Already more than 100 years two subjects - asthma and allergy - are indissolubly connected. One who speaking about asthma, always recollects an allergy. But till present time the main question is not answered: is allergy a veritable asthma cause or they coexist developing independently from each other?

The international committee of experts GINA 2002, on the one hand, tries to establish allergy and asthma causative relationship and on the another - is compelled to admit the fact, that allergy and asthma are often combined, but are not connected with causative relationship.

Here are some quote some positions of 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 "…to a third of all cases of asthma could be categorized as non allergic" (p. 51).

As a result experts come to the following conclusion: "However, 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).

Therefore it is possible to make two conclusions from the facts resulted in this report:

1. Atopy (allergy) is quite often combined with a bronchial asthma, but in 30-50 % of all the cases does not cause this disease.

2. In spite of the similar immunologic mechanisms presented in atopy and asthma, atopy cannot be considered as a veritable asthma cause.

What are these mechanisms? As it is known, they are connected with two different subpopulations of lymphocytes helpers: Тh1- and Тh2 types. The first type cells are responsible for the normal immune response protecting human organism from all the infections. A prevalence of the second - Тh2- helper subtype activity - leads to IgE depending immune path resulting the synthesis of antibodies to the different "allergens". And immunity starts to perceive as "allergens" a coat of dogs and cats, pollen of trees, grass and flowers, different food, medicines and etc.

Th2-helpers participating actively in bronchial asthma pathogenesis produce a number of cytokines such as IL-4, IL-5, IL-9, IL-13 и IL-16. Th2-cytokines are responsible for classic hypersensitivity delayed-type (or cell-mediated hypersensitivity) reaction. And produced by Th2-lymphocytes cytokine IL-5 causes eosinophilous inflammation irrespective of asthma character - connected with atopy or not.

With this in mind one can propose that the factor leading to the inflammatory process and changing immune response from Th1 - to Th2 - helper path may be a veritable asthma cause. And if such factor exists, the inflammation caused by him, on the one hand, leads to asthma, and on the another - to atopy, aggravating asthma or existing without clinical symptoms, as a marker of immunity system changes.

What it is the factor? It is absolutely clear, that it should be closely connected with immune system. But as it is known from its evolution the human immune system has developed first of all as protection against infection. Therefore it is absolutely logical to assume, that the factor causing inflammation in the respiratory tract and changing immune response from the Th1- to Тh2- helper type leading to asthma development should be of infectious nature. Besides it is necessary to recollect not so long ago existed in classification and till now remained in memories of physicians the infectious form of bronchial asthma. And one can direct to the data that the most severe asthma cases are accompanied with neutrophilous - infectious - inflammation. Naturally one can ask a question: which is this infection and how it is connected with asthma and atopy?

The kind of this microorganism was defined by the means of the bacteriological researches of sputum and intestinal content. Sputum bacteriological analysis has 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 all the patients, other fungi - Aspergillus and Penicillium was found in 2.3% and 4.1% correspondently. All these fungal microorganisms were associated with bacteria: streptococci and staphylococci were found in 55.9% and 52.4% correspondently. Other bacterial microorganisms - Klebsiella pneum. and E. Coli were found in 12.8% and 2.4% correspondently. Very seldom one could find other bacteria, in particular Pseudomonas spp. Thus Pseudomonas aeruginosa was found only in 0.087% in all the patients' sputum. Thus the most often sputum bacteriological analysis were presented by fungal microorganisms. These microorganisms were found practically in majority of the patients under investigation. In all the cases Candida was associated with different types of bacteria. And only in one case it has been revealed exclusively Candida albicans. At the same time Candida was found in 99.6% of intestinal content of asthmatics under study. Thus the obtained data correspond to the last years' investigations, devoted to the increasing (over 80% of cases) of bacteriological sputum analysis in asthmatics associated with fungal infection presented by Candida albicans.

It is necessary to note that Candida. spp fungi are able usually to inhabit the healthy people. In particular Candida albicans is a usual saprophyte which can be found on the human's skin, oral cavity and mucosa. On healthy people skin it is found in 19-70%, in oral cavity of adults - in 20-30% and newborns - in 90% (!) of the whole population. And the intestinal tract of the adults and children contains these fungi in 36% and 50% accordingly. Thus according to our own and literature data in bronchial asthma people Candida spp. find out in the most of cases from sputum and intestinal content.

Analyzing these data, we found a direct correlation between Candida spp. prevalence in peoples with asthma rate increasing for the last 50 years. In 50th years in Russia the number of Candida carriers was 5-15% and the asthma frequency was 0.1-0.5% in the whole population correspondently.

In 60-80th years these indices increased: the number of Candida carriers was 20-53% and the asthma frequency reached 1-3% of the whole population.

Per 1990-2001 years the percent of Candida carriers and asthmatics reached on average 60-70% and 4-15% of the whole population correspondently. Thus, both of these indices have simultaneously grown for these years not less than in 5-10 times.

