Pool chlorine hypothesis
Encyclopedia
The pool chlorine hypothesis is the hypothesis
that long-term attendance at indoor chlorinated
swimming pools by children up to the age of about 6-7 years is a major factor in the rise of asthma
in rich countries since the late twentieth century. A narrower version of the hypothesis, i.e. that asthma may be induced by chlorine related compounds from swimming pools, has been stated based on a small numbers of cases at least as early as 1995.. An empirically motivated statement of the wider form of the hypothesis is first known to have been published on the basis of tests of the effects of nitrogen trichloride
above chlorinated water on the lung
as well as epidemiological
evidence by a group of medical researchers led by Alfred Bernard of the Department of Public Health in the Catholic University of Louvain in Brussels
, Belgium
in 2003. In the epidemiological studies, the association between chlorinated swimming pools and asthma was found to be more significant than factors such as age, sex, ethnic origin, socioeconomic status, exposure to domestic animals and passive smoking
(in a study in Brussels
), and independent of altitude
, climate
, and GDP per capita (in a Europe
-wide study of 21 countries).
has been directly linked as a factor causing asthma in two lifeguard
s and a swimming teacher. A study of 624 swimming pool workers found a significant correlation between upper respiratory symptoms and their total exposure to nitrogen trichloride. The study also found an excess risk in the workers for the specific symptoms indicative of asthma. In a study by Alfred Bernard's group, two hours exposure to an average concentration of 0.490 mg/m3 of nitrogen trichloride above a swimming pool was found in both children and adults to significantly increase the levels of the alveolar surfactant associated proteins A and B, which indicate hyperpermeability of lung epithelium. In other words, exposure to nitrogen trichloride was found to weaken the protective nature of the surface of the lungs.
inflammation
(measured by exhaled nitric oxide
) independently of other factors, while for those children susceptible to allergic problems, as defined by having a blood serum
level of immunoglobulin E
greater than 100 kIU
/L
, their total time spent at indoor chlorinated swimming pools was a strong predictor of the probability that they would have asthma
..
and the Ardenne region in 2003, asthma and exercise-induced bronchoconstriction (a test related to potential breathing difficulties) were not found to have any statistically significant
correlation with the demographic and environmental factors of age, sex, ethnic origin, socioeconomic status or exposure to pet
s or passive smoking
alone. However, when the time spent at chlorinated swimming pools (modified for pool height as a statistical way to indicate likely concentrations of chlorine related gases) was adjusted for exposure to pets and passive smoking, the significance of the correlations with asthma increased further. The authors describe this saying that a "very strong argument in [favour] of causality [between pool attendance and asthma] comes from the synergistic action of exposure to pets and [passive smoking], two well documented risk factors for asthma, which together considerably increase the strength of the associations, to levels largely above those usually observed in asthma epidemiology."
In a later study by the Bernard group of 190,000 children in 21 countries in Europe
, it was found that 13 to 14 year old children were 2% to 3.5% more likely to have or have had asthma for every additional indoor chlorinated pool per 100,000 inhabitants in their place of residence. Other atopic
diseases such as hay fever
or atopic dermatitis
were found to be not associated with the presence of the pools. The association of asthma with the number of indoor chlorinated swimming pools per 100,000 inhabitants was found by the authors to be independent of altitude
, climate
, and GDP per capita.
Following publication of Bernard's group's 2006 study, some concerns by P.A. Eggleston and a response by Bernard's group were published. For example, Eggleston argued that if "chlorinated compounds at indoor swimming pools could cause asthma", then "frequent and longer exposures at home" should be even stronger causes of asthma, in contradiction to the available evidence from a single group of children. Bernard's group's response was that while children at an indoor chlorinated pool "actively inhale [the chlorination products] as gases, aerosols, or even water", they are not usually involved in household cleaning tasks, so they could benefit from the hygienic effects of the chlorine based cleaning products while avoiding any significant contact with the related gases. Members of Bernard's group's declared that they had no potentially conflicting financial interests, while Eggleston declared that he had received money from the United States based group called the Chlorine Chemistry Council. In a "Faculty Disclosure" statement in an asthma-related publication, it was declared that Eggleston is "a consultant for Chlorine Chemistry Council, Church and Dwight
, Merck Sharp & Dohme
, and Procter & Gamble
, and is on the speakers' bureau for AstraZeneca
, GlaxoSmithKline
, and Merck."
could be that frequent, long-term disruption of the epithelium
of the lung
, which normally provides a protective barrier against various pathogen
s, could allow allergen
s to cross this barrier. This process would also cause certain protein
s from the lung epithelium to have increased blood serum
concentrations.
still lacks a close causal link with asthma, and that the hygiene hypothesis might be most relevant for a restricted number of types of infections, such as those due to parasites.
