Prevalence and new onset of chronic phlegm and chronic productive cough among the centres of the ECRHS in both males and females vary by a factor of three, but these variations were not explained by the average levels of PM2.5. However, at the individual level, self‐reported traffic intensity and home outdoor levels of NO2 (a surrogate of traffic exposure) were associated with frequency of chronic phlegm and chronic productive cough in females homogeneously throughout the centres. Fitting either prevalence or new onset of chronic phlegm at the end of follow up yielded similar findings. The persistence of the effect of traffic intensity in non‐smokers reinforces the validity of this finding, as well as the fact that NO2 was measured in subjects who had not moved residence since baseline and also that the findings were homogenous across the geographical areas.
Measurement of individual exposure is the greatest challenge of population studies on air pollution. A central monitoring measurement does not reflect the individual variability within a community for primary tail pipe emissions,26
particularly in large cities as many of those participating in ECRHS. This probably explains the apparent inconsistency of a lack of effects using centre‐level measurements and a presence of effects when using individual measurements. An exception could be the S content, which is expected to be homogeneously distributed in a city because it reflects long range transport pollution. However, we also did not find an association with S content. In addition to the potential variation in the S content within individuals from the same city because of different time‐activity patterns, social and cultural heterogeneity in Europe is probably too large to be adjusted for in the hierarchical models, in contrast to studies carried out in more homogeneous areas such as the SAPALDIA study.15
Moreover, non‐response might have heterogeneously biased the prevalence as centres with higher pollution showed higher non‐response. Overall, a true ecological association could have been underestimated.
The assessment of the cumulative exposure at home outdoors is a major challenge when the time between exposure and effect assessment is long. A measure of a single period does not capture the seasonal variations while the average of at least two periods of measurement notably reduces the error in relation to the yearly average. The deployment of home NO2 samplers across seasons happened randomly with subject selections based neither on health nor local air quality characteristics. Thus, we expect that the use of a single or a few NO2 sampling periods as an estimate of the annual means introduced random rather than systematic errors with a bias most likely towards null findings. The lack of comparable monitoring data for the time up to ECRHS II is an inherent weakness of the study. As a consequence, we are unable to investigate the effect of changes in air quality between ECRHS I and II and its effects on the development of respiratory diseases. However, the relevant period of reported symptoms, namely the 12 months before the follow up assessment and the ECRHS II air quality assessment, are very well matched and valid to investigate the hypothesis.
At high concentrations in animals and humans, NO2
damages the epithelial cells by oxidant injury, reduces the clearance of infecting organisms, depresses alveolar macrophages, and releases pro‐inflammatory mediators.27
The toxicological evidence suggests that NO2
at the low concentrations found in everyday life may play a role in lung inflammation.28,29
Both a recent Dutch birth cohort30
and a German birth cohort31
showed an association of respiratory symptoms in infants with outdoor NO2
measurements, something which has also been observed in studies of school age children.32,33
In contrast, cohort studies measuring indoor NO2
did not find an association.34,35
Furthermore, in a Swiss study, the duration of lower respiratory symptoms in children less than 5 years of age was related to an individual outdoor measurement, but not with indoor levels.36
Similarly, the effect of home outdoor NO2
was associated with an increase of wheeze in a German study in 317 children, which was not found with personal NO2
These studies suggest that outdoor NO2
per se is probably only a surrogate of the pollutant mixture responsible for chronic respiratory effects, while substances such as polycyclic aromatic hydrocarbons or diesel particles may be the most important aetiological components. It has been shown that the concentration of fine particulate matter varies with nearby traffic roads and with NO2
The role of traffic exposure, mostly fine particulates, in chronic bronchitis is consistent with experimental findings that generated free radicals are capable of causing cell oxidative stress and lung inflammation.39
An inflammatory pathway correlates with the persistence of the observed effects seen in this study after excluding individuals with asthma, suggesting that traffic effects a respiratory phenotype, defined by reporting of chronic respiratory symptoms—even in non‐smokers.
In our study, a simple measure of self‐reported traffic intensity, whether cars or trucks and buses (we did not find differences between the two items, data not shown), was associated with chronic phlegm and chronic productive cough as was the individual measure of NO2
. In fact, we found a strong correlation between reported frequent or constant traffic and the home‐outdoor NO2
levels (an increase of 40% in the NO2
levels in comparison with those reporting no traffic). However, evidence of the poor value of reported traffic40
and the impossibility of assessing the potential role of reverse causation between symptoms and reporting of traffic means the findings on traffic intensity must be viewed with caution.
