For over one hundred years, asthma and allergy have been inextricably linked. Whenever asthma is discussed, allergy is invariably mentioned, but until recently the key question remained unanswered: Does allergy cause asthma, or do they coexist, developing independently of each other?
The international committee of experts at GINA 2002, tried to establish a causal relationship between allergy and asthma, but were forced to admit defeat. Here are some quotes from the GINA 2002 report:
1. "However, when expressed in the lower airways, atopy is one of the strongest risk factors for asthma." (p. 4). At the same time one can find: "Atopy occurs in 30 to 50 percent of the population in developed countries and frequently occurs in the absence of disease" (p. 4).
2. "Asthma… is frequently found in association with atopy, which is defined as the production of abnormal amounts of immunoglobulin E (IgE) directed to episodes expressed on common environmental allergens…" (p. 4). At the same time"…most studies report an inconsistent association between the increase of atopy and the increase of asthma" (p. 30).
3. "In many cases, especially in children and young adults, asthma is associated with atopy manifesting through immunoglobulin E (IgE) - dependent mechanisms. At a population level, the contribution of atopy to the asthma phenotype has been estimated to be 40 percent in both children and adults." (p. 50). But "… a third of all cases of asthma could be categorized as non allergic" (p. 51).
The experts concluded that: "A major unresolved question is whether exposure to allergens and occupational sensitizers is indeed the primary cause of the development of new asthma, or if this exposure merely triggers asthma attacks or leads to the persistence of symptoms in subjects who already have asthma" (p. 32). Two conclusions can be formed from the facts presented in this report:
1. Atopy (allergy) is often combined with bronchial asthma, but in 30-50% of all cases, it does not cause the disease.
2. Despite similar immunological mechanisms in atopy and asthma, atopy cannot be the cause of asthma.
What are these mechanisms? They are connected by two different subpopulations of lymphocytes helpers: Th1- and Th2 types. The first type are responsible for the normal immune response which protects the human organism from infection. A prevalence of activity of the second type (Th2- helper subtype) leads to IgE synthesis of antibodies to different "allergens" - the precise allergen depends on which immune pathway is affected. When this happens, the immune system starts to perceive animal hair/fur, pollen, various foodstuffs, medicines, etc. as "allergens".
Th2-helpers active in bronchial asthma pathogenesis produce a number of cytokines such as IL-4, IL-5, IL-9, IL-13 and IL-16. Th2-cytokines are responsible for classic hypersensitivity delayed-type reaction (also known as cell-mediated hypersensitivity); and cytokine IL-5 (produced by Th2-lymphocytes) causes eosinophilous inflammation, irrespective of the presence of asthma or atopy.
From these facts, it can be proposed that the factor that gives rise to the inflammatory process and changes in the immune response from Th1 - to Th2 - helper path, may be the true cause of asthma. If such a factor exists, the inflammation caused by it, on the one hand leads to asthma, and on the other, to atopy (which can aggravate asthma or exist without clinical symptoms) as a marker of immunity system changes.
What could this factor be? Clearly, it must be closely connected with the immune system. As the immune system evolved primarily as a protection against infection, it is logical to assume that the factor is infectious. As many physicians know, until recently bronchial asthma was classified as infectious. In addition, the data shows that the most severe asthma cases are accompanied by neutrophilous - infectious - inflammation. Taken together this evidence leads one to ask: 1) Which infection could it be? and 2) How is it connected with asthma and atopy?
Identification of the micro-organism should be possible from bacteriological analyses of sputum and intestinal content of patients. Analyses have shown the following results:
· Fungal microorganisms are revealed in 69.8 % of all the analyses.
· Candida spp. were found in asthmatics' sputum in 63.3% of patients.
· Other fungi - Aspergillus and Penicillium - were found in 2.3% and 4.1% of samples, respectively.
· All these fungal micro-organisms were associated with bacteria: Streptococci and staphylococci were found in 55.9% and 52.4% respectively.
· Other bacterial micro-organisms - Klebsiella pneum. and E. Coli - were found in 12.8% and 2.4% respectively.
· Occasionally other bacteria were found. In particular Pseudomonas spp, e.g. Pseudomonas aeruginosa were found in 0.087% of all patients' sputum.
· Fungal micro-organisms were the most prevalent in sputum bacteriological analyses, and were found in the majority of the patients under investigation. In almost all cases, Candida was accompanied by various types of bacteria. Only in one case, was Candida albicans found without any co-existing bacteria.
· At the same time, Candida was found in 99.6% of the intestinal content of the asthmatics under study.
It should be noted that Candida. spp are often found in healthy people. In particular Candida albicans is a saprophyte commonly found on human skin, the oral cavity and mucosa. Its prevalence in the general population is as follows: on the skin (19-70%); in the oral cavity of adults (20-30%); in newborns' oral cavities (90%); in the intestinal tract of adults (36%), and in the intestinal tract of children (50%). Thus, according to the literature and our own data, most people with bronchial asthma have Candida spp. in their sputum and intestines.
