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MagazineJanuary 2011 (Vol. 21 Issue 10)Asthma

Rates of asthma- especially in children-have increased dramatically over the past three decades, and scientists around the world have been trying to figure out why

Rates of asthma- especially in children-have increased dramatically over the past three decades, and scientists around the world have been trying to figure out why.
Now, researchers from New Zealand have discovered an alarming link between childhood asthma and the use of paracetamol (acetaminophen), which may help to shed some light on the so-called asthma epidemic.

The study, led by Professor Julian Crane of Otago University in Wellington, tracked almost 1500 children as part of the New Zealand Asthma and Allergy Cohort Study. Using data collected from the children's mothers, the study aimed to investigate whether or not there was any association between the use of paracetamol in infancy, and the development of asthma and allergic sensitivity at around the time of starting kindergarten.

The major finding of the study was that children who used paracetamol, which is found in products such as Calpol and Benilyn, before the age of 15 months-a whopping 90 per cent of cases-were twice as likely to develop symptoms of asthma at six years of age as children who had not been given paracetamol. Those given paracetamol were also more than three times more likely to develop sensitivity to allergens such as cow's milk and animal hair, as determined by skin-prick allergy tests (Clin Exp Allergy, 2010 Sep 29; Epub ahead of print).
Although these results are not proof that paracetamol can cause asthma, the researchers noted that the connection between the two was dose-dependent-the more paraceta-mol taken, the greater the risk of asthma-a finding that is consistent with a causal interpretation.

What's more, the results add to a growing body of research associating the use of paracetamol with asthma, especially in children, demonstrating that this is not just a one-off finding.

Indeed, two years ago, Professor Crane and scientists from the Medical Research Institute of New Zealand published results from the third phase of the International Study of Asthma and Allergy in Childhood (ISAAC), so far the largest study to examine the paracetamol-asthma connection. It involved more than 200,000 children in 31 countries aged between six and seven years. Their parents filled in written questionnaires regarding how often they had given their child paracetamol (during the past year and in the first year of life), and describing the symptoms of a number of diseases, including asthma, rhinoconjunctivitis (a combination of a runny nose and swelling or infection of the eyelids, such as seen in hay fever) and eczema.

The results showed that children were significantly more likely to have asthma if they were given paracetamol during their first year of life. Also, current paracetamol use was associated with an increased risk of asthma in a dose-response relationship-meaning that the moderate use of paracetamol increased asthma risk by 61 per cent, while high use was associated with an increased risk of around 300 per cent.

The researchers concluded that "exposure to paracetamol might be a risk factor for the development of asthma in childhood". Paracetamol also appeared to increase the risks of rhinoconjunctivitis and eczema (Lancet, 2008; 372: 1039-48).
Other studies have also found a link between this commonly used drug and childhood asthma. Worryingly, there is even evidence to suggest that exposure to paracetamol before birth can have a significant impact.

One such study involved more than 66,000 women from the Danish National Birth Cohort, and discovered that those who used paracetamol during pregnancy were more likely to have a child who suffered from asthma or wheezing. The highest risks were seen in women who used paracetamol during the first trimester of pregnancy, which led to a 45-per-cent greater risk of having a child with persistent wheezing (Int J Epidemiol, 2008; 37: 583-90).

These results are supported by a study of African-American children and those from the Dominican Republic living in New York that suggested that children exposed to paracetamol prenatally were more likely to have asthma symptoms at age five (Thorax, 2010; 65: 118-23).

There's also evidence of a link between asthma and paracetamol in other age groups. Most recently, the results of the large-scale ISAAC study showed that teenagers (more than 300,000 in 50 countries) who used paracetamol were more likely to suffer from asthma symptoms. High use (at least once in the past month) more than doubled the risk of symptoms, but even medium use (at least once during the past year) significantly boosted the risk (Am J Respir Crit Care Med, 2010 Aug 13; Epub ahead of print).

Another study found that frequent use of paracetamol was associated with asthma in adults aged 16-49 years. Again, the relationship was clear: the more often the use of paracetamol, the higher the risk of asthma (Thorax, 2000; 55: 266-70).
Certainly, there's something going on here that's more than just coinci-dence.
Indeed, some researchers are now even suggesting that the international trend towards increased paracetamol use may be behind the rising rates of asthma over the recent decades (Clin Exp Allergy, 2010; 40: 32-41).

But by what mechanism could this popular painkiller be causing asthma in children and adults?

One theory is that paracetamol might reduce levels of the antioxidant glutathione in the lungs, which is needed to defend the delicate airways against harmful pollutants and irritants (Clin Exp Allergy, 2010 Sep 29; Epub ahead of print; Thorax, 2000; 55: 266-70).

Although more research is needed, so far, the evidence suggests that limiting the use of paracetamol might be an important step towards preventing asthma and asthma symptoms.

