Asthma and Swimming Pool Chlorination
Swimming splashed to the forefront of sports coverage over the last month with Michael Phelps' performance in the 2008 Olympics in Beijing. Participants improve cardiovascular fitness, work upper and lower body muscle groups and find entertainment in the pool. In addition, according to widely held beliefs, many physicians consider swimming beneficial for the pulmonary function of asthmatics. Attention was first drawn to asthmatic swimmers following the 1972 Olympics when the gold medal winner in the 500 meter freestyle tested positive for ephedra and theophylline, banned substances used in the treatment of asthma.
Current evidence clearly suggests that dry, cold air is
a precipitant for asthma in susceptible individual[i]. Following logic, one would expect that
warm, most pool air would improve pulmonary function and decrease
symptoms. This theory was first
described to me by an attending physician on my medicine rotation. Initial investigation of traditional
texts ascribe to this logic and advise that asthmatics partake in swimming
A number of studies have shown a general association between swimming and asthma[ii],[iii]. One such study by Helenius and Haahtela studied the prevalence of asthma in 42 competitive swimmers, 49 power athletes, and 71 distance runners compared to 45 controls using symptom surveys, pulmonary function tests, skin patch testing, and histamine challenge[iv]. Results show the prevalence of current asthma (defined by increased bronchial responsiveness to histamine and asthma symptoms in the last year) is 26% in swimmers, 7% in distance runners, 12% in power athletes and 4.3% in controls. Additionally, 50% of swimmers had 1 or more positive reactions to skin allergen test and 29% reporting hay-fever symptoms. These results are comparable to those found in other athletes, but greater than observed in controls. Actually, the prevalence of asthmatic swimmers was also described to me as support for water improving lung function, as asthmatics would tend to succeed in swimming. Makes sense.
Unfortunately, this is not the whole story. Sanitation standards require treatment of the pool with chemicals to decrease the burden of infective agents. Over the last decade, evidence has accumulated that suggests cleaning chemicals, namely chlorine and its derivatives, cause asthma symptoms and airway hyper-reactivity. The rest of this paper will discuss this chicken-or-the-egg relationship between asthma and swimming; whether swimming draws asthmatics to it, or creates them.
Before discussing chlorine's relationship with asthma in swimmers, it is important to understand the different chemicals involved in the treatment of pools. Many treatments are available, including chlorine based products (chlorine gas, hypochlorite, and chlorinated isocyanurates) and non-chlorinated products (Bromide, UV, O3, and silver and copper ionizing systems,). Chlorine based products predominate because of their availability and low cost. The recommended chlorine concentration in pools is 2.0 - 4.0 ppm. Once added to water, chlorine produces hypochlorous acid (HOCl), which is the active compound. Hypochlorous acid is highly reactive, and when it combines with amines and proteins from human skin and urine, chloramines are produced (nitrogen trichloride, dichloride and monochloride). Chloramines give the air around the pool its characteristic “chlorine” odor and are considered a leading candidate as the cause for pulmonary symptoms in swimmers. Other known chemicals found above chlorinated pools include free chlorine, chloroform, formaldehyde, acetaldehyde, and halogenated hydrocarbons.
A few basic exposure related asthma definitions help establish framework for characterizing this relationship. Occupational asthma is defined as obstruction, hyper-responsiveness and inflammation resulting from a workplace stimulus, in patients without preexisting asthma. It may be an immunologic stimulus (“occupational asthma”) with a latency period or a non-immunologic stimulus (“irritant-induced asthma”) without latency. Patients with a history of atopy, smoking or family history may be predisposed to developing “occupational asthma.” Low molecular weight chemicals, similar to products of chlorination, can cause “occupational asthma” via neoantigen production from hapten and endogenous protein.
Important in differentiating these conditions, “occupational asthma” can be reproduced via challenge test while irritant-induced asthma cannot. Patient's with “occupational asthma” become symptomatic with exposure and symptoms typically resolve once the stimulus is removed. Patients with irritant-induced asthma exhibit hypersensitivity to histamine, while patients with “occupational asthma” may not. Work-aggravated asthma is preexisting asthma that is exacerbated in the work-place. A relationship between swimming and asthma exists, the question is if it is irritant-induced asthma, “occupational asthma” or preexisting asthma.
Reactive airway dysfunction syndrome (“RADS”) is a constellation of prolonged airway symptoms, including asthma, that follow a single acute exposure to a toxic chemical and develop usually within 24 hours. Asthma symptoms, airflow obstruction on spirometry and increased sensitivity to methacholine are all characteristic of RADS both acutely and after three years of follow-up. RADS is considered a dramatic acute presentation of irritant-induced asthma, which coexist along a spectrum. Many products of chlorination are known causes of RADS such as ammonias, bleach, chlorine, chloroform, formaldehyde and acetaldehyde. Implicating these same chemicals in the more insidious onset irritant-induced asthma would be a logical following step. Until recently however, little has been documented linking chronic low level exposures to symptoms.
