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Table 1 The epidemiological studies included in the review

From: Potential role of polycyclic aromatic hydrocarbons in air pollution-induced non-malignant respiratory diseases

Study design Population Location Exposure characterization Health end-points Correlation/findings References
Case–control 195 children up to 15 years (98 asthma pediatric patients and 97 healthy controls) Arabic children Serum concentrations: Naphthalene, 4H-cyclopenta[def]phenanthrene, 1,2-benzanthracene, chrysene, benzo(e)acephenanthrylene, pyrene, B[a]P, anthracene, fluorene, phenanthrene, fluoranthrene, benzo(e)pyrene Asthma
(IgE, resistin, GMCSF, IFN-γ, IL-4, IL-5, CXCL8 and IL-10)
Naphthalene, 4H-cyclopenta[def]phenanthrene, 1,2-benzanthracene, chrysene, benzo(e)acephenanthrylene associated with IgE, restin, GMCSF, IFN-γ, IL-4, IL-5, CXCL8 and IL-10 [52]
Case–control 453 kindergarten children (126 asthmatic children and 327 controls) From a cohort recruited in 2010 in Taipei, China Urine concentrations:
1- hydroxy-pyrene and 8-OHdG
Information about asthma
Total IgE
1- hydroxy-pyrene significantly associated with asthma (OR 1.42) and IgE [53]
Case–control 42 asthmatic children
20 healthy controls
Hospital-based study in Lucknow, northern India Blood levels:
naphthalene, acenapthene, phenanthrene, anthracene, fluoranthene, pyrene, benzo (b) fluo., benzo (k) fluo., benzo (a) pyrene, di benz (a,h) anthracene
Blood levels of antioxidants (catalase, superoxide dismutase, malon-dialdehyde, reduced GSH) Blood levels of phenanthrene were significantly higher in asthmatics than in healthy children. Blood GSH level was also associated with asthma [54]
Case–control 507 asthmatic adults
536 matched controls
The asthma cases were recruited during 2010–2012 from a hospital in Wuhan, China Urine concentrations:
1-hydroxynaphthalene (1-OHNAP), 2-OHNAP, 9-hydroxyfluorene (9-OHFLU), 2-OHFLU, 4-hydroxyphenanthrene (4-OHPHE), 9-OHPHE, 3-OHPHE, 1-OHPHE, 2-OHPHE, 1-Hydroxypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene
∑OH-PAHs 12 PAHs metabolites
Increased risk of adult asthma diagnosed by physicians Each 1-unit-increase in natural log-transformed concentrations of 2-hydroxyfluorene (2-OHFLU), 4- hydroxyphenanthrene (4-OHPHE), 1-OHPHE, 2-OHPHE, 1-Hydroxypyrene (1-OHPYR) and ∑OH-PAHs were significantly associated with elevated risk of adult asthma with ORs of 2.04, 2.38, 2.04, 1.26, 2.35 and 1.34, respectively [63]
Panel study 72 children with asthma (7–12 years) Area with heavy industry, Montreal, Canada Personal monitoring of various air pollutants including PAHs. Median personal concentration of total PAHs was 130 µg/m3 Respiratory function (spirometry; FEV1, FVC) A possible small decrease in respiratory function with total concentration of PAHs [62]
Panel study 560 adults of 60 years or older Seoul, Korea Urine concentrations:
1-hydroxy-pyrene
2-naphthol
Lung function tests (spirometry)
Genotyping of CYP1A1
Urinary 1-hydroxy-pyrene levels were inversely associated with FEV1/FVC
Haplotype-based CYP1A1 polymorphism modified the risk
[66]
Panel study 88 adult patients with chronic cough Kanazawa University Hospital, Ishikawa Perfecture, Japan Ambient air monitoring of six PAH compounds including fluoranthene, pyrene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene Diary of cough and symptoms
Spesific IgE
Exhaled NO
Association between ambient PAH and cough occurrence. The non-asthma group had slightly higher OR for cough per 1 ng/m3 PAHs than the asthmatics [69]