Other possible causes

In addition to paracetamol, a range of other drugs and chemicals has been linked to an increased risk of asthma in recent years.

o Antibiotics. Data from the ISSAC study revealed that children given antibiotics during the first year of life were nearly twice as likely to have asthma at age six or seven. As with paracetamol, antibiotics were also associated with a greater risk of rhinoconjunctivitis and eczema (J Allergy Clin Immunol, 2009; 124: 982-9).

o Hormone replacement therapy (HRT). Menopausal women taking oestrogen-only HRT were found to have a higher risk of developing asthma symptoms for the first time postmenopausally (Thorax, 2010; 65: 292-7). Indeed, an earlier study had reported similar findings (Am J Respir Crit Care Med, 1995; 152: 1183-8).

o Household chemicals. A number of studies have found a connection between chemical-based domestic products and asthma in both adults and children. Sprayed products such as air-fresheners appear to be the most risky (Am J Respir Crit Care Med, 2007; 176: 735-41).

o Chlorine. Exposure to chlorinated swimming pools has also been linked to the development of asthma. One study found a significant association between the number of years a boy had been swimming, and his likelihood of having wheezing and being diag-nosed with asthma (Ir Med J, 2009; 102: 79-82).

o Air pollution. Children living near busy roads have a greater risk of asthma and other allergic disorders, according to a German study involving around 3000 children at ages four and six years (Am J Respir Crit Care Med, 2008; 177: 1331-7).

o Tobacco smoke. Exposure to tobacco smoke is a well-known risk factor for childhood asthma. One study found that children exposed both before and after birth to tobacco smoke were significantly more likely to be diagnosed with asthma, and to suffer from persist-ent wheezing and other respiratory problems (Arch Bronconeumol, 2009; 45: 585-90).

The dietary link

On the other hand, the increasing prevalence of asthma might be related to diet-particularly in the developed countries. A study of more than 50,000 school children between 1995 and 2005 found that eating three or more burgers a week significantly increased the risk of asthma. In contrast, the so-called Mediterranean diet, rich in fruit, vegetables and fish, appeared to have protective effects (Thorax, 2010; 65: 516-22).

The authors pointed out that fruit and vegetables are rich in antioxidant vitamins and biologically active agents, while the omega-3 fatty acids found in fish have anti-inflammatory properties, so these are biologically plausible reasons for the latter findings.

However, the burger connection is not as easy to explain. It may just be that frequent burger consumption is a marker of an unhealthy lifestyle that may be increasing the risk of asthma.
Whatever the mechanisms, as with the studies linking asthma with paracetamol, and other drugs and chemicals, the findings of this study suggest the possibility that asthma-particularly childhood asthma-can potentially be prevented.

Joanna Evans

Complementary and alternative treatments

o The Buteyko breathing technique. This method, which involves a series of specific breathing exercises, is now a well-established complementary therapy for asthma. Randomized controlled studies show that it can significantly reduce the use of prescription drugs in asthma sufferers (Respir Med, 2008; 102: 726-32; N Z Med J, 2003; 116: U710).

o Acupuncture may be useful for some asthma sufferers. A recent meta-analysis (using pooled results) of 22 trials, involving more than 3000 cases of asthma, reported that the total effective rate with acupuncture was significantly superior to using a control (Zhongguo Zhen Jiu, 2010; 30: 787-92).

o Yoga, which teaches both breathing exercises and relaxation techniques, appears to be helpful for asthma. One trial in patients with bronchial asthma found that yoga breathing exercises used in conjunction with standard drug treatment significantly improved lung function compared with a control (Indian J Physiol Pharmacol, 2009; 53: 169-74).

o Biofeedback techniques, which use special devices to feed back information related to specific internal physiological states, have long been recommended as a complementary therapy for asthma. One study found that heart rate variability (HRV) biofeedback used alongside steroids markedly improved lung function and asthma severity compared with steroids alone or steroids with a placebo treatment. Patients using HRV biofeedback also needed less medication (Chest, 2004; 126: 352-61).

o Supplements. The following nutritional supplements may be worth a try.

o Vitamin C. A double-blind trial found that vitamin C supplementation (1 g/day for 14 weeks) reduced the severity and frequency of attacks among Nigerian adults with asthma (Trop Geogr Med, 1980; 32: 132-7). More recently, US researchers reported that 1500 mg/day may be of benefit to people with exercise-induced asthma (Respir Med, 2007; 101: 1770-8).

o Magnesium. Low intakes of this mineral have been linked with asthma. In a recent trial of men and women with mild-to-moderate asthma, supplementing with
170 mg twice a day for six months led to reduced bronchial reactivity, as well as improvements in asthma control and quality of life (J Asthma, 2010; 47: 83-92).

o Selenium. Asthma involves free-radical damage that selenium, a potent antioxidant, may be able to protect against. A small, double-blind study found that supplementing with 100 mcg/day of sodium selenite (a form of selenium) for 14 weeks resulted in clinical improvement in six out of 11 patients compared with only one out of the 10 taking a placebo (Allergy, 1993; 48: 30-6).

o Fish oil may be of benefit to asthmatics, according to some evidence. In one trial, children who received 300 mg/day of fish oil (providing 84 mg of EPA and 36 mg of DHA) showed significant improvements in their asthma symptoms. However, these benefits were observed in a hospital situation where exposure to food and environmental allergens was being kept strictly under control (Eur Respir J, 2000; 16: 861-5).

In addition, a combination of omega-3 fatty acids, vitamin C and zinc was recently found to improve lung function and asthma control in children with moderately persistent asthma. In this study, although each supplement had beneficial effects on their own, all three taken together in combination had the greatest impact (Acta Paediatr, 2009; 98: 737-42).

o Herbs, such as Amrita Bindu, an Ayurvedic salt-spice herbal preparation, was effective against asthma in one study. Children with severe asthma were given 250-500 mg (depending on their age) of this remedy twice daily after meals. After three months, most of the children were able to stop their prescription antiasthma medications and were no longer suffering from asthma attacks (J Ethnopharmacol, 2004; 90: 105-14). However, we don't know to what extent these results were due to the placebo effect.

A number of other herbal formulas may also be useful against asthma, including ivy-leaf extract, powdered picrorhiza root and Ginkgo-leaf tincture. For best results, consult a qualified medical herbalist.

VOL. 21 NO. 10

In vino veritas

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