Relationship between household air pollution from biomass smoke exposure, and pulmonary dysfunction, oxidant-antioxidant imbalance and systemic inflammation in rural women and children in Nigeria.

Homo sapiens fine respirable suspended particulate matter

Study subjects

SUBJECT:oluwole-mothers

Rural Nigerian mothers cooking with biomass fuel

type: InVivoSubject Homo sapiens NCBITaxon:9606 sex: female age: 43.0 year (mean; standard deviation ±11.7 year; n=59)

Non-smoking women aged 20-60 years from 59 households in three rural communities (Ajibade, Eruwa, Olorisaoko) near Ibadan, southwest Nigeria, cooking with biomass fuel almost exclusively; nutritionally deficient (pre-albumin and retinol-binding protein below the lower limit of normal).

Cross-sectional pilot study of household air pollution from biomass fuel use; spirometry performed in all 59 mother-child pairs

SUBJECT:oluwole-children

Children of the biomass-exposed rural Nigerian mothers

type: InVivoSubject Homo sapiens NCBITaxon:9606 age: 13.6 year (mean; standard deviation ±3.2 year; n=59)

Children aged 7-17 years living in the same 59 biomass-fuel households as the mothers; the 7-year lower limit was set so that spirometry could be performed reliably. Pre-albumin and retinol-binding protein below the lower limit of normal.

Cross-sectional pilot study of household air pollution from biomass fuel use; spirometry performed in all 59 mother-child pairs

Lung function assays

LF:oluwole-mothers-spirometry

Spirometry - biomass-exposed rural mothers vs ATS-predicted normal

FEV1 in 59 non-smoking rural Nigerian mothers cooking with biomass fuel was significantly lower than the ATS-predicted mean (1.94 +/- 0.51 vs 2.79 +/- 0.36 L/s, p<0.05). FEV1/FVC was also measured and used in the correlation and regression analyses, but Table 1 is not reproduced in the cached full text, so no FEV1/FVC value is recorded here. The comparator record is an external predicted-value reference, not a sampled unexposed household: the authors list the absence of clean-fuel control households as a study limitation. Unit note: the paper prints FEV1 in L/s; FEV1 is a volume, so this is very likely a typo for L in the source, but the unit is recorded as printed (UCUM:L/s) rather than silently normalised.

reference dataset: ATS-recommended predicted normal values

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —
ATS-recommended predicted normal reference values (external reference, not a sampled control group)
COND:oluwole-predicted-normal
— — —

Outputs

GroupOutputDescription
treated Measured FEV1 in biomass-exposed mothers
LF:oluwole-mothers-spirometry-output-exposed · under EXPOSURE:oluwole-hap-biomass
fev1: 1.94 liter per second (mean; standard deviation ±0.51 liter per second; n=59)
control ATS-predicted normal FEV1 for the mothers (external reference values, not a sampled unexposed group)
LF:oluwole-mothers-spirometry-output-predicted · under COND:oluwole-predicted-normal
fev1: 2.79 liter per second (mean; standard deviation ±0.36 liter per second; n=59)

Evidence

Mean FEV1 was significantly lower than mean predicted FEV1 in both mothers (1.94±0.51 vs. 2.79±0.36 L/s, p<0.05)
SUPPORT HUMAN CLINICAL PMID:23777718

States both output values recorded on this assay: the measured mean FEV1 in the exposed mothers and the ATS-predicted mean it was compared with.

Another limitation is the lack of control households where cleaner fuels are used for cooking in the community where the study was performed.
SUPPORT HUMAN CLINICAL PMID:23777718

Justifies modelling the comparator output as an external predicted-value reference rather than as an unexposed control group: the study sampled no clean-fuel households.

