particulates, ROS, and other mechanisms: BBB & CNS

[Guest guest]

Although air pollution, ozone, and particulates are often studied in

relation to asthma and lung function (eg, 1-3) and supplements (eg, 4),

particulates also affect and cross the BBB (5). Given that some

antioxidants may counter oxidative stress, I can't help but wonder what

supplements (if any) would augment detoxification and elimination of

particulate matter and its subparticles (see 5) before they reach the

BBB & CNS. Alternatively, are most of us to enjoy supplement-augmented

lung function and reduced levels of ROS while nonetheless experiencing

ongoing BBB & CNS effects (5) from small and ultrafine particulate

matter our bodies didn't detoxify?

*//*

1. Low levels of air pollution induce changes of lung function in a

panel of schoolchildren. <http://www.ncbi.nlm.nih.gov/pubmed/16455832>

Moshammer H, Hutter HP, Hauck H, Neuberger M.

Eur Respir J. 2006 Jun;27(6):1138-43.

pdf: http://erj.ersjournals.com/content/27/6/1138.long

In search of sensitive screening parameters for assessing acute effects

of ambient air pollutants in young schoolchildren, the impact of 8-h

average air pollution before lung function testing was investigated by

oscillatory measurements of resistance and spirometry with flow-volume

loops. At a central elementary school in Linz, the capital of Upper

Austria, 163 children aged 7-10 yrs underwent repeated examinations at

the same time of day during 1 school year, yielding a total of 11-12

lung function tests per child. Associations to mass concentrations of

particulate matter and nitrogen dioxide (NO(2)) measured continuously at

a nearby monitoring station were tested, applying the Generalised

Estimating Equations model. Reductions per 10 microg.m(-3) (both for

particles and for NO(2)) were in the magnitude of 1% for most lung

function parameters. The most sensitive indicator for acute effects of

combustion-related pollutants was a change in maximal expiratory flow in

small airways. NO(2) at concentrations below current standards reduced

(in the multipollutant model) the forced expiratory volume in one second

by 1.01%, maximal instantaneous forced flow when 50% of the forced vital

capacity remains to be exhaled (MEF(50%)) by 1.99% and MEF(25%) by

1.96%. Peripheral resistance increased by 1.03% per 10 microg.m(-3) of

particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mum

(PM(2.5)). Resistance is less influenced by the child's cooperation and

should be utilised more often in environmental epidemiology when

screening for early signs of small airway dysfunction from urban air

pollution, but cannot replace the measurement of MEF(50%) and MEF(25%).

In the basic model, the reduction of these parameters per 10

microg.m(-3) was highest for NO(2), followed by PM(1), PM(2.5) and

PM(10), while exposure to coarse dust (PM(10)-PM(2.5)) did not change

end-expiratory flow significantly. All acute effects of urban air

pollution found on the lung function of healthy pupils were evident at

levels below current European limit values for nitrogen dioxide. Thus,

planned reduction of nitrogen dioxide emission (Euro 5; vehicles that

comply with the emission limits as defined in Directive 99/96/EC) of 20%

in 2010 would seem to be insufficient.

2. Personal and ambient air pollution exposures and lung function

decrements in children with asthma.

<http://www.ncbi.nlm.nih.gov/pubmed/18414642>

Delfino RJ, Staimer N, Tjoa T, Gillen D, Kleinman MT, Sioutas C, D.

Environ Health Perspect. 2008 Apr;116(4):550-8.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291010/?tool=pubmed

BACKGROUND: Epidemiologic studies have shown associations between asthma

outcomes and outdoor air pollutants such as nitrogen dioxide and

particulate matter mass < 2.5 microm in diameter (PM(2.5)). Independent

effects of specific pollutants have been difficult to detect because

most studies have relied on highly correlated central-site measurements.

OBJECTIVES: This study was designed to evaluate the relationship of

daily changes in percent-predicted forced expiratory volume in 1 sec

(FEV(1)) with personal and ambient air pollutant exposures.

METHODS: For 10 days each, we followed 53 subjects with asthma who were

9-18 years of age and living in the Los Angeles, California, air basin.

Subjects self-administered home spirometry in themorning, afternoon, and

evening. We measured personal hourly PM(2.5) mass, 24-hr PM(2.5)

elemental and organic carbon (EC-OC), and 24-hr NO(2), and the same

24-hr average outdoor central-site(ambient) exposures. We analyzed data

with transitional mixed models controlling for personal temperature and

humidity, and as-needed beta(2)-agonist inhaler use.

RESULTS: FEV(1) decrements were significantly associated with increasing

hourly peak and daily average personal PM(2.5), but not ambient PM(2.5).