A major finding is the gender differences in traffic effects (when measured either as a report of traffic intensity or as an individual level measurement of NO2
) consistent with results from a small study in Sweden which found an association between NO2
and chronic cough only among women.41
One explanation is that home NO2
and traffic reflects the personal exposure among women but not among men given the potential for women to spend longer periods at home. On average women spend more time at home than men, according to the EXPOLIS study in several cities in Europe (N Kunzli, personal communication). Another explanation, though less likely, is that females are more susceptible to air pollution. Differences in susceptibility factors (hormones), risk factors (smoking), perception of the disease, and access to health services have been related to sex differences in asthma prevalence and chronic obstructive pulmonary disease (COPD).42
In a cohort of individuals with COPD, females had a higher risk of dying in relation to particle levels than males.43
A recent study has shown different mechanisms between males and females in the development of asthma, females being more affected by non‐atopic mechanisms.44
A third possible explanation could be residual confounding by smoking but analysis among never smokers did not show any association in males, while the association among females of both traffic and NO2
did not change. A final explanation refers to the question of whether women have better/different perceptions of their environment and their symptoms. The fact that we observed the same association between NO2
and reporting of intensity of traffic in women and men, homogeneously across all centres, seems to suggest a similar perception of traffic intensity. In addition, the consistency of the findings—regardless of whether chronic bronchitis was defined by chronic phlegm or chronic productive cough (or chronic cough, data not shown)—reduces the potential for a differential diagnostic bias in women compared with men. Finally, the finding of a stronger association with NO2
among the more educated women and the non‐manual social class possibly was due to a more valid perception and reporting of symptoms of chronic bronchitis, given that the variations in NO2
levels in our study were not perceivable.
One strength of the present study, in addition to the individual measurement of air pollution, is the prospective nature of the design. That allowed consideration of two potentially different symptomatic groups, namely those with symptoms at baseline, and those with symptoms only at follow up (“new onset”). The repeated survey showed a high fluctuation in chronic bronchitis symptoms, something which has also been shown with other respiratory symptoms.45
In light of temporal changes in occurrence and reporting of symptoms, the questionnaire captures in particular symptomatic episodes during the past year or months before the two surveys (ECRHS I and II) rather than a “chronic condition”. Accordingly, “new onset” may not necessarily reflect the incidence of a chronic condition not present at ECRHS I, but the period prevalence of recent symptomatic episodes among those who did not report symptomatic episodes 7–10 years before. The group with symptoms reported in both surveys may more likely consist of subjects with chronic conditions. The findings of an association of exposure during ECRHS II with symptom prevalence in the total population, as well as in those who did not report symptoms in ECHRS I, suggests that air pollution may contribute to symptomatic episodes not only in those with underlying chronic respiratory diseases. The high turnover of incident and remitting cases in our study suggests that the predictive nature of having chronic bronchitis symptoms at middle age is uncertain. The present results may refer to the acute and subchronic, rather than chronic, effects of air pollution. To investigate the contribution of ambient pollution on the chronic development of symptomatic respiratory diseases one may need longitudinal studies with several annual repeated surveys, coupled with continuous monitoring across the entire follow up.
A limitation of the present study in the assessment of the individual exposures (that is, traffic, NO2
) was the non‐response rate, however the consistency of the coefficients after adjusting for the odds ratio between non‐response and symptoms and the geographical homogeneity of the findings are reassuring in this respect. Non‐response is notable for the home NO2
measurement, however participants had the same prevalence of chronic productive cough (p
0.7) and chronic phlegm (p
0.5) than non‐participants, which reduces the probability that association with NO2
was due to a selection bias. In addition, it seems unlikely that NO2
effects were driven by a selective participation of diseased females, because there was no association between participation and symptoms among females (p>0.4).
We performed a hierarchical analysis in order to incorporate the geographical structure of the data and to incorporate contextual (that is, aggregated) variables, related with air pollution, and with chronic bronchitis, such as the smoking patterns by area. Thus, we adjusted for social conditions and occupation not only at the individual level, but also at the aggregated level in order to avoid an imperfect control of the confounding. We found that inclusion of aggregated variables did not change our estimation of the effect of traffic among females, and also that geographical variations in chronic bronchitis were only moderately explained by known risk factors, as already found in the cross sectional analysis of ECRHS I.46
Overall, chronic bronchitis symptoms increased among females in relation to indicators of exposures to traffic pollution at the home level, reinforcing public health concerns about the health effects of urban air pollution emissions, and provoking unsolved questions about gender differences in bronchitis and susceptibility to air pollutants.