The Climate Around and Within You: Environment, Epigenetics and Genetics Exploring Allergic Rhinitis

Sahana Kashyap

Today, many people find a safe haven in their homes. It is a trusted climate, especially following the pandemic years, where one’s well-being was seemingly ensured by avoiding exposure to external infections. However, the world now faces a different avenue of health concerns. As the hygiene hypothesis elucidates, there is a transition from infectious disease to allergies and auto-immune disorders. This new domain often has underlying genetic causes, and is influenced by environmental conditions. Individuals with sensitivity to different allergic reactions have especially felt such an impact. About 400 million people suffer from one such reaction affecting the nasal cavity, known as Allergic Rhinitis (AR) today. Their health condition, or the climate within them, is influenced by the climate around them.


In certain individuals, the body’s immune system overreacts to a typically harmless substance called an allergen, leading to a specific homeostatic imbalance known as an allergic reaction. Such individuals are most likely atopic, meaning that they are genetically predisposed to an allergic reaction due to these allergens. Allergens are a specific kind of antigen, or foreign substance, which triggers an immune response resulting in the production of antibodies: specific proteins that the body produces for protection from infections. Allergens, upon coming in contact with the skin, nose, eyes, and respiratory tract or gastrointestinal tract, elicit the response of a specific antibody, Immunoglobulin E (IgE). Some examples of allergens include pollen, latex, mold, pet dander, dust mites and smoke, and each individual, if susceptible to reactions, has an immune system that is sensitive to different allergens. Allergic Rhinitis (AR) is a specific allergic reaction with inflammation of the nasal mucosa as the primary symptom. It can be seasonal, perennial, or occupational and accompanied by other complications. 


The diagnosis of AR have changed little over time, but with drastic shifts in lifestyle amidst urbanization, new triggers have surfaced. According to a NHAPS study, 87% of an American resident’s time is spent in enclosed spaces, exposing them to a new profile of indoor allergens. Mold promotes inflammation in the respiratory airways, as the body reacts to toxic compounds produced by fungi. Extended time indoors also leads to excessive secondhand smoke exposure in higher density housing. Tobacco smoke inflames the lung microenvironment and upregulates mucus production. There is diminished mucociliary clearance, which is the innate defense mechanism of the respiratory pathways. This additionally affects the lung microbiota, which is colonized by bacteria, viruses and fungi. Furthermore, the inflammation in different sites of the respiratory tract, as a result of any irritation, is similar for rhinitis, sinusitis and asthma (concept of “united airway”). Due to such similar response patterns, antigens affecting one area, causing rhinitis, could develop into sinusitis or asthma responses. Indoor allergens thus behave as new triggers of AR, and increase the probability of complications due to the united airway.


The external environment heavily impacts those suffering from AR. Global warming, accelerated in cities, has a unique impact on the severity of AR that people face. New allergens such as exhaust particles, increases primary allergic response and causes more severe, long term respiratory diseases. Allergens such as pollen interact with increased carbon dioxide concentrations, changing their composition and anatomy. Pollen from plants grown in futuristic levels of CO2 (700𝜇mol/mol) are predicted to be 1.6 times more irritating to the immune system as compared to current levels. Further, AR is a precursor of asthma, the duration and severity of AR is directly correlated to the type of asthma. Thus, understanding trends in asthma patients provides insights into the environmental impact on AR. A study in New Zealand, on an adult sample aged 20-44, revealed the impact of rising temperatures: just 1oC was associated with an increase of 1% in asthma prevalence. Increased temperatures lead to greater production of ozone, which irritates the lungs and increases the risk of an asthma attack. Thus, in addition to the large array of problems caused by global warming, it also immensely affects atopic individuals.


While this shift in environmental conditions is universal, allergens affect certain individuals in particular due to their genetics, subject to variation and modification. Changes to the DNA of a gene lead to alterations in the final protein product of that gene. Such mutations can lead to changes in the phenotype, or observable characteristics of the body. TSLP, a gene associated with allergic rhinitis, shows a single nucleotide polymorphism mutation: a change in a single “letter” of DNA. This gene shows this mutation only in patients suffering from AR. Similarly, certain altered forms of the Charcot-Leyden crystal (CLC), a protein, are only found in AR patients. The effect of genetic variation on the occurrence and severity of allergy is evident. Understanding the cause of these variations delves into the epigenetics of allergies.


The field of epigenetics studies how human behavior and environment affects gene expression. Such changes in the genes of immune system cells result in a higher susceptibility to AR. One example is DNA methylation, an epigenetic mark where a methyl group attaches to a structural part of the DNA, with the help of an enzyme methyltransferase. This process causes genes to be silenced or overexpressed, meaning that either less protein product is generated, or there is excess activation of the gene, further causing changes in the body phenotype. Recent studies on New York pediatric populations bring to light the severity and impact of epigenetics. Children with higher carbon black exposure saw notable changes in their mucosa genes: lower DNA methylation in the mucosal membrane genes caused excessive production of mucus. Similarly, pollen grains affect the CD4+ type of helper T cells in the immune system, which stimulate other parts of the immune system to create a response. This through regulated methylation not only causes AR, but also results in hives. Environmental triggers of AR thus affect the phenotype or observable characteristic of a person, due to the changes at a molecular level.


Today, as the world faces rapid urbanization and global warming, the effects of these factors on atopic individuals becomes a greater concern. Seemingly safe indoor living lifestyles have in turn led to increased AR triggers. From smokeleaden atmospheres to heat-wave plagued cities,  larger numbers of pollutants and higher temperatures have hindered those with AR. The new climate that humans inhabit today affects us in extensive ways, from microscopic changes in DNA to visible symptoms in the respiratory tract. It is up to scientists and global leaders to formulate new solutions and work towards combating this climate change around us, so that perhaps the climate within us becomes healthier!