence of sensitisation to common food allergens was 20% and 25% in children and adults in Karnataka, a southern Indian state, although ‘probable allergy’ was just about 0.14% and 1.2%, respectively.7 There are no published data from other Indian states. These data raise some important research questions. First, ‘Is the high sensitisation merely due to aeroallergen-related cross-reactivity?’ Further studies employing component-resolved diagnostics may shed light. This will confirm whether or not sensitisation seen to whole allergens are related to sensitisation to PR-10, storage proteins and/or lipid transfer proteins. Second, ‘Are there significant immune tolerance mechanisms in play, such as regulatory T cells or blocking antibodies that protect sensitised individuals from being clinically reactive?’ Third, ‘Is there a rural-urban divide with respect to food allergy, as reported for allergic rhinitis and asthma?’ Fourth, ‘what are the protective factors which inhibit the development of clinical reactivity to food allergens in India?’ These appear to be lost when families migrate to HICs,8 and epidemiological studies involving native and immigrant populations might help shed light on protective factors and pave the way for primary and secondary prevention measures. Figure 1 illustrates a model of gene–environment interplay for atopy and allergy in India based on current evidence. The experts that contributed to this special edition recognise an urgent need for addressing the huge gap in postgraduate specialist training in allergy in India and for the establishment of a robust framework to deliver standardised and equitable healthcare to people living in India who suffer with allergic conditions.9 Clearly, this needs a joined-up approach between multidisciplinary healthcare professionals, policymakers, national scientific societies, and local governments. From a research viewpoint, India presents an invaluable opportunity to learn about new disease phenotypes and clusters in varied ethnic populations and to improve our current understanding of the aetiology of allergic diseases. MTK drafted the manuscript. MS and RJB reviewed the manuscript and approved final version. MTK secured research funding from NIHR, MRC CiC, FSA and GCRF for work outside this manuscript. His department in University Hospitals Birmingham NHS Foundation Trust received educational grants for annual PracticAllergy course from pharmaceutical companies including ALK Abello, Allergy Therapeutics and MEDA. MTK is participating in a Delphi Advisory group organised by ALK Abello regarding allergen-specific immunotherapy pathways. RJB declares research support from NIHR, personal fees for editorial work from Wiley, Cochrane and the British Society for Allergy and Clinical Immunology and personal fees for medicolegal work related to food allergy and eczema.