1 Unitat Recerca Respiratria i Ambietal, Institut Municipal Investigació Mèdica (IMIM), Barcelona, Catalonia, Spain
2 Universitat Pompeu Fabra, Barcelona, Spain
3 Pediatrics Service, Hospital del Mar, Barcelona, Spain
4 Area de Salud de Menorca, INSALUD, Menorca, Spain
5 Microbiological Department, Hospital Vall d'Hebron, Barcelona, Spain
6 Department of Occupational and Environmental Medicine, Imperial College, London, UK
Correspondence: Jordi Sunyer, IMIM, C/ Dr. Aiguader 80, 08003-Barcelona, Spain. E-mail: jsunyer{at}imim.es
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods Children (n = 1611) were recruited prior to birth for the Asthma Multicentre Infants Cohort Study (AMICS). Three concurrent cohorts (Ashford, Kent [UK]; Barcelona city, and Menorca Island [Spain]) followed the same research protocol. NO2 was measured with passive diffusion tubes placed in the living room for 2 weeks when infants were approximately 3 months old. Doctor-diagnosed LRTI during the first year of life (as well as antibiotic use) were measured by questionnaire, and in Ashford validated by the examination of clinical records. In Barcelona, direct measurements using nasopharyngeal lavage and cultures within a continuous surveillance system were done.
Results The cumulative rates of LRTI (39% in Ashford, 28% in Barcelona, and 45% in Menorca) were unrelated to NO2 levels (corresponding medians 6, 46, and 12 ppb, respectively) in all three centres (all odds ratios being around 1). Similarly, the rates of LRTI in Barcelona measured with the continuous record showed no association with NO2 (all rate ratios being below 1). In addition, there was no association between rate of antibiotics courses per year per child (2.4 in Ashford, 1.7 in Barcelona, 0.9 in Menorca) and NO2 levels.
Conclusions Indoor NO2 at current levels does not seem to be involved in increasing respiratory infections by itself in infants, suggesting that the effects observed in studies on outdoor air are probably due to other copollutants.
Nitrogen dioxide (NO2) is a common air pollutant both in homes and in the urban outdoor atmosphere. It is not highly soluble and most inhaled NO2 is retained in the small airways. Experimental studies have suggested that NO2 increases the effect of respiratory pathogens by reducing the efficacy of lung defence mechanisms (due to effects on mucocilliary clearance1 and the alveolar macrophage2), or by activating pro-inflammatory cells.3 The toxicological evidence suggests that NO2 at the low concentrations found in everyday life may play a role in increasing the incidence and severity of respiratory infections.3,4 In epidemiological studies, however, the evidence is controversial. In a follow-up study of a birth cohort in Albuquerque (New Mexico, USA) with a very comprehensive surveillance method to detect respiratory illness during the first year of life, indoor NO2 measurements were not associated with illness incidence.4 However, levels of NO2 were very low (median around 10 ppb) consistent with the low frequency of cooking with gas stoves in that community. By contrast, in a Dutch birth cohort, upper respiratory tract infections and doctor-diagnosed serious colds were related to NO2 outdoor levels.5 In two German birth cohorts, outdoor NO2 was associated with cough during the first year of life,6 and similarly in a panel study on infants with personal samplers in Finland.7 However, NO2 in outdoor air is mainly generated by traffic and the authors could not differentiate the role of NO2 from that of fine particles or other traffic pollutants.5,6 In indoor environments, NO2 is strongly related with indoor combustion sources associated with cooking or heating,8 and confounding by traffic pollutants is less of a limitation.
We aimed to assess the association between indoor NO2 and LRTI in a multicentre cohort study of newborn children with a broad range of indoor NO2 exposures.
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Exposure assessment
During the first 3 months of life a field technician made a home visit to complete a questionnaire on household characteristics (cooking appliances, heating and cooling systems, hours of ventilation, size of house), smoking and occupation, to collect dust samples, and to measure NO2. Average 2-week NO2 concentrations were measured by passive diffusion tubes9 installed in the living room wall at a height of 2 m and away from any window or air conditioner. NO2 concentrations were measured in a single laboratory by colorimetric reaction. Social class was defined using the UK Registrar General's 1990 classification of the current paternal occupation.
Respiratory infections
The frequency (and nature) of LRTI during infancy was obtained indirectly in all cohorts using maternal reports of upper and lower respiratory tract symptoms; as well as by systematic scrutiny of general practice medical and prescription records in Ashford. In all three centres, at the end of the first year, mothers were asked to record, retrospectively, the approximate frequency of symptoms consistent with upper or lower respiratory tract infection. Occurrence of an LRTI was defined as a positive answer to the question Has a doctor ever told you that your son/daughter has had a chest infection?. Information on antibiotic use was gathered using the question Has your son/daughter had any antibiotics? and if yes, how many times?.
In the Barcelona cohort, mothers were asked to contact a local 24-hour co-ordinating centre if their child should develop, during the first year of life, symptoms of an LRTI: wheezing, wet cough, or troubled breathing for at least one day. A standard symptoms form was then completed and a home visit made at which nasal and throat swabs were collected from the child after examination by a physician. Samples were cultured within the first 6 hours. A system of telephoned monthly reminders to all mothers in this cohort was instituted. Among 487 children, 462 (96%) provided data by the active method or the monthly recall.