Cross-sectional 467 children with and without asthma followed up to 8 years Fresno, CA, USA Used a spatiotemporal model to estimated individual exposure: \(\sum\) PAHs with 4, 5, and 6 rings (PAHs456) Respiratory function (spirometry; FEV1, FEF25-75) Non-asthmatics: \(\sum\) PAHs456 exposure during previous periods (3–12 months) associated with decrease in FEV1
Asthmatics: no association
[60]
Cross-sectional 64 schoolchildren Mexico city, Mexico Urine concentration: Monohydroxy-PAHs Respiratory function (spirometry; FEV1, FVC)
pH of exhaled breath condensate (EBC)
Increase of 2-hydroxy-fluorene was significantly negatively associated with FEV1, FVC and pH of EBC [61]
Cross-sectional 3531 people (non-smoker) from 6 to 79 years A Canadian population Urinary concentrations: 1-/2-hydroxy-napthalene, 2-/3-/9-hydroxy-fluorene and 1-/2-/3-/4-/9-hydroxy-phenanthrene, 1-hydroxy-pyrene
Total 11 PAHs
Respiratory function
(spirometry; FEV1 and FVC)
8 PAH metabolites (2-hydroxy-napthalene, 1-/2-hydroxy-phenanthrene, 2-/ 3-/9-hydroxy-fluorene and 3-/4-hydroxy-phenanthrene) were associated with decrements of FEV1 and FVC [65]
Birth cohort 333 newborns from non-smoking women (aged 18–35) Krakow, Poland Personal monitoring of PAHs inhalation in pregnant women for a 48 h period: ∑ PAHs (benzo(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(g,h,i)perylene, benzo(a)pyrene,chrysene/ iso-chrysene, dibenzo(a,h)-anthracene, indeno(1,2,3-c,d)pyrene, and pyrene) Respiratory symptoms based on interview of the mothers Prenatal PAH exposure associated significantly with occurrence of respiratory outcomes: ear infections, cough, throat infections, observed in infants over the first year of life [42]
Birth cohort 257 newborns from non-smoking women (aged 18–35) Krakow, Poland Personal monitoring of PAHs and PM2.5 inhalation in pregnant women for a 48 h period. In addition indoor and outdoor residential air levels of PAHs (both particle-bound and gaseous) and particle mass were measured Number of wheezing days based on interview of the mothers. The new-borns were followed-up every 3 or 6 months with 12 health visits Prenatal and postnatal exposure to PAHs were associated positively with the severity of wheezing days and recurrent wheezing [43]
Birth cohort 339 newborns from non-smoking women (aged 18–35) Krakow, Poland Personal monitoring of PM2.5 inhalation in pregnant women for a 48 h period. BaP-DNA adducts in umbilical cord blood Incidence rate ratio for the number of wheezing days Prenatal levels of BaP-DNA adducts and prenatal PM2.5 levels associated positively with the number of wheezing days during the first 2 years of life [44]
Birth cohort 439 newborns from non-smoking women (aged 18–35) Krakow, Poland Personal monitoring of PAH inhalation in pregnant women during the second trimester
Barbecued meat consumption
Birth outcomes (birth weight, length, head circumference) Airborne PAH and consumption barbecued meat associated with deficit in birth weight [41]
Birth cohort 195 non-asthmatic children of non-smoking mothers Krakow, Poland Personal air monitoring of PAH inhalation in pregnant women for a 48 h period. Geometric mean of PAH concentrations was 20.1 ng/m3. For each child residential air born PAH indoor (21.3 ng/m3) and outdoor (32.5 ng/m3) monitoring was conducted at age of 3 Respiratory function (spirometry; FVC, FEV05, FEV1, FEF25-75) at age 5–9 Prenatal PAH exposure association with reduction of FEV1, FEF25-75. Also postnatal residential indoor PAH levels were associated with reduced FEV1 and FEF25-75 [48]
Birth cohort 222 children age 5 years living in inner-city New York, USA Urine concentrations: 10 monohydroxy-PAHs detected out of 24 metabolites measured Questionnaires to the mothers: Child’s medical history, respiratory symptoms and health-care utilization
Total and specific IgE