Hypothesis
A hypothesis is a proposed explanation for a phenomenon. The term derives from the Greek, ὑποτιθέναι – hypotithenai meaning "to put under" or "to suppose". For a hypothesis to be put forward as a scientific hypothesis, the scientific method requires that one can test it...
that long-term attendance at indoor chlorinated
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
swimming pools by children up to the age of about 6-7 years is a major factor in the rise of asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
in rich countries since the late twentieth century. A narrower version of the hypothesis, i.e. that asthma may be induced by chlorine related compounds from swimming pools, has been stated based on a small numbers of cases at least as early as 1995.. An empirically motivated statement of the wider form of the hypothesis is first known to have been published on the basis of tests of the effects of nitrogen trichloride
Nitrogen trichloride
Nitrogen trichloride, also known as trichloramine, is the chemical compound with the formula NCl3. This yellow, oily, pungent-smelling liquid is most commonly encountered as a byproduct of chemical reactions between ammonia-derivatives and chlorine .In pure form, NCl3 is highly reactive...
above chlorinated water on the lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
as well as epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
evidence by a group of medical researchers led by Alfred Bernard of the Department of Public Health in the Catholic University of Louvain in Brussels
Brussels
Brussels , officially the Brussels Region or Brussels-Capital Region , is the capital of Belgium and the de facto capital of the European Union...
, Belgium
Belgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
in 2003. In the epidemiological studies, the association between chlorinated swimming pools and asthma was found to be more significant than factors such as age, sex, ethnic origin, socioeconomic status, exposure to domestic animals and passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...
(in a study in Brussels
Brussels
Brussels , officially the Brussels Region or Brussels-Capital Region , is the capital of Belgium and the de facto capital of the European Union...
), and independent of altitude
Altitude
Altitude or height is defined based on the context in which it is used . As a general definition, altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The reference datum also often varies according to the context...
, climate
Climate
Climate encompasses the statistics of temperature, humidity, atmospheric pressure, wind, rainfall, atmospheric particle count and other meteorological elemental measurements in a given region over long periods...
, and GDP per capita (in a Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
-wide study of 21 countries).
Effects of nitrogen trichloride (trichloramine) on the human lung
Nitrogen trichlorideNitrogen trichloride
Nitrogen trichloride, also known as trichloramine, is the chemical compound with the formula NCl3. This yellow, oily, pungent-smelling liquid is most commonly encountered as a byproduct of chemical reactions between ammonia-derivatives and chlorine .In pure form, NCl3 is highly reactive...
has been directly linked as a factor causing asthma in two lifeguard
Lifeguard
A lifeguard supervises the safety and rescue of swimmers, surfers, and other water sports participants such as in a swimming pool, water park, or beach. Lifeguards are strong swimmers and trained in first aid, certified in water rescue using a variety of aids and equipment depending on...
s and a swimming teacher. A study of 624 swimming pool workers found a significant correlation between upper respiratory symptoms and their total exposure to nitrogen trichloride. The study also found an excess risk in the workers for the specific symptoms indicative of asthma. In a study by Alfred Bernard's group, two hours exposure to an average concentration of 0.490 mg/m3 of nitrogen trichloride above a swimming pool was found in both children and adults to significantly increase the levels of the alveolar surfactant associated proteins A and B, which indicate hyperpermeability of lung epithelium. In other words, exposure to nitrogen trichloride was found to weaken the protective nature of the surface of the lungs.
Epidemiological studies
In a study of 341 schoolchildren, Bernard and his colleagues found that long-term attendance at indoor chlorinated swimming pools by the children up to the age of about 6-7 years was a strong predictor of airwayAirway
The pulmonary airway comprises those parts of the respiratory system through which air flows, conceptually beginning at the nose and mouth, and terminating in the alveoli...
inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
(measured by exhaled nitric oxide
Exhaled nitric oxide
In medicine, exhaled nitric oxide can be measured in a breath test for asthma or other conditions characterized by airway inflammation. Nitric oxide is a gaseous molecule produced by certain cell types in an inflammatory response. The fraction of exhaled NO is a promising biomarker for the...
) independently of other factors, while for those children susceptible to allergic problems, as defined by having a blood serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
level of immunoglobulin E
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
greater than 100 kIU
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...
/L
Litre
pic|200px|right|thumb|One litre is equivalent to this cubeEach side is 10 cm1 litre water = 1 kilogram water The litre is a metric system unit of volume equal to 1 cubic decimetre , to 1,000 cubic centimetres , and to 1/1,000 cubic metre...
, their total time spent at indoor chlorinated swimming pools was a strong predictor of the probability that they would have asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
..