Other measurements
At the enrollment mothers completed a questionnaire on previous diseases, allergic and respiratory symptoms, smoking, and occupation. A prick test to common allergens was carried out following standardized methods within AMICS, and classified as positive if it produced a skin wheal 3 mm (mean of perpendicular measures) in the presence of a positive histamine control and a negative uncoated control.
Data analysis
The cumulative incidence of LRTI during the first year of life was obtained from the one-year questionnaire. Similarly, LRTI data ascertained via the Barcelona surveillance system were treated as cumulative incidence. The association between LRTI and NO2 levels was measured with the odds ratio (OR), using logistic regression methods. It is assumed that the odds is an approximation of the cumulative incidence. Adjustment, then, could be evaluated using multivariate logistic regression models. Rates of antibiotic prescriptions, as well as incidence rate of LRTI in Barcelona were modelled with Poisson regression. Confounding variables selected were those showing a statistically significant association (P < 0.1) with LRTI in our study (i.e. ever breastfeeding, social class, sex, family size, and maternal smoking among a set of variables including parental asthma or atopy).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Misclassification of the outcome is unlikely to explain this lack of association, given the efforts made to ensure the quality of the diagnosis, in Ashford by checking the maternal reports with family practitioner clinical records, and in Barcelona by using a surveillance system and a direct method of evaluation of LRTI. Similarly no association was found with antibiotic use which may be an indicator of LRTI. However, the number of antibiotic courses is strongly related to social class and may indicate medical contact rather than actual LRTI or also other infections such as upper respiratory tract infections. Furthermore, no association was observed with any respiratory symptom at age one. Only data on the first year were examined, given that most incident cases occur in this period and further ascertainment is more complex. During this period, however, protection by breastfeeding should be taken into account. When we adjusted for length of breastfeeding (with a median length of 8 weeks among the 73% having breastfed) the results did not change.
Another potential bias could be a misclassification of exposure given that samples were collected only once. However, the results were very consistent with the use of gas appliances and a sub-analysis including only children home-bound throughout most of the year did not modify any of the results. In addition, indoor NO2 levels in this study have been strongly related to the type of gas appliance (i.e. higher levels with gas stove and heating)8 suggesting that the measurement error, if it exists, is small.
Overall, indoor NO2 at current levels does not seem to be involved in increasing respiratory infections by itself in infants, suggesting that the effects observed in studies on outdoor air are probably due to other pollutants.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Morrow PE. Toxicological data on NO2: an overview. J Toxicol Environ Health 1984;13:20527.[ISI][Medline]
3 Spannhake EW, Reddy SPM, Jacoby DB, Yu X, Saatian B, Tian J. Synergism between rhinovirus infection nad oxidant pollutant exposure enhances airway epithelial call cytokine production. Environ Health Perspect 2002;110:66570.[ISI][Medline]
4 Samet JM, Lambert E, Skipper BJ et al. Nitrogen dioxide and respiratory illnesses in infants. Am Rev Respir Dis 1993;148:125865.[ISI][Medline]
5 Brauer M, Hoek G, Van Vliet P et al. Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children. Am J Respir Crit Care Med 2002;166:109298.
6 Gerhing U, Cyris J, Sedlmeir G et al. Traffic-related pollution and respiratory health during the first 2 years of life. Eur Respir J 2002;19:69098.
7 Mukala K, Alm S, Tiitanen P, Salonen RO, Jantunen M, Pekkanen J. Nitrogen dioxide exposure assesment and cough among preschool children. Arch Environ Health 2000;55:43138.[ISI][Medline]
8 García-Algar O, Pichini S, Basagaña X et al. on behalf of the AMICS group. Concentrations and determinants of NO2 in homes of United Kingdom and Spain. J Air Waste Manage Assoc 2003;53:(in press).
9 Yanagisawa Y, Nishimura H. A badge-type personal sampler for measurement of personal exposure to NO2 and NO in ambient air. Environ Int 1982;8:23542.[CrossRef]
10 American Thoracic Society. Committee of the environmental and occupational health assembly. Health effects of outdoor pollution. Am J Respir Crit Care Med 1996;153:47784.[Abstract]
11 Samet JM, Utell MJ. The risk of nitrogen dioxide: what have we learned from epidemiological and clinical studies? Toxicol Industrial Health 1990;6:24762.[ISI][Medline]
12 Farrow A, Greenwood R, Preece S, Golding J. Nitrogen dioxide, the oxides of nitrogen and infants' health symptoms. Arch Environ Health 1997;52:18994.[ISI][Medline]
13 Magnus P, Nafstad P, Oie L et al. Exposure to nitrogen dioxide and the occurrence of bronchial obstruction in children below 2 years. Int J Epidemiol 1998;27:99599.[Abstract]
14 Van Vliet P, Knape M, de Hartog J, Janssen N, Harseema H, Brunekreef B. Motor vehicle exhaust and chronic respiratory symptoms in children living near freeways. Environ Res 1997;74:12232.[CrossRef][ISI][Medline]
15 Shima M, Adachi M. Effect of outdoor and indoor nitrogen dioxide on respiratory symptoms in schoolchildren. Int J Epidemiol 2000;29: 86270.
16 Braun-Fahrlander C, Ackerman-Lievrich U, Scwartz J, Gnehm HP, Rutishauser M, Wanner HU. Air pollution and respiratory symptoms in preschool children. Am Rev Respir Dis 1992;145: 4247.[ISI][Medline]