Allergy, Eczema, Digestion, Asthma, Skin Conditions, General, Infant and Children | May 17, 2016 | Author: The Super Pharmacist
Over the past three decades, there has been a dramatic increase in allergy-linked diseases such as asthma, atopic dermatitis and hay fever in developed (westernised) countries. Even factors such as improved diagnosis and hereditary influence fail to account for the marked rise in incidence of allergic disorders.
In contrast, the low baseline prevalence of allergic disease has not changed significantly over the same period in developing countries. The rapid pace of this epidemiologic shift tends to discount genetic causes, thus directing investigative efforts toward environmental factors instead. Interestingly, a similar trend has been observed for the incidence of autoimmune diseases as well.
While the incidence of many infectious diseases has declined in developed countries as a result of antibiotics, vaccines, improved hygiene and better socioeconomic conditions, there has been an almost parallel upward trend in the incidence of autoimmune diseases.
The ‘hygiene principle’ or more accurately, the ‘hygiene hypothesis,’ put forward to explain this phenomenon, has gained more acceptance in the scientific community.
The ‘hygiene hypothesis’ was first formulated in 1989 by epidemiologist, David Strachan who reported a relationship between family size and development of allergic disorders, and proposed that - a lack of early childhood exposure to infectious agents, symbiotic microorganisms and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system.
It was believed that children must be kept in an environment that is as clean as possible, the hypothesis put forward suggests that being exposed to 'unclean' conditions is good for a child's immune system.
Research has indicated that those children who are kept in very clean environments have a higher rate of allergy type diseases.
According to the ‘hygiene hypothesis,’ the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both allergic and autoimmune diseases.
Australia and New Zealand have among the highest prevalence of allergic disorders in the developed world.
According to a 2013 report issued by the Australasian Society of Clinical Immunology and Allergy (ASCIA), almost 20% of Australians have at least one allergic disease and this prevalence is increasing.
Hospital admissions for anaphylaxis (severe life threatening allergic reaction) have increased 4 fold in the last 20 years. Food-induced anaphylaxis has doubled in the last 10 years and 10% of infants now have an immediate food allergy.
It is predicted that from 2007 to 2050 the number of patients affected by allergic diseases in Australia will increase from 4.1 million (19.6% of the population) to 7.7 million (26.1% of the population).
Recent decades have seen increases in the prevalence of allergic rhinitis, asthma and atopic eczema (although the proportion of people with asthma has plateaued in the past few years).
Evidence that food allergy is becoming more common, however, is limited to changes in prevalence of peanut allergy. Two separate studies of young children showed a doubling of clinical reactivity over 5 years.
In a 2013 study, information on the global patterns and prevalence of food allergy was obtained by surveying all the member countries of the World Allergy Organisation, and some of their neighbouring nations. Australia ranked highest of the 16 countries where this data was available.
Autoimmune diseases affect 5% of Australians and are more common than cancer or heart disease. Immune diseases are among the fastest growing chronic conditions in Australia.
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Over the last several decades, there has been a marked increase in the prevalence of autoimmune diseases such as type 1 diabetes, multiple sclerosis, inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, and celiac disease.
Immune-mediated conditions are thought to result from a complex interplay between genetic predisposition, immune deregulation, and environmental factors. Since genetic basis has not undergone any major changes in such a short period of time, environmental factors are highly suspected to be responsible for this recent outbreak in both allergic and autoimmune disorders.
Increased attention is now being focused on critical environmental factors in the search for the origins of these diseases. Studies of immigrants, epigenetic studies and mapping of the gut microbiota have provided compelling evidence that the environment can fundamentally modulate immune function in humans. Poorly developed or broken immune tolerance plays a role in the pathogenesis of many diseases such as allergy, autoimmunity, and even cancer.
The human body contains tenfold more microbial cells than human cells. These microorganisms colonise practically every surface of the human body that is exposed to the external environment, including the skin, oral cavity, respiratory, urogenital and gastrointestinal tract. Of these body sites, the gastrointestinal tract is by far the most densely colonised organ.
The complex community of microorganisms residing in or passing through the gastrointestinal tract is referred to as the intestinal microbiota.
