Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution

Lilian Calderón-Garcidueñas, Renaud Vincent, Antonieta Mora-Tiscareño, Maricela Franco-Lira, Carlos Henríquez-Roldán, Gerardo Barragán-Mejía, Luis Garrido-García, Laura Camacho-Reyes, Gildardo Valencia-Salazar, Rogelio Paredes, Lina Romero, Hector Osnaya, Rafael Villarreal-Calderón, Ricardo Torres-Jardón, Milan J Hazucha, William Reed, Lilian Calderón-Garcidueñas, Renaud Vincent, Antonieta Mora-Tiscareño, Maricela Franco-Lira, Carlos Henríquez-Roldán, Gerardo Barragán-Mejía, Luis Garrido-García, Laura Camacho-Reyes, Gildardo Valencia-Salazar, Rogelio Paredes, Lina Romero, Hector Osnaya, Rafael Villarreal-Calderón, Ricardo Torres-Jardón, Milan J Hazucha, William Reed

Abstract

Background: Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure.

Objectives: The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures.

Methods: We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography.

Results: Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03).

Conclusions: Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

Figures

Figure 1
Figure 1
A scatterplot of plasma ET-1 levels by region. Mean plasma ET-1 levels for Mexico City children as a whole (n = 59), as well as for northeast (NEMC, n = 19) and southwest (SWMC, n = 40) Mexico City children analyzed separately were significantly greater than the mean for control (Polotitlán) children (n = 22). Horizontal bar indicates group means. *p < 0.001.
Figure 2
Figure 2
A scatterplot of MPAP by region. The average MPAP for Mexico City children as a whole (n = 59), as well as for northeast (NEMC, n = 19) and southwest (SWMC, n = 40) Mexico City children analyzed separately were significantly greater than the mean for control (Polotitlán) children (n = 22). Horizontal bar indicates group means. *p < 0.01; #p < 0.05.
Figure 3
Figure 3
A plot of MPAP versus ET-1 levels for Polotitlán, northeast (NEMC), and southwest (SWMC) Mexico City children. MPAPs were significantly correlated with ET-1 levels (r = 0.43, p = 0.0001). A linear regression fit to the data is shown.
Figure 4
Figure 4
Scatterplots of complete blood count data by region. WBC, white blood cell. (A) Mean absolute neutrophil counts were significantly lower in Mexico City children (n = 56) than in control children (Polotitlán, n = 22). Northeast Mexico City children (NEMC, n = 17) had significantly lower neutrophil counts than control children (Polotitlán, n = 22). (B) The mean concentration of lymphocytes as a percentage of white blood cells was significantly higher in northeast Mexico City children (NEMC, n = 17) than in controls. (C) Monocyte concentrations were similar in northeast (NEMC, n = 17) and southwest (SWMC, n = 39) Mexico City and control (Polotitlán, n = 22) children. (D) White blood cell concentrations were not significantly different among Mexico City children (n = 59), Polotitlán children (n = 22), northeast (NEMC, n = 19) and southwest (SWMC, n = 40) Mexico City children. Horizontal bar indicates group means. *p < 0.05.
Figure 5
Figure 5
Estimated cumulative dose of PM2.5 (A), PM10 (B), and O3 (C) for northeast (NEMC) and southwest (SWMC) Mexico City averaged (± SE) over the 1-, 2-, and 7-day periods before measurement of ET-1 levels. The average dose calculations were based on estimates for each participating child. There were significant differences between the regions in the 1-, 2-, and 7-day cumulative PM2.5 dose and in the 2-day and 7-day cumulative O3 dose. *p < 0.05; #p < 0.001.

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