LF:oluwole-children-spirometry

Spirometry - biomass-exposed rural children vs ATS-predicted normal

FEV1 in the 59 children of the exposed mothers was significantly lower than the ATS-predicted mean (1.76 +/- 0.54 vs 2.57 +/- 0.66 L/s, p<0.05). The lower age limit of 7 years was set to ensure children could perform spirometry. As with the mothers, the comparator is an external predicted-value reference; the study sampled no clean-fuel control households. Unit note: the paper prints FEV1 in L/s; FEV1 is a volume, so this is very likely a typo for L in the source, but the unit is recorded as printed (UCUM:L/s) rather than silently normalised.

reference dataset: ATS-recommended predicted normal values

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —
ATS-recommended predicted normal reference values (external reference, not a sampled control group)
COND:oluwole-predicted-normal
— — —

Outputs

GroupOutputDescription
treated Measured FEV1 in biomass-exposed children
LF:oluwole-children-spirometry-output-exposed · under EXPOSURE:oluwole-hap-biomass
fev1: 1.76 liter per second (mean; standard deviation ±0.54 liter per second; n=59)
control ATS-predicted normal FEV1 for the children (external reference values, not a sampled unexposed group)
LF:oluwole-children-spirometry-output-predicted · under COND:oluwole-predicted-normal
fev1: 2.57 liter per second (mean; standard deviation ±0.66 liter per second; n=59)

Evidence

and children (1.76±0.54 vs. 2.57±0.66 L/s, p<0.05) (Table 1).
SUPPORT HUMAN CLINICAL PMID:23777718

States both output values recorded on this assay: the measured mean FEV1 in the exposed children and the ATS-predicted mean it was compared with.

Oxidative stress assays

OX:oluwole-mda-mothers

Serum malondialdehyde - biomass-exposed rural mothers

Serum lipid peroxidation measured as MDA by the thiobarbituric acid colorimetric reaction. Mean serum MDA in the exposed mothers was 5.90 +/- 2.40 umol/L, higher than the laboratory normal range of <4.5 umol/L (p<0.05). 55 of the 59 mother-child pairs consented to blood draw, so n = 55. MDA was negatively associated with FEV1/FVC (r=-0.3, p=0.05) but showed no significant correlation with CRP in mothers (r=0.1, p=0.64), and no significant association with measured PM2.5 level.

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum MDA in biomass-exposed mothers
OX:oluwole-mda-mothers-output-exposed · under EXPOSURE:oluwole-hap-biomass
malondialdehyde level: 5.90 micromolar (mean; standard deviation ±2.40 micromolar; n=55)

Evidence

Mean serum MDA concentrations in mothers (5.90±2.40 µmol/L)
SUPPORT HUMAN CLINICAL PMID:23777718

States the mean and standard deviation of serum MDA recorded as this assay's malondialdehyde_level output for the exposed mothers.

OX:oluwole-mda-children

Serum malondialdehyde - biomass-exposed rural children

Serum MDA in the exposed children was 5.44 +/- 1.88 umol/L, higher than the laboratory normal range of <4.5 umol/L (p<0.05), n = 55. In children MDA was positively correlated with CRP (r=0.3, p<0.05) and negatively associated with FEV1/FVC (r=-0.3, p=0.05). No significant association with measured PM2.5 level was observed.

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum MDA in biomass-exposed children
OX:oluwole-mda-children-output-exposed · under EXPOSURE:oluwole-hap-biomass
malondialdehyde level: 5.44 micromolar (mean; standard deviation ±1.88 micromolar; n=55)

Evidence

children (5.44±1.88 µmol/L) were also higher than normal range (<4.5 µmol/L, p<0.05 for both).
SUPPORT HUMAN CLINICAL PMID:23777718

States the mean, standard deviation and normal-range comparison for serum MDA recorded as this assay's malondialdehyde_level output for the exposed children.

OX:oluwole-sod-mothers

Serum superoxide dismutase status - biomass-exposed rural mothers

Serum SOD activity assayed by epinephrine autoxidation inhibition. SOD in the exposed mothers was below the lower limit of the normal range, with 42% of mothers falling below that limit. The paper reports this proportion in the text but gives the mean SOD activity only in Table 2, which is not reproduced in the cached full text, so no numeric superoxide_dismutase_activity value is recorded here. Vitamin C and vitamin E, measured in the same samples, were within their normal ranges. SOD showed a positive correlation with CRP in mothers.

