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Revista chilena de pediatría

versión impresa ISSN 0370-4106

Rev. chil. pediatr. vol.90 no.2 Santiago abr. 2019

http://dx.doi.org/10.32641/rchped.v90i2.750 

ORIGINAL ARTICLE

Impact of Particulate Matter (PM 2,5 ) and children’s hospitalizations for respiratory diseases. A case cross-over study

Patricia Matus C.1 

Manuel Oyarzún G.2 

1 Public Health Department; Faculty of Medicine. University of Los Andes, Chile.

2 Pathophysiology Program. Institute of Biomedical Sciences. Faculty of Medicine. University of chile, Chile.

Abstract:

Introduction:

With seven million inhabitants, Santiago de Chile reaches high levels of air pollution in winter, the particulate matter usually exceeds WHO standards.

Objective:

To assess the influence of air pollution caused by particulate matter on children’s hospitalizations due to respiratory diseases between 2001 and 2005 in the Metropolitan Region of Chile, independently from the environmental presence of respiratory syncytial virus (RSV).

Material and Method:

72,479 public and private hospitalizations due to respiratory diseases of children under 15 years of age residing in the study region were analyzed using a time-stratified alternating case-control design. The main evaluations were: hospitalizations due to respiratory diseases (J00-J99), pneumonia (J12-J18); asthma (J21.0 - J21.9), and bronchiolitis (J45 - J46). Daily compilation of temperature data, PM10, PM2,5, ozone, respiratory virus (RSV), and environmental humidity.

Results:

Mean values of PM10 and PM2.5 were 81.5 and 41.2 pg/m3 respec tively. The average temperature was 12.8 °C and air humidity 72.6%. An increase of 10 pg/m3 of PM25 with one and two days of lag was associated with an hospitalizations increase due to respiratory diseases close to 2%, this percentage increased to 5% when the exposure was with eight days of lag, reflecting synergism between particulate matter and respiratory viruses (RSV).

Conclusion:

Short air pollution exposure can lead to children’s hospitalizations due to respiratory diseases.

Keywords: Air Pollution; Hospitalization; Child; Pneumonia; Bronchiolitis; Asthma; Respiratory Syncytial Virus; Alternate Case-Control Studies

Introduction

Santiago of Chile presents a serious problem of at mospheric pollution due to respirable particulate mat ter in fall and winter, and due to photochemical pollu tion (ozone) in spring and summer months1.

This is due to the geographical and meteorological conditions of the Metropolitan Region atmospheric basin that affect its ventilation capacity and the natural emissions as well as those produced by the daily activi ties of its inhabitants2.

Evidence of the link between particulate matter and damage to public health is consistent and shows its adverse effects to exposures experienced in urban settlements around the world, in both developed and developing countries3,4,5,6,7,8. The range of adverse health effects is wide, affecting both the respiratory and car diovascular systems, where young children and older adults are the most susceptible among the general population9. The risk increases with the exposure inten sity. The threshold existence for such effects is poorly supported. In fact, effects have been described at low levels, not much higher than baseline concentrations estimated at 3 to 5 pg/m3 in the U.S. Epidemiological evidence shows adverse particle effects at short- and long-term exposures10.

The respiratory effects of air pollution have been described mainly for particulate matter and ozone. In the lungs of Fresno inhabitants (Central Valley of California), wall thickening, terminal bronchioles re modeling, collagen increase, interstitial inflammatory cells, and macrophages with particulate matter11 have been reported. These changes were most pronounced in the first generation of the terminal bronchiole, su ggesting that the accumulation of coal and mineral dust in the lung mainly affects the central acinar re gion.

Residence in an area with high levels of particulate matter produces pulmonary retention of large num bers of particles, some of which seems to be combus tion products. This was detected by comparing lungs of Mexico City residents with residents of Vancouver Canada, whose 3-year averages of PM10 (particulate matter < 10 pm aerodynamic diameter) were 66 and 14 pg/m3 respectively12. On the other hand, it has been reported that 96% of the particles detected in lung tis sue from autopsies have a diameter of < 2.5 pm, evi dencing the importance of PM25 as an atmospheric pollutant13.