Our gut flora comprises a critical component of our immune system. When there is a lack of beneficial bacteria or overgrowth of harmful bacteria, yeast, or parasites this leads to a condition called leaky gut syndrome. This is simply loss of the normal barrier function of the intestine leading to increased intestinal permeability. As with food sensitivities, the resulting increased intestinal permeability may contribute to the pathogenesis of various autoimmune diseases. Therefore, the integrity of the intestinal barrier is a critically important factor in autoimmune disease.
The microbiota is variable and shows temporal fluctuation in early life. When a steady state is reached, the composition of the gut flora remains relatively stable over time, providing that no major changes in lifestyle or environment occur. Early environmental exposures are thus considered the key determinant of adult gut microbiota, as is the type of diet consumed.
The geographical distribution of allergic and autoimmune diseases is a mirror image of the geographical distribution of various infectious diseases, including hepatitis A virus, gastrointestinal infections and parasitic infections. Further clues about the influence of environmental factors on the development of the gut microbiota have been obtained from studies of infants in Estonia and Sweden.
These provide some of the first evidence that the composition of gut microflora between non-western and western children in early life differs and that these disparities could be associated with the manifestation of allergic diseases in later life.
Using novel molecular-based methods, a Swedish study revealed that a more diverse gut microbiota early in life is associated with protection against allergy at the age of 5 years.
The immunomodulatory changes appear to occur within 10 years after arrival, and these changes are not restricted to young people only but also occur in adults as well. This immunomodulation by “cultural adaptation”, which leads to changes in disease susceptibility, appears to be universal and has been reported for various inflammatory diseases, including asthma and allergic diseases, autoimmune diseases, such as type 1 diabetes and multiple sclerosis,obesity and type 2 diabetes, depression and civilization cancers.
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Previous studies reveal that microbe-rich environments confer protection against allergic and autoimmune diseases, but it is likely that declining biodiversity is more generally responsible for human immune dysfunction.
According to a recent study, atopic individuals had lower environmental biodiversity compared with healthy adolescents in the surroundings of their homes. The atopic adolescents also had significantly lower diversity of Gram-negative gamma proteobacteria on their skin.
The health effects of natural environments are obvious, but difficult to examine experimentally. According to one study, farm exposure during pregnancy increases the number and function of cord blood regulatory T cells (Treg cells).
Two of the multiple functions of Treg cells are:
There is mounting evidence for the hypothesis that low early life microbial exposure is associated with persisting methylation (silencing) of a specific gene in maternal regulatory T cells that ordinarily exerts a critical protective effect against allergic disease in maternal offspring.
Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. This protective effect is achieved via epigenetic regulation. Urbanization and general loss of biodiversity, combined with sedentary indoor lifestyles have been a principle driving factor leading to microbial deprivation.
Mounting evidence shows that alterations in the indigenous microbiota correlate with inflammatory disease states. Dysbiosis refers to a reduced diversity and disturbed composition of the gut microbial community. Not only does it influence the occurrence of asthma and allergies, but it also influences the development of other chronic and relapsing inflammatory conditions that include type 1 diabetes, inflammatory bowel disease, obesity and even psychiatric disorders, such as depression.
Moreover, an imbalance of ‘pro-inflammatory’ and ‘anti-inflammatory’ microbes may also result in an increased susceptibility of the host to inflammatory diseases and could explain the increase in paediatric inflammatory bowel disease, one of the many inflammatory diseases being reported with increasing frequency in westernized countries.
Antibiotics modulate microbiota, and the effect may be long-term. One-week course affected the gut microbiota even for three years.
To date, the findings from epidemiologic studies have supported and refuted an association between antibiotic use in early life and the development of asthma.
A recent meta-analysis of antibiotic use in the first year of life has reported a twofold increased risk of childhood asthma following antibiotic use, but no association among studies conducted prospectively.
A longitudinal study (known as the Study of Asthma, Genes and the Environment) of a cohort of 13,980 children born in Manitoba in 1995 and continuously registered with the Manitoba Health Services Insurance Plan (MHSIP) until 2003.