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum SOD status in biomass-exposed mothers
OX:oluwole-sod-mothers-output-exposed · under EXPOSURE:oluwole-hap-biomass
antioxidant enzyme activities: Superoxide dismutase (SOD) below the lower limit of the normal range; 42% of mothers fell below that limit. Vitamin C and vitamin E were within their normal ranges.

Evidence

In the present study, SOD levels in both mothers and children were below the lower limit of normal range with 42% of mothers and 51% of children falling below this limit (Table 2).
SUPPORT HUMAN CLINICAL PMID:23777718

States the depleted antioxidant enzyme status recorded on this assay, including the 42% of mothers below the lower limit of normal.

Our result also showed generation of oxidative stress as SOD showed positive correlation with CRP in mothers and also appeared to be a strong predictor of lung function in children (Table 3).
SUPPORT HUMAN CLINICAL PMID:23777718

Supports this assay's description claim that SOD correlated positively with CRP in the mothers, putting that claim on the same quoted footing as the rest of the file.

OX:oluwole-sod-children

Serum superoxide dismutase status - biomass-exposed rural children

Serum SOD activity assayed by epinephrine autoxidation inhibition. SOD in the exposed children was below the lower limit of the normal range, with 51% of children falling below that limit. As for the mothers, the mean SOD activity appears only in Table 2, which is not in the cached full text, so no numeric superoxide_dismutase_activity value is recorded here. Vitamin C and vitamin E were within their normal ranges. In the regression analysis SOD was a strong predictor of impaired lung function in children (-5.96 +/- 3.05, p=0.05).

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum SOD status in biomass-exposed children
OX:oluwole-sod-children-output-exposed · under EXPOSURE:oluwole-hap-biomass
antioxidant enzyme activities: Superoxide dismutase (SOD) below the lower limit of the normal range; 51% of children fell below that limit. Vitamin C and vitamin E were within their normal ranges.

Evidence

In the present study, SOD levels in both mothers and children were below the lower limit of normal range with 42% of mothers and 51% of children falling below this limit (Table 2).
SUPPORT HUMAN CLINICAL PMID:23777718

States the depleted antioxidant enzyme status recorded on this assay, including the 51% of children below the lower limit of normal.

Regression analysis indicates that serum CRP and SOD concentration levels were strong predictors of impaired lung function in mothers and children, respectively.
SUPPORT HUMAN CLINICAL PMID:23777718

Supports the regression result noted in this assay's description: SOD was the predictor of impaired lung function in the children, CRP in the mothers.

Gene expression assays

GE:oluwole-crp-mothers

Serum C-reactive protein (ELISA) - biomass-exposed rural mothers

Serum CRP in the exposed mothers was 3.79 +/- 1.89 ug/ml, above the laboratory normal range of 1-3 ug/ml, but the difference from the normal range was not statistically significant in mothers (p=0.39). In the regression analysis CRP was a strong predictor of impaired lung function in mothers (-2.55 +/- 1.08, p<0.05). SOD showed a positive correlation with CRP in mothers.

gene expression method: ELISA

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum CRP in biomass-exposed mothers
GE:oluwole-crp-mothers-output-exposed · under EXPOSURE:oluwole-hap-biomass
protein level: 3.79 microgram per milliliter (mean; standard deviation ±1.89 microgram per milliliter; n=55)

Evidence

Additionally, mean serum CRP concentrations in mothers (3.79±1.89 µg/ml) and children (3.56±1.54 µg/ml) were higher than normal range (1-3 µg/ml, p=0.39 and p<0.05, respectively).
SUPPORT HUMAN CLINICAL PMID:23777718

States the mean and standard deviation of serum CRP recorded as this assay's protein_level output for the exposed mothers. Quoted whole so that 'respectively' keeps its referents: the p=0.39 belongs to the mothers and the p<0.05 to the children, so the mothers' elevation above the normal range was NOT statistically significant.