Exposure to complex mixtures of atmospheric po llutants, mainly particulate matter and ozone, causes structural lung changes induced by chronic inflam mation, causing vascular lung airway remodeling, and repair process alteration. In laboratory animals, expo sure to ozone may increase the toxicity of inhaled par ticles or vice versa14,15. In type II alveolar cells in culture (line A549), urban particulate matter, and particles re leased from diesel and black smoke can be mutagenic by damaging DNA16.

Inflammation is important in the exacerbation of respiratory diseases promoted by exposure to res pirable particulate matter. It has been suggested that physical-chemical reactions occur on the surface of the particles, causing intracellular oxidative stress. Due to the large contact surface between the particles and the pneumocytes, there would be a release of inflam mation mediators in the lung, which would recruit inflammatory cells with an exacerbated response that would generate functional and structural damage that would interfere with pulmonary ventilation.

In the lung damage mechanisms, it has been pro posed that the sequence of events would begin with the activation of the “inflammatory cascade”, which would explain the molecular phenomena that lead to the transcription of pro-inflammatory genes. Respira ble particles would cause oxidative stress in cells, with the generation of lipid peroxidation products such as 4-hydroxynonenal and oxidized glutathione (GSSG). This change in the intracellular redox balance would produce the histone acetylation and the DNA ruptu re, stimulating the mechanisms promotion of genetic transcription. Oxidative stress also directly induces the production of the nuclear factor-kappa B (NF-kappa B), which allows the transcription of pro-inflamma tory genes: tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-8; IL-2, IL-6); granulocyte-macropha ge colony-stimulating factor (GM-CSF), and Inter cellular adhesion molecule-1 (ICAM-1). In addition, oxidative stress and/or direct interaction with particles would stimulate an increase in calcium concentrations (Ca+2), which in turn can stimulate the production of NF-kappa B, with the subsequent greater release of pro-inflammatory substances17.

Immunological mechanisms have also been propo sed that would explain the effects of diesel particulate emissions on asthma. The mechanisms of direct dama ge to the immune system would be an increase in the production of IgE and IgG immunoglobulins, modula tion of cytokine expression with increased interleukins and chemokines levels. Phenomena that would induce the migration of other cell types, mainly eosinophils which are mediators of chronic bronchial inflam mation, prolonged peribronchiolar smooth muscle layer contraction, increased bronchial hypersensitivity, and bronchial mucosa damage, clinically relevant as pects of bronchial asthma18.

Children are a particularly vulnerable group to respiratory problems due to their physical and beha vioral characteristics. At this stage of life, the lung has not reached its full development, there is less colla teral ventilation and the small-airway resistance re presents 50% of the total resistance to airflow19. Most alveoli (80%) develop in the postnatal period. As a result, they have less lung volume and less alveolar surface area, therefore, with the same exposure as adults, a higher dose enters the organism. Airways continue to develop in childhood which implies that the peripheral airway (< 2 mm in diameter) genera tes 50% of the airflow resistance, while in the adult it only corresponds to less than 20%. The absence of collateral ventilation, i.e. pores of Kohn and canals of Lambert, in children, worsen the peripheral airways obstruction. Children breathe more frequently and get more physical exercise than adults, which increa ses the effective dose of air pollutants captured by the lung. In addition, children have less developed respiratory musculature and less coughing effecti veness in cleaning the central airways. The defensi ve mechanisms of the lung are not fully developed, causing greater difficulty in removing particles that reach the airways. Finally, children spend more time outdoors than adults, thus the exposure to air pollu tants is greater. All this makes them more exposed to air pollution than adults20. Therefore, the burden of environmental pollution on the respiratory health of children is greater, especially in developing countries where several other noxae coexist such as indoor air pollution, and malnutrition. Hence the importance of establishing control programs and special atten tion such as the strategies developed in the environ mental pediatrics context.

