Dr. Victor N.
Solopov
Medical center "Asthma Service"
Bronchial
Asthma - Is The Allergic Theory Wrong?
Candida's Role In The Disease Development
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: ̉h1- and ̉h2 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 (̉h2- 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 ̉h2-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 ̉-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 ̉h1- to ̉h2-helper,
and that leads to atopy. Its penetration to the respiratory tract
with associated bacteria may induce initial neutrophilous
inflammation. The consequential change from ̉h1- to ̉h2-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.
translated from: "The Medical Newspaper" (Moscow), 21.07.2006
Dr. Victor N. Solopov
solopov@asthma.ru