Nearly all mothers and children in our study showed evidence of inflammation, as indicated by elevated CRP levels.
SUPPORT HUMAN CLINICAL PMID:23777718

Attaches the authors' own reading of the CRP results to this assay, so that the link to the systemic-inflammation key event is not carried by the mothers' non-significant p=0.39 alone.

GE:oluwole-crp-children

Serum C-reactive protein (ELISA) - biomass-exposed rural children

Serum CRP in the exposed children was 3.56 +/- 1.54 ug/ml, significantly above the laboratory normal range of 1-3 ug/ml (p<0.05). In children CRP was positively correlated with serum MDA (r=0.3, p<0.05). The authors note that nearly all mothers and children showed evidence of inflammation as indicated by elevated CRP levels, and that nutritional deficiency or unrecognised lung infection could also explain the elevation.

gene expression method: ELISA

Exposure conditions

ConditionAgentConcentrationDuration
Household air pollution from biomass (firewood) smoke during cooking
EXPOSURE:oluwole-hap-biomass
fine respirable suspended particulate matter
ENVO:01000415
1575.1 microgram per cubic meter (median; interquartile range 943.6 to 2847.0 microgram per cubic meter; n=59) —

Outputs

GroupOutputDescription
treated Serum CRP in biomass-exposed children
GE:oluwole-crp-children-output-exposed · under EXPOSURE:oluwole-hap-biomass
protein level: 3.56 microgram per milliliter (mean; standard deviation ±1.54 microgram per milliliter; n=55)

Evidence

Additionally, mean serum CRP concentrations in mothers (3.79±1.89 µg/ml) and children (3.56±1.54 µg/ml) were higher than normal range (1-3 µg/ml, p=0.39 and p<0.05, respectively).
SUPPORT HUMAN CLINICAL PMID:23777718

States the mean, standard deviation and normal-range comparison for serum CRP recorded as this assay's protein_level output for the exposed children. Quoted whole so that 'respectively' keeps its referents: the children's p-value is the p<0.05, so the children's elevation above the normal range was the statistically significant one.

Response comparisons

COMP:oluwole-mothers-fev1

FEV1 in biomass-exposed mothers vs ATS-predicted normal

The paper reports 1.94+/-0.51 vs 2.79+/-0.36 L/s with p<0.05 (a significance threshold, not an exact p-value) and gives no difference, percent change or fold change, so change_value is omitted rather than computed. The comparator is an external predicted-value reference, not a sampled unexposed group.

measurement: fev1 direction: decreased type: absolute difference derivation: reported in paper from assay: LF:oluwole-mothers-spirometry

Statistical test: Student's t-test

COMP:oluwole-children-fev1

FEV1 in biomass-exposed children vs ATS-predicted normal

The paper reports 1.76+/-0.54 vs 2.57+/-0.66 L/s with p<0.05 (a significance threshold, not an exact p-value) and gives no difference, percent change or fold change, so change_value is omitted rather than computed. The comparator is an external predicted-value reference, not a sampled unexposed group.

measurement: fev1 direction: decreased type: absolute difference derivation: reported in paper from assay: LF:oluwole-children-spirometry

Statistical test: Student's t-test

Key-event relationships

KER:oluwole-oxidative-stress-to-lung-function

Increased oxidative stress is associated with decreased lung function

Serum MDA, a marker of systemic lipid peroxidation, was negatively associated with FEV1/FVC in both mothers and children (both r=-0.3, p=0.05). This is a cross-sectional correlation in a cohort with no clean-fuel comparison arm; the paper does not establish direction or causality.

However, MDA concentration was negatively associated with FEV1/FVC in mothers and children (both r=-0.3, p=0.05; Figure 1).
SUPPORT HUMAN CLINICAL PMID:23777718

Reports the negative association between the lipid-peroxidation marker and lung function that this relationship records, as a correlation coefficient rather than a causal effect.