The hypothesis of this study is that the exposure to respirable particulate matter in Santiago, Chile increa ses the number of hospitalizations due to respiratory disease in children under 15 years of age, regardless of exposure to respiratory viruses.

Therefore, our objective was to determine whether exposure to respirable particulate matter in Santiago of Chile was associated with a higher number of hospita lizations due to respiratory diseases in children under 15 years of age, regardless of the environmental pre sence of respiratory syncytial virus (RSV), during the winter periods of 2001 to 2006.

Material and Method

Study design and statistical analysis

The case-crossover design was used. The control period considered a temporal stratification with ex posures of the same day of the week, month and year respective to the index case, ensuring an unbiased estimation of the conditional logistic regression.

Information on hospitalizations was obtained from the electronic databases of the Department of Statis tics and Health Information (DEIS) of the Ministry of Health, Chile. Information from the Hospital Dischar ge of the Ministry of Health database was extracted from the DEIS website, using a password provided by DEIS to conduct this study.

The DEIS databases are anonymized, i.e. without the names of the persons or their RUT (Chilean ID number), in order to comply with Law 19,628 of 08.18.1999 on the protection of the private life of per sons.

In order to carry out the study, the national hospi tal discharges databases for the study period were filte red to build a new database made up of the discharges of the Metropolitan Region residents, from both the private and public health sectors, under the age of 15, with diagnoses of discharges code ICD-10 J00 - J99. For this purpose, the indicated databases were proces sed with the SPSS software, converted by Stata Transfer to the statistical package STATA version 10 and later combined to the exposure database using the merge command and the date variable.

Study population

Hospitalizations of children in public and private hospitals, residents in the Metropolitan Region of Chi le between 2001 and 2005.

Case definition

Any hospitalization due to respiratory disease of patients under 15 years of age residing in the Metropo litan Region during the fall-winter periods from 2001 to 2005 was considered a case.

Inclusion criteria

Children under 15 years of age, resident in com munes of the Metropolitan Region between March 21, 2001, and September 20, 2005, with a discharge diag nosis of respiratory disease (ICD-10 J00 to J99).

Exclusion criteria

Children hospitalized during the study period in the Metropolitan Region with residence in other com munes of the country and with an inpatient stay longer than seven days since the design studies acute events and considers the case to be its own control.

Study variables

Variable ‘response’

Hospitalizations due to respiratory disease (ICD- 10 codes J00 to J99). The association between conta minants and all respiratory hospitalizations (ICD-10 J00-J99) was explored, in addition to evaluating the association with pneumonia (ICD-10 J12-J18), bron chiolitis (ICD-10 J21.0-J21.9), and asthma (ICD-10 J45-J46).

Exposure to air pollutants assessment

The information came from the Air Quality Moni toring Network (MACAM) which has eight stations for measuring pollutants in the communes of Las Condes, Recoleta, Santiago, La Florida, Pudahuel, El Bosque, Cerrillos, and Cerro Navia. The 24-hour averages of all stations of respirable particulate matter in their PM10 and PM2,5 fractions were used for the fall to winter (March 21 to September 20) months of 2001 to 2005.

The exposure to ozone for the same period of the year was analyzed by means of the 8-hours ozone con centration, using the arithmetic average of the concen tration values of one hour of ozone, corresponding to eight successive hours, between 8 am and 4 pm of the studied days. This exposure indicator was selected be cause it is the time interval with the highest ozone con centration in Santiago and because it coincides with the hours of the population movement and therefore its exposure.

Virus Exposure Assessment

Information on the viral epidemiological situation for the period under study was obtained from the Vi rology Laboratory Surveillance System of the Public Health Institute of Chile, which has in the Metropo litan Region five hospitals and five primary healthca re centers. The detection of respiratory viruses in the exudates of respiratory patients was performed using indirect immunofluorescence (IIF) technique. The number of weekly confirmations of RSV was systema tically recorded.