With many chemicals liberated when chlorine is added to the pool as described above, research has been conducted to identify causative chemicals. Of these chemicals, nitrogen trichloride (NCl3) has been identified as a possible candidate, generating much attention. A small study conducted by Thickett et al. examined airway responsiveness to this specific byproduct in 2 indoor swim-pool employees[v]. Both had a negative response to histamine challenge and a negative response to chlorine evolved from sodium hypochlorite in water (no chloramines). Both employees were challenged with nitrogen tricholoride at a concentration commonly found above pools, with a drop in FEV1 of – 45% predicted and – 27% predicted from a normal baseline. These findings are consistent with “occupational asthma”, with latency rather than irritant-induced asthma.
Although nitrogen trichloride is one possible cause for airway hyper-responsiveness in the pool and shortly after swimming, other mechanisms likely exist that confer an irritant-induced asthma picture. Nitrogen trichloride may eventually be found to cause irritant-induced asthma, however many studies reviewed in writing this paper, incorrectly site the above paper by Thickett as a definitive cause. Subsequent studies specifically implicating nitrogen trichloride in an irritant-induced asthma picture are either critically flawed[vi] or do not support the hypotheses[vii]. Specifically, the 2007 study of 624 pool workers by Jacobs et al. correlates pool nitrogen trichloride levels with increased respiratory symptoms; however, levels of other products of chlorination were not controlled for, nor was a correlation specified between asthma symptoms and nitrogen trichloride levels. Additionally, exposure to sodium hypochlorite in cleaning products has been associated with irritant-induced asthma and chronic bronchitis[viii], supporting the role of other causative agents. That said, nitrogen trichloride is a strong oxidizing agent and could very well be a contributing agent.
Specific causative chemical aside, the underlying pathology for observed symptomatic changes in swimmers has also been explored. Based on current findings, damage to the normal lung barrier function as well as intrinsic hypersensitivity to the chemicals could be involved. Damage to the lung epithelia may directly lead to irritant-induced asthma and increased sensitivity to methacholine. Additionally, break down of the lungs normal barrier function may predispose patients to foreign antigen sensitization, offering an explanation for increased prevalence of atopy as well as asthma in swimmers.
Evaluation of in vitro studies put in vivo studies in focus. Products of chlorination, hypochlorous acid and chloramines are powerful membrane penetrating oxidants that react with cytoskeletal and extracellular matrix proteins of the endothelium and epithelium. Confirmed in vitro, both hypochlorous acid and chloramines disrupt the cytoskeleton, cause cell retraction, and disrupt cellular junctions, with subsequent increase endothelial or epithelial permeability[ix],[x]. Similar changes follow infectious inflammation with activation of myeloperoxidase and release of activated chlorine species[xi]. This in vitro damage is observed at hypochlorous acid and chloramine concentrations similar to chlorinated pool water. These changes would be consistent with irritant-induced asthma or increased permeability leading to foreign antigen exposure and asthma.
To investigate possible lung damage in swimmers, Birgitta et. al. examined the plasma epithelial marker of lung injury CC16 (clara cell protein 16) in children regularly exposed to chlorinated pools[xii]. Clara cell protein 16 is secreted by clara cells, found in the bronchioles of the lungs. Clara cells are non-mucous secreting, non-ciliated cells that detoxify chemicals via the CYP 450 system, secrete enzyme and surfactants to protect the pulmonary epithelia. Clara cell protein 16 is used as a marker for lung injury and epithelial integrity. Levels are increased shortly following acute exposure to toxins such as ozone leading to increased epithelial permeability. On the other hand, low levels of this marker of are observed in patients with chronically damaged lungs such as smokers, chronic bronchitis, and silica exposure, secondary to clara cell dysfunction or damage. CC16 is considered a sensitive marker of injury as changes in serum levels can be observed prior to significant clinical loss of function. In this study, a statistically significant decrease in CC16 was observed between children regularly engaged in swimming compared to those without exposure to pools.
These authors also measured FEV1 % predicted, finding no difference between those children regularly exposed to swimming pools and controls. Although this does not support the role of chlorinated pool induced asthma, these children aged 10-11, averaging 4 hours/month in the pool have limited exposure compared to pool employees or competitive swimmers. Correlating negative PFTs with decreased CC16 levels suggests that the lung damage may be in a pre-clinically evident phase.
Alterations in serum markers of pulmonary integrity have been echoed by authors Bernard in 2003[xiii] and Carbonelle in 2002[xiv]. Exposure to products of chlorination in children was correlated to elevated levels of surfactant A and B, signifying lost epithelial integrity, on the level observed in smokers. Serum IgE level, a marker for developing asthma, was positively related to serum surfactant level suggesting a break-down of epithelial integrity may predispose children to asthma.