Personal NO(2) was also inversely associated with FEV(1). Ambient NO(2)

was more weakly associated. We found stronger associations among 37

subjects not taking controller bronchodilators as follows: Personal

EC-OC was inversely associated with morning FEV(1); for an interquartile

increase of 71 microg/m(3) 1-hr maximum personal PM(2.5), overall

percent-predicted FEV(1) decreased by 1.32% [95% confidence interval

(CI), -2.00 to -0.65%]; and for an interquartile increase of 16.8 ppb

2-day average personal NO(2), overall percent-predicted FEV(1) decreased

by 2.45% (95% CI, -3.57 to -1.33%). Associations of both personal

PM(2.5) and NO(2) with FEV(1) remained when co-regressed, and both

confounded ambient NO(2).

CONCLUSIONS: Independent pollutant associations with lung function might

be missed using ambient data alone. Different sets of causal components

are suggested by independence of FEV(1) associations with personal

PM(2.5) mass from associations with personal NO(2).

3. Effects of ozone and other pollutants on the pulmonary function of

adult hikers. <http://www.ncbi.nlm.nih.gov/pubmed/9435151>

Korrick SA, Neas LM, Dockery DW, Gold DR, GA, Hill LB, Kimball KD,

Rosner BA, Speizer FE.

Environ Health Perspect. 1998 Feb;106(2):93-9.

pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533017/?tool=pubmed

This study evaluated the acute effects of ambient ozone (O3), fine

particulate matter (PM2.5), and strong aerosol acidity on the pulmonary

function of exercising adults. During the summers of 1991 and 1992,

volunteers (18-64 years of age) were solicited from hikers on Mt.

Washington, New Hampshire. Volunteer nonsmokers with complete covariates

(n = 530) had pulmonary function measured before and after their hikes.

We calculated each hiker's posthike percentage change in forced

expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), the

ratio of these two (FEV1/FVC), forced expiratory flow between 25 and 75%

of FVC(FEF25-75%), and peak expiratory flow rate (PEFR). Average O3

exposures ranged from 21 to 74 ppb. After adjustment for age,sex,

smoking status (former versus never), history of asthma or wheeze, hours

hiked, ambient temperature, and other covariates, there was a 2.6%

decline in FEV1 [95% confidence interval (CI), 0.4-4.7; p = 0.02] and a

2.2% decline in FVC (CI, 0.8-3.5; p =0.003) for each 50 ppb increment in

mean O3. There were consistent associations of decrements in both FVC

(0.4% decline; CI,0.2-0.6, p = 0.001) and PEFR (0.8% decline; CI,

0.01-1.6; p = 0.05) with PM2.5 and of decrements in PEFR (0.4% decline;

CI, 0.1-0.7; p = 0.02) with strong aerosol acidity across the

interquartile range of these exposures. Hikers with asthma or a history

of wheeze (n = 40) had fourfold greater responsiveness to ozone than

others. With prolonged outdoor exercise, low-level exposures to O3,

PM2.5, and strong aerosol acidity were associated with significant

effects on pulmonary function among adults. Hikers with a history of

asthma or wheeze had significantly greater air pollution-related changes

in pulmonary function.

4. Diet and obstructive lung diseases.

<http://www.ncbi.nlm.nih.gov/pubmed/12192737>

Romieu I, Trenga C.

Epidemiol Rev. 2001;23(2):268-87.

pdf: http://epirev.oxfordjournals.org/content/23/2/268.long

The results presented in this review suggest that the impact of

nutrition on obstructive lung disease is most evident for antioxidant

vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By

decreasing oxidant insults to the lung, antioxidants could modulate the

development of chronic lung diseases and lung function decrement.