Covariates

The gender, age, and health insurance regime were analyzed for each of the identified cases.

Statistical Analysis

Descriptive statistics were used with measures of central tendency and dispersion. The correlation de gree between the studied variables was evaluated which allowed showing the sample characteristics and the exposure during the study period.

Inferential statistics were also used to analyze the association between increased particulate matter and hospitalizations due to respiratory diseases in children. In the case-crossover design, conditional logistic regression is used. Results were expressed by estimating the odds ratio (OR) and corresponding 95% confiden ce intervals (STATA 10).

The statistical test to determine the association between disease and exposure, in the case-crossover design, is based only on the discordant pairs. The for mula for estimating the sample size (m) that depends on the number of discordant pairs, to detect a relative risk R is given by:

Ψ corresponds to the odds ratio of the disease expo sure ratio and R to the Relative Risk.

The relative risks considered for the calculation were reported by the study of a cohort of children stu died by Pino et al., in Santiago21, which indicated a 1.09 relative risk, requiring at least a total of 6,657 discor dant pairs. A p-value < 0.05 was considered statistically significant for the association establishment.

The case-crossover design uses conditional logistic regression as a multivariate analysis method. First, the available information was analyzed from a bi-variable perspective, constructing models with hospitalizations due to respiratory disease (Y), for each of the explana tory selected variables (X).

Subsequently, explanatory models of hospitaliza tions due to respiratory disease in children were cons tructed based on the epidemiological history and ob jectives of this thesis, in order to demonstrate or reject the hypothesis.

The general built conditional logistic model result in:

Results

During the study period, 72,479 cases were hospita lized that met the inclusion criteria. It was observed that children younger than one year of age (51.5%), males (56.5%), public healthcare system users (81.91%), and those with pneumonia as discharge diagnosis (29.3%) predominated. About one-third of the cases included in the study stayed only one day hospitalized (Table 1).

Table 1 Characteristics of children hospitalized for respiratory diseases, residents in the Metropolitan Region, 2001-2005 (n = 72479). 

The mean concentrations value of PM10 and PM2.5 was 81.5 and 41.2 pg/m3 respectively. The average tem perature was 12.8 °C and the relative humidity was 72.6 % (Table 2).

Table 2 Atmospheric pollutants and meteorological variables during the study period. 

During the study period, 266 days (38 weeks) were observed out of a total of 920 observed days, which met the criteria of having over 100 detected cases per epi demiological week, giving a prevalence of 28.8% days with exposure to RSV.

Particulate matter PM2.5 maintains its effect by completing the explanatory model with the variables ozone, temperature, and relative humidity, in the absence of RSV (Table 3). When the coarse fraction (PM2,5 - 10 particulate matter between 2.5 and 10 pm) is introduced into the model, the effect of PM2,5 increases slightly with two, eight, and ten days of delay (Table 4). This fraction shows no association with respiratory diseases.

Table 3 Odds Ratio (OR, 95% CI) Respiratory diseases hospitalizations by increments of 10 pg/m3 of MP25 with 1 and 2 days of lag. 

Table 4 Odds Ratio (OR, 95% CI) Respiratory diseases hospitalizations by increments of 10 pg/m3 of MP25 with 8 and 10 days of lag. 

Ozone and temperature behave in a very similar way with a systematic marginal protective effect in all models which are expected results since only fall-win ter periods were evaluated, times in which temperature rises and the presence of very low levels of ozone are not harmful to the population.

The relative humidity on the other hand only be haves marginally protective with lags of one and two days, disappearing its meaning with lags of eight and ten days.

The RSV explains an important part of the model (17 to 27% increase in hospitalizations) and acts syner- gistically with PM2.5 since the hospitalization risk due to PM2.5 increases in the presence of RSV with eight and ten days of delay (Table 5).

Table 5 Explanatory models of hospitalizations, air pollutants and presence of respiratory syncytial virus (RSV). 