The likelihood of asthma at age 7 years according to antibiotic prescription use during the first year of life was determined. Following adjustment for gender, maternal history of asthma, number of siblings, urban/rural location, and the number of health-care visits, antibiotic use in the first year of life (vs no use) was significantly associated with greater odds of the development of asthma at age 7. This likelihood increased with the number of antibiotic courses. In a model that adjusted for all risk factors for asthma, asthma was significantly more likely to develop in children receiving antibiotics in a dose-dependent manner.
Indoor and outdoor pollution is a major environmental risk factor for asthma and allergy not only increasing the prevalence of long-term symptoms but also acute attacks.The association studies indicate that ambient air pollution is connected to asthma, rhinitis, rhino-conjunctivitis, and acute respiratory infections.
Climate change has direct impacts on aeroallergens, in particular pollens and mold spores and allergic diseases. Pre-Industrial CO2 levels in 1870 were 280 ppm, followed by a steady increase of 35% by 2005 to 379 ppm, with urban areas exhibiting the highest levels. Several studies have demonstrated direct correlations between rising CO2 and increases in both pollen and biomass levels, as well as increased allergenicity of the pollen.
Epigenetics is the study, in the field of genetics, of how environmental factors can change how genes are expressed. For example, one epigenetic mechanism is the addition of a methyl group to the DNA of cells. This called ‘methylation.’ Another epigenetic mechanism is the removal or ‘demethylation' of DNA within cells. Epigenetics alters gene expression rather than altering the genetic code itself.
Cancer: While epigenetic changes are required for normal development and health, they can also be responsible for some disease states.
The first human disease to be linked to epigenetics was cancer, in 1983. Researchers found that diseased tissue from patients with colorectal cancer had less DNA methylation than normal tissue from the same patients.
There are no clearly established guidelines for primary prevention of allergic disease or any established methods to non-specifically strengthen tolerance in established disease. However, data have accumulated to indicate that some simple behavioural activities can confer some protection against or alleviate allergic diseases, providing indirect evidence of their beneficial effects on tolerance. Not unexpectedly, such interventions include physical exercise, a healthy diet and connection with the natural world and countryside.
There is much evidence emphasizing the risks to health of a sedentary lifestyle. A lack of physical exercise increases the inflammatory burden, independently of obesity, and decrease systemic low level inflammation. The anti-inflammatory effects of physical exercise seem to be mediated by activating the regulatory circuits, including regulatory T cells. For example, in healthy adults, a 12-week program of moderate exercise 3 times per week significantly improved regulatory T cell numbers and function. Moderate exercise for 12 weeks in patients with type 2 diabetes, significantly decreased HbA1c levels. The anti-inflammatory effect of exercise has also been demonstrated in a murine model of asthma.
In addition to micro-organisms, dietary factors have been extensively studied to uncover possible additional factors behind the asthma and allergy epidemics in modern urban environments, given the modulatory potential of nutrients on epigenetics, intestinal microbiota and immune function. While an inverse link between various nutrients or vitamins and occurrence of allergic diseases has been proposed in cross-sectional studies, the results are inconsistent and inconclusive.
However, a systematic review based on 62 reports and 11 databases concludes that although the epidemiologic evidence thus far is weak, it supports a beneficial role for increased consumption of more fruits and vegetables, associated with better asthma and allergy outcomes.
For example, a traditional Mediterranean diet confers protection against persistent wheeze and atopy.
It must be also born in mind that at least a part of the beneficial effect of fresh fruit and vegetables may be mediated by microorganisms abundantly present on their surfaces.
Vitamin D deficiency has been suspected to play a role in the ´asthma epidemic´ as it may influence genomic programming of foetal development and subsequent disease risk and is tightly linked to diet and exposure to sunlight. This hypothesis is in the process of being tested in a large controlled trial in pregnant women and their offspring for the primary prevention of asthma.
The benefits of probiotics to prevent or treat allergic diseases and asthma remain inconclusive. Bacteria-based products hold great promise for allergy prevention, but in the case of probiotics, the most beneficial bacterial strains, doses, duration and timing of supplementation are not determined.
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