Relations to demographic and environmental variables
In the Bernard group's study of 226 children in BrusselsBrussels
Brussels , officially the Brussels Region or Brussels-Capital Region , is the capital of Belgium and the de facto capital of the European Union...
and the Ardenne region in 2003, asthma and exercise-induced bronchoconstriction (a test related to potential breathing difficulties) were not found to have any statistically significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
correlation with the demographic and environmental factors of age, sex, ethnic origin, socioeconomic status or exposure to pet
Pet
A pet is a household animal kept for companionship and a person's enjoyment, as opposed to wild animals or to livestock, laboratory animals, working animals or sport animals, which are kept for economic or productive reasons. The most popular pets are noted for their loyal or playful...
s or passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...
alone. However, when the time spent at chlorinated swimming pools (modified for pool height as a statistical way to indicate likely concentrations of chlorine related gases) was adjusted for exposure to pets and passive smoking, the significance of the correlations with asthma increased further. The authors describe this saying that a "very strong argument in [favour] of causality [between pool attendance and asthma] comes from the synergistic action of exposure to pets and [passive smoking], two well documented risk factors for asthma, which together considerably increase the strength of the associations, to levels largely above those usually observed in asthma epidemiology."
In a later study by the Bernard group of 190,000 children in 21 countries in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, it was found that 13 to 14 year old children were 2% to 3.5% more likely to have or have had asthma for every additional indoor chlorinated pool per 100,000 inhabitants in their place of residence. Other atopic
Atopy
Atopy or atopic syndrome is a predisposition toward developing certain allergic hypersensitivity reactions.Atopy may have a hereditary component, although contact with the allergen must occur before the hypersensitivity reaction can develop ....
diseases such as hay fever
Hay Fever
Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...
or atopic dermatitis
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...
were found to be not associated with the presence of the pools. The association of asthma with the number of indoor chlorinated swimming pools per 100,000 inhabitants was found by the authors to be independent of altitude
Altitude
Altitude or height is defined based on the context in which it is used . As a general definition, altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The reference datum also often varies according to the context...
, climate
Climate
Climate encompasses the statistics of temperature, humidity, atmospheric pressure, wind, rainfall, atmospheric particle count and other meteorological elemental measurements in a given region over long periods...
, and GDP per capita.
Scientific debate on the epidemiological studies
After the publication of Bernard's group's 2003 study, B. Armstrong and D. Strachan described the study as "generally well conducted", but stated that some aspects of the statistical analysis and interpretation were "misleading", to the extent that "the epidemiological association of asthma with swimming pool use [was] not as strong as claimed by the authors".Following publication of Bernard's group's 2006 study, some concerns by P.A. Eggleston and a response by Bernard's group were published. For example, Eggleston argued that if "chlorinated compounds at indoor swimming pools could cause asthma", then "frequent and longer exposures at home" should be even stronger causes of asthma, in contradiction to the available evidence from a single group of children. Bernard's group's response was that while children at an indoor chlorinated pool "actively inhale [the chlorination products] as gases, aerosols, or even water", they are not usually involved in household cleaning tasks, so they could benefit from the hygienic effects of the chlorine based cleaning products while avoiding any significant contact with the related gases. Members of Bernard's group's declared that they had no potentially conflicting financial interests, while Eggleston declared that he had received money from the United States based group called the Chlorine Chemistry Council. In a "Faculty Disclosure" statement in an asthma-related publication, it was declared that Eggleston is "a consultant for Chlorine Chemistry Council, Church and Dwight
Church and Dwight
Church & Dwight Co., Inc. is a minor U.S. manufacturer of household products that is based in Princeton, New Jersey. While it manufactures many items, it is by far best known for its Arm & Hammer line which includes baking soda and many other items made with it. The company was founded in 1896 to...
, Merck Sharp & Dohme
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
, and Procter & Gamble
Procter & Gamble
Procter & Gamble is a Fortune 500 American multinational corporation headquartered in downtown Cincinnati, Ohio and manufactures a wide range of consumer goods....
, and is on the speakers' bureau for AstraZeneca
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
, GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
, and Merck."
Hypothesised mechanistic explanation
Alfred Bernard and colleagues argue that what is common to the pool chlorine hypothesis and epidemiological studies associating chlorine based irritants to atopyAtopy
Atopy or atopic syndrome is a predisposition toward developing certain allergic hypersensitivity reactions.Atopy may have a hereditary component, although contact with the allergen must occur before the hypersensitivity reaction can develop ....
could be that frequent, long-term disruption of the epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
of the lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
, which normally provides a protective barrier against various pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s, could allow allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
s to cross this barrier. This process would also cause certain protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s from the lung epithelium to have increased blood serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentrations.
Relation to the hygiene hypothesis
Independently of their own research results, Bernard and his colleagues have suggested that the hygiene hypothesisHygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
still lacks a close causal link with asthma, and that the hygiene hypothesis might be most relevant for a restricted number of types of infections, such as those due to parasites.