Antioxidant vitamins could also play an important role in

gene-environment interactions in complex lung diseases such as childhood

asthma. Data also suggest that omega-3 fatty acids may have a

potentially protective effect against airway hyperreactivity and lung

function decrements; however, relevant data are still sparse. Although

epidemiologic data suggest that consumption of fresh fruit may reduce

risk of noncarcinogenic airway limitation, there are no clear data on

which nutrients might be most relevant. While some studies evaluate

daily intake of vitamin C, other studies use fruit consumption as a

surrogate for antioxidant intake. Given the dietary intercorrelations

among antioxidant vitamins, particularly vitamin C, beta-carotene, and

flavonoids, as well as other micronutrients, it may be difficult to

isolate a specific effect. Some population subgroups with higher levels

of oxidative stress, such as cigarette smokers, may be more likely to

benefit from dietary supplementation, since some studies have suggested

that antioxidant intake may have a greater impact in this group. Studies

of lung function decrement and COPD in adults suggest that daily intake

of vitamin C at levels slightly exceeding the current Recommended

Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among

smokers) may have a protective effect (20). In the Schwartz and Weiss

(85) and Britton et al. (87) studies, an increase of 40 mg/day in

vitamin C intake led to an approximate 20-ml increase in FEV1. Daily

mean vitamin C intakes in these studies were 66 mg and 99.2 mg,

respectively, and the highest intake level (178 mg/day) was

approximately three times the Recommended Dietary Allowance. Although

the amplitude of the effect was modest, if these effects accumulate over

20-30 years, they could have a meaningful impact on the rate at which

pulmonary function declines, particularly in symptomatic subjects (85).

Longitudinal data support the hypothesis that fresh fruit consumption

has a beneficial impact on the lung (95). Among children, consumption of

fresh fruit, particularly fruit high in vitamin C, has been related to a

lower prevalence of asthma symptoms and higher lung function (64). This

effect was observed event at low levels of fruit consumption (one or two

servings per week vs. less than one serving per week), which suggests

that a small increase in dietary intake could have a beneficial effect.

Consumption of fish has also been related to lower airway

hyperreactivity among children (75) and higher lung function in adults

(100); however, longitudinal data do not provide evidence that increased

omega-3 fatty acid intake protects against lung disease (101).

Experimental studies of persons with asthma suggest that magnesium

infusion may have a place in the acute treatment of asthma, but it does

not seem to have long-term benefits. The studies of sodium, selenium,

and fish oils do not show convincing evidence of clinical benefits.

Studies of vitamin C supplementation suggest a short-term protective

effect on airway responsiveness and pulmonary function. It remains to be

proven whether consistent use of vitamin C would have a protective

effect on the evolution of chronic asthma. Results from supplementation

studies conducted among subjects exposed to high levels of oxidants

(57-60) suggest that daily intake of antioxidant vitamins exceeding the

Recommended Dietary Allowance may have a beneficial effect on lung

airways and that intake higher than the Recommended Dietary Allowance

should be recommended for populations chronically exposed to

photooxidant air pollutants (such as ozone), cigarette smoking, or

vigorous exercise. It is difficult to determine the amounts of

antioxidant vitamins that people should consume. In particular, although

vitamin C was shown to have maximum bioavailability when given in a

single dose of 200 mg (102), experiments on which this finding was based

were conducted under normal conditions. Guidelines from the US National

Cancer Institute (103) recommend consumption of five servings of fruit

and vegetables daily, corresponding to a vitamin C intake exceeding 200

mg. Dietary surveys carried out in the US population indicate that less

than 12 percent of US children and adults meet this recommended level of

intake (104). Diet appears to be an important cofactor in the

development of obstructive lung disease, although data are still sparse.

There is a need for further research in experimental and epidemiologic

settings to better understand the physiologic effects of antioxidant

vitamins, omega-3 fatty acids, and other nutrients on lung tissues. The

impact of diet on the incidence and evolution of asthma and COPD should

be investigated using a cohort design that accounts for known risk

factors. This will allow researchers to evaluate the exposure-disease

relation over an adequate time frame and obtain insight into the

causality of the relation. Some of these studies should enroll infants

and young children to determine the impact of early diet on respiratory

health. Research should also focus on the equally challenging policy

issues--namely, finding effective methods of convincing people to

increase their daily consumption of fresh fruits and vegetables, to stop

smoking cigarettes, and to minimize their environmental and occupational

exposure to pollutants and other agents that cause respiratory disease.

5. Excellent review!

Air pollution: mechanisms of neuroinflammation and CNS disease.

<http://www.ncbi.nlm.nih.gov/pubmed/19716187>

Block ML, Calderón-Garcidueñas L.

Trends Neurosci. 2009 Sep;32(9):506-16.

pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743793/?tool=pubmed

Air pollution has been implicated as a chronic source of

neuroinflammation and reactive oxygen species (ROS) that produce

neuropathology and central nervous system (CNS) disease. Stroke

incidence and Alzheimer's and Parkinson's disease pathology are linked

to air pollution. Recent reports reveal that air pollution components

reach the brain; systemic effects that impact lung and cardiovascular

disease also impinge upon CNS health. While mechanisms driving air

pollution-induced CNS pathology are poorly understood, new evidence

suggests that microglial activation and changes in the blood-brain

barrier are key components. Here we summarize recent findings detailing

the mechanisms through which air pollution reaches the brain and

activates the resident innate immune response to become a chronic source

of pro-inflammatory factors and ROS, culminating in CNS disease.