Subject(s)
Coronary Artery Disease , Hyperlipidemias , Hyperlipoproteinemia Type II , Cholesterol, LDL , Coronary Artery Disease/epidemiology , Humans , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/genetics , Lipoprotein(a) , PrevalenceABSTRACT
BACKGROUND AND OBJECTIVE: Particulate matter <10 µm (PM10 ) is well recognized as being an important driver of respiratory health; however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community sampled geogenic PM10 . METHODS: This was achieved by collecting earth material from two regional communities in Western Australia (Kalgoorlie-Boulder and Newman), extracting the PM10 fraction and exposing mice by intranasal instillation to these particles. The physicochemical characteristics of the particles were assessed and lung inflammatory responses were compared to control particles. The primary outcomes were cellular influx and cytokine production in the lungs of the exposed mice. RESULTS: The physical and chemical characteristics of the PM10 from Kalgoorlie and Newman differed with the latter having a higher concentration of Fe and a larger median diameter. Control particles (2.5 µm polystyrene) caused a significant influx of inflammatory cells (neutrophils) with little production of proinflammatory cytokines. In contrast, the geogenic particles induced the production of MIP-2, IL-6 and a significant influx of neutrophils. Qualitatively, the response following exposure to particles from Kalgoorlie and Newman were consistent; however, the magnitude of the response was substantially higher in the mice exposed to particles from Newman. CONCLUSIONS: The unique physicochemical characteristics of geogenic particles induced a proinflammatory response in the lung. These data suggest that particle composition should be considered when setting community standards for PM exposure, particularly in areas exposed to high geogenic particulate loads.
Subject(s)
Air Pollutants , Alveolitis, Extrinsic Allergic/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Cytokines/metabolism , Lung/chemistry , Particulate Matter/pharmacokinetics , Administration, Intranasal , Alveolitis, Extrinsic Allergic/chemically induced , Alveolitis, Extrinsic Allergic/pathology , Animals , Disease Models, Animal , Female , Instillation, Drug , Lung/drug effects , Mice , Mice, Inbred BALB C , Neutrophils/chemistry , Particulate Matter/administration & dosageABSTRACT
In healthy individuals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed "bronchoprotection". The mechanism(s) of DI-induced bronchoprotection is unclear. The forced oscillation technique was used to assess the effect of prior DI on subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed likely mechanisms for the bronchoprotective effects of DI including reduced airway narrowing (from changes in airway resistance) and/or closure (changes in tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in airway narrowing). DI prior to MCh challenge: 1) did not reduce but instead enhanced airway narrowing (p<0.05); 2) increased ventilation heterogeneity (p<0.05); 3) enhanced the subsequent bronchodilatory response to DI (p<0.05); and 4) reduced tissue elastance (p<0.05), suggesting opening of closed airways or alveoli units. Our findings suggest that DI prior to MCh challenge may elicit a series of changes, some of which are beneficial to respiratory function (enhanced bronchodilation), while others place greater load on the system (enhanced bronchoconstriction and ventilation heterogeneity). It is proposed that the relative magnitudes of these opposing physiological and mechanical effects will determine the net effect on respiratory function in health and disease.
