Bronchial Asthma - Is The Allergic Theory Not Correct? Candida Role

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Bronchial Asthma - Is The Allergic Theory Not Correct? Candida Role

In The Disease Development

Medical News Today - UK

Main Category: Respiratory / Asthma News

http://www.medicalnewstoday.com/medicalnews.php?newsid=69238

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: Òh1- and Òh2

types. The first type cells are responsible for the normal immune

response protecting human organism from all the infections. A

prevalence of the second - Òh2- 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 è 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 Òh2- 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 Òh2-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 Ò-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 Òh1- to Òh2-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 Òh1- to Òh2-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