Correlation analysis showed no significant association between PM2.5 concentration levels and serum oxidant parameters.
SUPPORT HUMAN CLINICAL PMID:23777718

Supports the weak evidence_support and the non-causal relationship_type: the measured exposure level itself did not track with the oxidant markers, so no exposure-response claim is made.

KER:oluwole-oxidative-stress-to-systemic-inflammation

Increased oxidative stress is associated with increased systemic inflammation

Serum MDA correlated positively with serum CRP in children (r=0.3, p<0.05) but not in mothers (r=0.1, p=0.64). The association is therefore present in only one of the two groups studied, and the authors note that nutritional deficiency or unrecognised lung infection could also account for the elevated CRP and MDA. Note also the asymmetry on the downstream side: the children's CRP elevation above the normal range was significant (p<0.05) while the mothers' was not (p=0.39), so the systemic-inflammation key event is better supported in the children than in the mothers.

MDA showed a significant positive correlation with CRP only in children (r=0.3, p<0.05) but no significant association was observed in mothers (r=0.1, p=0.64; Figure 2).
SUPPORT HUMAN CLINICAL PMID:23777718

Reports the MDA-CRP correlation behind this relationship and, by showing it in children only, supports recording the evidence as weak rather than consistent across the cohort.

Protocols

PROTOCOL:oluwole-spirometry-001

KoKo spirometry per ATS recommendations

type: SpirometryProtocol

Pulmonary function tests with the PC-based full function KoKo spirometer (nSpire Health, Inc. Longmont, Colorado) in accordance with American Thoracic Society (ATS) recommendations. Spirometry performed at similar times of day to minimise diurnal variation; spirometer calibrated daily and operated within the ambient temperature. FVC, FEV1, FEV1/FVC ratio and peak expiratory flow rate (PEFR) measured. Predicted normal values taken from the ATS recommendations.

spirometry standard: American Thoracic Society (ATS) recommendations

Equipment: KoKo PC-based full function spirometer (nSpire Health, Inc. Longmont, Colorado)

PROTOCOL:oluwole-pm25-001

Real-time indoor PM2.5 monitoring in cooking areas

Indoor air sampling in 59 households. Real-time PM2.5 measured in cooking areas before and during cooking with the pDR 1500 personal aerosol monitor and data logger (Thermo Scientific, Franklin, Massachusetts), using gravimetric and optically-based methods. After calibration and equilibration the instrument cycled every minute for one hour during cooking of evening meals. Sampler placed at the centre of the kitchen, approximately 0.5 m from the ground and within a 1 m radius of the plume from the pollution source.

Equipment: pDR 1500 personal aerosol monitor and data logger (Thermo Scientific, Franklin, Massachusetts)

PROTOCOL:oluwole-mda-001

Serum malondialdehyde by thiobarbituric acid colorimetry

type: MolecularAssayProtocol

Serum lipid peroxidation assayed by the colorimetric reaction between MDA and thiobarbituric acid (Kamal et al., 1989). Venous blood collected in 10 ml Vacutainer EDTA tubes; serum frozen and stored at -80 C until analysis at the Institute for Advanced Medical Research and Training laboratory, University College Hospital, Ibadan.

detection method: colorimetry (MDA-thiobarbituric acid reaction)
PROTOCOL:oluwole-sod-001

Serum superoxide dismutase by epinephrine autoxidation inhibition

type: MolecularAssayProtocol

Antioxidant enzyme superoxide dismutase (SOD) assayed by the epinephrine autoxidation inhibition method (Magwere, Naik, & Hasler, 1997). Vitamin C determined by colorimetric method and vitamin E by high-performance liquid chromatography in the same serum samples.

detection method: epinephrine autoxidation inhibition assay
PROTOCOL:oluwole-crp-elisa-001

Serum C-reactive protein by ELISA

type: MolecularAssayProtocol

Serum C-reactive protein (CRP) levels determined by enzyme-linked immunosorbent assay (ELISA) immunoplate as described by the manufacturer (Immuno-Biological Labs. Inc.).

detection method: ELISA (Immuno-Biological Labs. Inc. immunoplate)