Settled down on the human mucosa Candida microorganisms in non-favorable situations (massive antibiotic therapy, weakness of local immune protection and etc.) start to active colonization and production of different toxins which cause epithelium damage. Some of Candida toxins are able to liberate histamine from must cells leading to mucosa initial inflammation. Such pathologic way can activate an inflammatory process by Candida in the bronchial tree. And further immune system reactions with all the following consequences are started in organism.

Thus, the beginning of Candida reproduction and its toxins excretion may cause the initial inflammatory process which can have at the beginning neutrophilous character. It occurs also because the pathologic action of other microbes strongly increases in Candida presence, and they take active participation in the development and progressing of inflammatory process the respiratory tract mucosa. And the further changing of Th1-helper to Тh2-helper immune answer leads to eosinophilous inflammation with the following asthma development. And the existing data from the scientific literature confirm, that Candida fungal infection is capable to "switch" immune system from the normal - Th1-helper to the pathological Th2-helper response.

So one can consider asthma inflammation as human immune cellular mechanisms attempt "crash" release from massive fungal Candida colonization because it is possible to cause severe issues' damage due to phagocytosis. And as a result it 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 allergic (antibody-mediators) reactions of immediate type on different allergens in organism, being shown by paroxysmal bronchial spasm on a background of inflammatory process persisting in a bronchial tree. Inflammatory reactions of the cellular-mediated type with participation of Т-lymphocites-killers simultaneously proceed in bronchial tree. As it is known, they develop in cases when the immune system meets with antigens on a surface of alien cells.

Thus, it is possible to believe, that a veritable cause of bronchial asthma development can be Candida yeast fungi. These microorganisms are considered to be saprophytes living in mouth and human intestinal tract. And fungi uncontrollable reproduction and colonization on intestinal tract mucosa induces the change of immune response from Тh1- to Тh2-helper way that leads to atopy. And its penetration to the respiratory tract in associations with bacteria may induce initial neutrophilous inflammation. And the following change from Тh1- to Тh2-helper immune response transforms inflammatory process to eosinophilous type, that leads to of actually bronchial asthma formation. And consequently there can exist atopy without asthma, such as asthma without atopy. In case of their combination atopy is one of the factors additionally aggravating inflammatory process in a bronchial tree and promoting its chronic character.

The asthma and allergy rates growing are aggravated by frequent antibiotics treatment of patients. And if once again to recollect data frequency of Candida carrier in people and asthma rate in different years it is possible to notice, that their growth is observed with the beginning of active wide spectrum action antibiotics use in medicine at the end of 50th - the beginning of 60th years. This question understands in details in the famous monograph "Candida mycosis as a complication of antibacterial treatment" written by A. Arievich and Z. Stepanishcheva just in these years.

The present day Candida carriers' level in people (from 20 up to 70 %) can not be considered as normal. Not casually last decade frequency of cases of a local and system candidiasis has grown up to such degree, that wide spectrum of action antifungal preparations are advertised in mass media. And if to consider all resulted above a reason becomes clear why the international experts committee GINA 2002 has come to a following conclusion: «Despite of 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». Thus, all three factors: the wide beginning of antibiotics treatment, growth of Candida carrier level and a bronchial asthma rate growing are observed at the same period.

The infectious nature of asthma explains also other fact: the more frequent sick rate among relatives because the household way of transfer of a fungal infection is well-known. One can observe the cases of successively developing asthma at closely contacting among themselves not blood relatives, for example in husband and his wife. It is inexplicable from positions of heredity, and it is clear from the position of fungal infection. And the last: simultaneous disease cases among brothers and sisters are more often at twins. It explains that probability of simultaneous infection with Candida from mother to twins is more often. That is why there were, in essence, unsuccessful attempts to connect asthma with hereditability. Discrepancy of data on this question also explains by infectious, instead of hereditary causality of bronchial asthma! Therefore even among twins one can find the cases when both are asthmatics and when one of twins is sick and another is absolutely healthy.

One can ask a general question: should be every person infected by Candida microorganisms? Earlier, in 1950th years carefully provided clinical and epidemiological researches had been shown, that yeast fungi Candida should be found out in healthy people from mouth and pharynx no more than in 5%. And undoubtedly non-controlled growth of these pathogenic microorganisms has led to worseness of public health. Apparently, microorganisms in general as a cause of many nonspecific inflammatory diseases, but not just asthma, play more important role than it is now considered. And it first of all concerns the cases when bacteria and fungi act on human organs and systems not by "frontal" attack as, for example, in purulent diseases, but more refined - by switching of immune system response from a normal to a pathological way.

Apparently, has come a time of revision in mutual relations of person and a microbe as the common system in which both "partners" should support correct game rules. And such revision finally can lead to essential change of our general representations about causality in medicine.

The "Medical Newspaper", (Moscow), N 54, 21. 07. 2006

Dr. med Victor N. Solopov,
"Asthma Service" Chief Adviser
www.solopov.ru/eng/main.htm