There was no significant difference in risk by sex in exposure to particulate matter. The risk increases as the age decreases, however, the risk difference bet ween children younger than five years of age and in fants younger than one year of age was not statistically significant.

Finally, an increase of 10 pg/m3 of PM25 particulate matter explained an increase in hospitalizations due to pneumonia (7.7%), bronchiolitis (11.3%), and asthma (8.5%) for eight days of delay.

Discussion

This study hypothesized that some hospitalizations due to respiratory diseases in children would not have occurred had they not been exposed to air pollution. After adjusting for the ozone presence, temperature, and RSV, it was found that an increase of 10 μg/ m3 of PM2.5 increased hospitalizations due to respiratory diseases by about 2% with one to two days of delay sin ce exposure, and that this percentage increased to 5% of the total hospitalizations due to respiratory diseases in children when exposure occurred with eight days of delay, reflecting the expected synergy between particu late matter and the virus presence in the environment. The found results are within the range described by authors who have studied the effects of Santiago air pollution on their children. Pino et al.21 found an asso ciation between PM25 particulate matter levels of 9.0% in symptomatology exacerbation in asthmatic children with a delay of nine days. Ostro determined that con sultations in Emergency Services increased from 4 to 12% with increases of 50 μg/m3 of PM1022. Ilabaca et al.23 identified a 3.3 % risk of pneumonia in children, all values compatible with the results of this study sin ce the said publications when evaluating ambulatory morbidity, obviously give values higher than those of hospitalizations, since only a fraction of children who consult due to morbidity require hospitalization.

Air quality, during the studied period, presented averages of particulate matter PM10 and PM25 much higher than those suggested by the World Health Organization’s air quality standard and little higher than the primary Chilean air quality standard. Howe ver, the strength of the found association, with respect to the prevailing high pollution situation, was a little lower than the values described in international litera ture. A Canadian study evaluating children aged 2 to 4 years and 5 to 14 years found a risk of emergency services consultation due to asthma of OR 1.08 (1.01 1.16) and OR 1.03 (0.98 -1.07) with a one day delay and an increase in the interquartile range for PM2.5 24. In contrast, another study conducted in a mining in dustrial region of Turkey showed a higher association of asthma with PM2.5 OR 1.25 (1.05-1.50) in children with a delay of four days25. This could indicate that the composition of respirable particulate matter in Santia go would have different toxicity characteristics. Several publications have pointed to the specific components importance of the particulate matter in their toxicity induction mechanisms, which would explain part of the variability in results between cities26,27,28,29,30.

The before mention results may be affected by design limitations. Mainly the exposure assessment carried out on the basis of environmental monitors, which does not allow to identify the true individual exposure and introduces biases in the exposure clas sification. Also, the qualitative characterization of the presence/absence of a virus can affect the results. However, these biases would not present directionality so they should not be affecting the direction of the as sociation, nor do they allow assuming an overestimate of the effect. On the other hand, among the strengths of this study are a) its large number of observations, which makes it possible to show weak associations, b) its capacity to control confusion factor, such as indoor air pollution, smoking, and the socioeconomic condi tion of children exposed to air pollution, and c) the control of variables dependent on variation over time.

Conclusions

The results of this study confirm the harmful effect of atmospheric pollutants, respirable particulate mat ter and ozone, on the respiratory health of children, particularly its effect causing hospitalizations due to pneumonia, bronchiolitis, and asthma.

Regarding the combined effect of the respirable particulate matter presence and environmental virus (RSV), this study supports the thesis of the synergistic effect between the two factors on hospitalizations due to pneumonia, as it reflects that the damage caused by particulate matter increases in the presence of viruses in the environment. The possibility of quantifying the association is very relevant because, although it provi des relatively low values, as the entire population is ex posed, the absolute number of affected people that can be attributed to the phenomenon of pollution, makes it a public health problem.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed ac cording to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regu lations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.

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Received: May 28, 2018; Accepted: November 19, 2018

Correspondence: Patricia Matus c. E-mail: pmatus@uandes.cl.

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