When analyzing this data, we found a direct correlation between the increase in Candida spp. and the rise in asthma over the last 50 years. Fifty years ago, the number of Candida carriers in Russia was 5-15% of the population, and the asthma frequency was 0.1-0.5%.
In the 1960-1980s these indices increased so that the percentage of Candida carriers became 20-53% and asthma frequency reached 1-3% of the whole population.
During 1990-2001 the percentage of Candida carriers and asthmatics reached on average 60-70% and 4-15% of the whole population, respectively. Thus, both of these indices have grown concurrently over these years, not less than 5-10 times.
When Candida micro-organisms settle on the human mucosa in unhealthy situations (caused by massive antibiotic therapy, local immune system weakness etc.) they start active colonization, and produce toxins that cause epithelium damage. Some Candida toxins can liberate histamine from mast cells leading to initial mucosal inflammation, and further immune system reactions.
Candida reproduction and excretion of its toxins can cause an initial inflammatory process, which can be neutrophilous In addition, the presence of Candida increases the pathological action of other microbes, which exacerbates the inflammatory process in the respiratory tract mucosa. The further mutation of Th1-helper to Th2-helper leads directly to eosinophilous inflammation and the development of asthma. Data from the scientific literature confirms that Candida fungal infection is capable of "switching" the immune system from normal (Th1-helper) to the pathological Th2-helper response.
Asthma inflammation may be an attempt by human immune cellular mechanisms to "crash" release from massive fungal Candida colonization, in order to avoid severe damage from phagocytosis. As a result its immunity is compelled to pass on the less damaging - antibody productive way - with participation of Th2-helper lymphocytes, which leads to atopy. Generated atopy causes acute allergic (antibody-mediators) reactions to different allergens in the organism, shown by paroxysmal bronchial spasm against a background of an inflammatory process persisting in the bronchial tree. Inflammatory reactions of the cellular-mediated type with participation of T-lymphocites-killers simultaneously proceed in the bronchial tree. As is known, they develop in those cases where the immune system meets antigens on the surface of alien cells.
In summary, it is possible that the true cause of bronchial asthma development could be Candida yeast-fungi. These microorganisms are considered to be saprophytes living in the mouth and human intestinal tract. Their uncontrollable reproduction and colonization on the intestinal tract mucosa induces a change in immune response from Th1- to Th2-helper, and that leads to atopy. Its penetration to the respiratory tract with associated bacteria may induce initial neutrophilous inflammation. The consequential change from Th1- to Th2-helper immune response transforms the inflammatory process to an eosinophilous type, that leads to bronchial asthma Consequently, atopy can exist without asthma, and asthma without atopy. When they do combine, atopy can exacerbate the inflammatory process in the bronchial tree, helping to turn it into a chronic condition
The asthma and allergy growth rates may be induced by frequent antibiotic treatment of patients. Looking again at the frequency data of Candida and asthma in different years, it is noticeable that their growth coincides with the beginning of medicinal usage of wide-spectrum antibiotics at the end of the 1950s and beginning of 1960s. This observation supports the famous monograph "Candida mycosis as a complication of antibacterial treatment" written by A. Arievich and Z. Stepanishcheva.
The present day level of incidence of Candida in healthy people (70%) cannot be considered to be normal. Local and systemic candidiasis have spread to such a degree, that wide-spectrum antifungal preparations are advertised in the mass media. When considering all of these facts together, it becomes clear why the international experts committee GINA 2002 came to following conclusion: "Despite efforts on improvement of rendering assistance in patients with BA undertaken within last decade, the majority of patients has not received advantage of achievements in this field". It is no coincidence that all three factors: the wide beginning of antibiotics treatment, growth of Candida carrier level and a bronchial asthma rate growing, are observed over the same period.
The infectious nature of asthma explains another fact. It is well known that fungal infections can be transferred within households. It has also been observed that asthma is passed among contacts who are not blood relatives, for example between husband and wife. This is inexplicable in terms of heredity, but explained by a fungal infection. It also explains why twins suffer more than brothers and sisters - the probability of simultaneous infection with Candida from mother to twins is higher. This explains the unsuccessful attempts to connect asthma with heredity, and it even explains why one can observe cases of asthmatic twins where one is sick and the other is absolutely healthy.
One can ask a general question: should every person be infected with Candida microorganisms? Clinical and epidemiological research done in 1950 show that yeast fungi Candida were found in the mouth and pharynx of healthy people, in less than 5% of the population. Undoubtedly the uncontrolled growth of these pathogenic microorganisms has had a detrimental effect on public health. It appears that microorganisms in general are implicated as a cause of many non-specific inflammatory diseases, not just asthma, and play a more important role than is currently considered. This particularly applies to those cases where bacteria and fungi act on human organs and systems not by "frontal" attack as, for example, in purulent diseases, but in a more refined way - by switching the immune system response from normal to pathological.
We need to revise our view of how people and microbes live together symbiotically, with both "partners" following the rules of the game. That revision could lead to a change in our general model of causality in medicine.
Dr. Victor. N. Solopov
Translated from: The "Medical Newspaper", (Moscow), N 54, 21. 07. 2006