Chauhan, AJ, HM Inskip, CH Linaker, S Smith, J Schrieber, SL Johnston, and ST Holgate. 2003. Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Lancet 361: 1939-44.

In this paper Chauhan et al. report that asthma symptoms in children with viral infections are likely to be more severe if they are exposed to nitrogen dioxide (NO2), a common air pollutant. Adverse effects occur at air pollution levels 1/3rd of current WHO standards, indicating that standards should be strengthened.

Severe asthma attacks are the main cause of asthma morbidity and result in substantial health care costs. The number of children who died from asthma increased almost threefold from 1979 to 1996 and it is currently the third major cause of hospitalization in children under 15 years of age.

The Center for Disease Control has calculated that over 5 million people under the age of 18 are affected by asthma in the United States.

The estimated cost of treating asthma in those younger than 18 years of age is $3.2 billion per year and yet asthmatic children come in daily contact with NO2 through both indoor and outdoor sources such as cigarette smoke, gas cooking appliances, and motor vehicles. The alarming trends addressed in this study suggest current standards of NO2 pollution control should be reevaluated.

What did they do? Chauhan et al. studied a group of 114 asthmatic children ages 8-11 years old in the South Hampton area of the UK. For each child participating in the study, the scientists tracked NO2 exposures, respiratory symptoms and peak expiration flow (PEF).

The children wore special tubes on their outer clothing, changed every 7 days, to allow tracking of NO2 levels. Ambient concentrations outdoors were also obtained from a local monitoring station.

The scientists ranked each patient using a respiratory score based upon the severity of respiratory symptoms (cough, runny nose, etc.) using a scale ranging from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). For patients with a score of 4 or greater, they obtained a sample of nasal mucus which was then tested for the presence of viruses using a DNA technique called RT-PCR.

Once this analysis confirmed a viral respiratory infection, previously recorded symptoms were used to infer when it had begun. NO2 exposure levels were then estimated for the week before and after infection.

Together, these measurements then allowed analysis of the relationship between NO2 and severity of asthma attacks in children with proven viral infections.

Children who lived with smokers in the previous 12 months were excluded from the study. Additional factors considered in trend analysis included age, sex, social class, type of asthma medication taken, and whether gas or electric heating and appliances were used in the home of the participant.

What did they find? Viruses were confirmed in 78% of the infections reported. After tracking confirmed viral infections back to their date of origin, the research team calculated that median lower respiratory symptom scores increased from 1.1 to 2.1 in the week after infection, while median PEF rates decreased from 302 L/min to 286 L/min. So as symptoms worsened, asthma became more severe.

NO2 exposure levels for the week prior to infection were classified into three categories: low, medium, and high. Children in homes that used gas cooking had a median exposure of 12 µg/m3, whereas those in electric homes had a median exposure of 8.5 µg/m3.

Overall, children with higher exposures to NO2 in the week prior to infection had worse asthma symptoms, as measured by PEF. For each virus type except RS virus, PEF scores were lower when children had experienced higher NO2 levels. Thus in the graph to the left, red bars (high NO2 exposure) are lower than their matched blue bars (low NO2 exposure). The change for picornavirus was statistically significant. adapted from Chuahan et al. 2003

Infection severity (as measured by the respiratory score) increased with NO2 exposure. For a given virus infection, respiratory scores were worse with higher NO2 exposure. The change was statistically significant for all virus types together ('any virus') and for respiratory syncytial virus ('RS virus'). Higher scores of this lower-respiratory tract measurement reflect worse infection symptoms (see above). adapted from Chauhan et al. 2003.

Adjusting for confounding variables did not change these patterns.

What does this mean? Chauhan et al. have shown an association between increased personal exposure to NO2 and how severe asthma becomes in children with a respiratory virus infection.

Prior work had established NO2 exposure as a factor exacerbating asthma conditions. This study adds significant weight to the scientific evidence for that association. One of its main strengths was the use of personal air monitors, which allowed much better estimation of NO2 exposures. The authors observe that analysis of the personal monitoring data reveals a great deal of variation that would have been missed by other, older methods, thus weakening those earlier studies and decreasing their abilities to show an effect of the air pollutant.

Several mechanisms may be at work, including: direct impact of NO2 on the ability of airway cilia to clear mucus from the lungs, direct damage to the lungs, increases in inflammation factors, and enhanced allergenic activity. Damage may also be incurred indirectly through harm to the lungs immune system. Two in-vitro studies have supported the notion that NO2 exposure proceeding infection with respiratory syncitial virus and rhinovirus may make epithelial cells more susceptible to injury.

The increases in respiratory symptoms and decrements in lung function were not trivial. Higher NO2 levels were associated with more than a 2-fold loss in PEF performance compared to lower levels. Moreover, most of the patients were on asthma medication, reducing the severity of the symptoms overall. Finally, these effects were observed at NO2 levels well within the range experienced by many people.

Severe asthma conditions have a profound impact on public health as they account for the largest health costs associated with the disease. The World Health Organization recommends a NO2 annual average exposure of 40 µg/m3 as a safe threshold for public health. This study found significant adverse effects of NO2 at concentrations as low as 14 µg/m3 on asthmatic children with viral infections. These observations suggest that exposure standards for NO2 should be lowered. Decreasing exposures will both benefit asthmatics and decrease health costs.