Oxidative stress is one logical mechanism proposed for the damage observed in the lungs of swimmers, and examined by authors Varraso et al[xv]. In their study they evaluated serum oxidative markers in competitive swimmers who have not been engaged in training for at least 2 weeks, then followed these swimmers for a period of 24 weeks of training. Using multivariate analysis, the authors found a significant increase in superoxide dysmutase and glutathione peroxidase associated both with the rigor of exercise and with exposure to products of chlorination. Differences were not observed in ferritin, ceruloplasmin, or antioxidant levels. Although there is no way to differentiate skin absorption from pulmonary inhalation, oxidative damage caused by oxidizing agents in the lung is a reasonable etiology.
Interestingly, Varraso et al. examined the prevalence of pulmonary symptoms in these competitive swimmers and compared them to a control group of lifeguards, also exposed to products of chlorination, but not to the extent of competitive swimmers. They found a significantly increased prevalence of irritant nasal symptoms, throat irritation, and asthma. Further support for chlorination induced symptoms, and suggesting a dose relationship.
Sputum analysis of competitive swimmers has been conducted, showing significant elevations in eosinophils and neutrophils[xvi],[xvii]. Lymphocytes were also elevated, but within normal limits. “Occupational asthma” is typically characterized by a similar increase in eosinophils and neutrophils. Chronic irritant-induced asthma is characterized by lymphocyte and eosinophil predominance with collagenous interstitial fibrosis. Traditional asthmatic sputum is characterized by an increase in eosinophils and lymphocytes; however, elevated neutrophils is also becoming recognized as characteristic. Although the cell differential doesn't definitively identify pathophysiology, it appears most consistent with irritant induced asthma.
The landmark epidemiological study in this field was conducted by Bernard and Nickmilder in 2007[xviii]. 190,000 European children aged 13-14 were evaluated for symptoms via written and video questionnaire. The study found a significant increase of 3.39% in wheezing symptoms and increase of 2.73% in asthma prevalence for every additional 1 chlorinated indoor swimming pool per 100,000 residents. Interestingly, the association was stronger in 13-14 year olds than in 6-7 year olds, suggesting cumulative exposure to chlorinated pools contributes to symptoms. This is independent of altitude, climate and income. No association was found between availability of swimming pools and hay-fever or atopy.
This study is extremely valuable as it identifies a direct risk of asthma with availability of swimming pools. On the other hand it does not characterize the amount of pool usage and quality of ventilation systems, often referenced as factors in asthma in swimmers. Likewise, the study fails to find an association with hay-fever or atopy, which is regularly identified in swimmers. One possible cause of discrepancy is frequency of pool use, a concept not addressed in the study. The fact that a pool may be available does not necessarily indicate that competitive or frequent swimming occurs. As products of chlorination are the suspected causes of asthma, actual exposure to these compounds resulting in disease would be a better study.
Prior to recent attention, USA Swimming estimated its enrollment of competitive swimmers at approximately 260,000 and increasing[xix]. A far greater number of people in this country and around the world spend a significant amount of time in the pool as physical therapy, entertainment and cross-training for other sports. According to 2005 CDC data, 7.7% of Americans have current asthma and an additional 3.5% have a lifetime diagnosis of asthma[xx]. The prevalence of asthma is increasing yearly in this and other industrialized nations, without a clearly defined cause. Swimmers appear to be at an increased risk of asthma and respiratory symptoms because of chlorine based cleaning chemicals, although the strength of this relationship is still debated. Experts have coined the term “the chlorine hypothesis” to describe this relationship, akin to the popular “hygiene hypothesis.”
Three mechanisms appear reasonable and may all play a role in this relationship. First, exposure to nitrogen trichloride leading to airway hyper-responsiveness is consistent with “occupational asthma.” Also, a non-specific irritant-induced asthma may result directly from chronic low-level damage to the lung, by products of chlorination. This is supported by positive correlation between products of chlorination and irritant-induced asthma, when chemicals examined in isolation. Damage to the epithelial lining of lung secondary to chlorination may lead to increased permeability and antigen exposure, consistent with the additional association with atopy and hay fever. Finally, preexisting asthma, has not been completely ruled out, although unlikely.
More studies need to be conducted in this field to help clarify the relationship between asthma and swimming, as current research is not definitive. One frequent flaw of existing studies is the lack of a truly comparable control group. A study evaluating asthma symptoms, PFT's, methacholine challenge, serum markers of pulmonary damage in swimmers training in both traditional chlorinated pools and alternatively treated pools (Bromine, UV, O3, etc.) would be valuable in identifying the chlorine treatment as culprit. Also, most current studies have limited enrollment. A larger study evaluating similar parameters in people prior to initiating competitive swimming, through their career, and into retirement would better support causation.
Although not the focus of this article, chlorine treatment has been associated with other health dangers such as miscarriage, colorectal cancer and bladder cancer secondary to chloroform content. The US government has acknowledged this association by recently limiting the chlorination of drinking water. No such legislation exists related to chlorine treatment of pools even though swimming for a period of 1 hour results in 93 times the exposure to chloroform as a glass of drinking water.
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