Increased 3- hydroxyfluorene and –phenanthrene associated with higher anti-mouse IgE. Also other PAH metabolites showed association using different analyses
No association between PAH metabolites and respiratory symptoms
[55]
Birth cohort Children from 727 non-smoking, African American or Dominican women, the
ages 18–35, living in inner-city
New York, USA Personal monitoring of 8 non-volatile PAHs and pyrene in air for 48 h during the third trimester of pregnancy
Dust collected from homes at different time points both pre- and post-natal for allergen determination
Allergen specific IgE
Glutathione-S-µ1 (GSTM1) gene polymorphisms
Prenatal exposure to non-volatile PAHs and cockroach allergen were associated with increased risk of allergic sensitization. Children null for GSTM1 mutation most vulnerable [46]
Birth cohort  ~ 700 children living in inner-city New York, USA Personal monitoring of 8 non-volatile carcinogenic PAHs and pyrene in air for 48 h during the third trimester of pregnancy Parental report on asthma symptoms in children prior to age of 5 Methylation sensitive restriction fingerprinting of DNA from umbilical cord white blood cells of some cohort children Maternal ∑ PAH exposure exceeding 2.41 ng/m3 was significantly associated with methylation of a specific DNA sequence (ACSL3) and with the parental report of asthma symptoms in children prior to age 5 [45]
Birth cohort Children from 303 non-smoking women living in inner-city New York, USA Personal monitoring of 8 carcinogenic PAHs in air for 48 h during the third trimester of pregnancy Questions to the mothers: Child’s medical history, respiratory symptoms and health-care utilization Prenatal exposure to PAH and early exposure to environmental tobacco smoke (ETS) was associated with increased respiratory symptoms and probable asthma by age 12 to 24 months [49]
Birth cohort Children from 725 non-smoking healthy women living in inner-city New York, USA Personal air monitoring of 8 non-volatile carcinogenic PAHs and pyrene in air for 48 h during the third trimester of pregnancy
Prenatal and postnatal ETS were defined as the report of any smokers in the home. Plasma cotinine was measured in cord blood and child blood
Questionnaires on doctor diagnosis of asthma, emergency room visits due to breathing problems and use of asthma medications in the past 12 month at ages of 5 and 6 years. Total and specific IgE Combined prenatal PAH and ETS exposure were associated with asthma, but not IgE. Prenatal PAH exposure alone was neither associated with asthma nor IgE at age 5 to 6 years [50]
Birth cohort Children from 354 non-smoking healthy women living in inner-city New York, USA Personal air monitoring of 8 non-volatile carcinogenic PAHs and pyrene in air for 48 h during the third trimester of pregnancy
PAH exposure at 5 to 6 years of age was measured from 2-week residential indoor monitoring
Questionnaires on wheeze in the past 12 months, physician diagnosis of asthma and asthma medication in the past 12 month at ages 5 and 6 years. Emergency room visits due to breathing problems
Total and specific IgE
Repeated high exposure to pyrene was associated with asthma, medication use and emergency room visits. No associations between the levels of the 8 non-volatile carcinogenic PAHs and asthma were observed. Non-atopic children seem more susceptible to respiratory consequences of early pyrene exposure [51]
Birth cohort 455 mothers and their children Lodz district, Poland Urine concentration:
1-hydroxy-pyrene (1-HP)
Interview-based; The children’s health status was assessed at the age of 10–18 months and at 2 years Higher 1-HP in mothers at 20–24 weeks of pregnancy increased the risk of respiratory infections in children during their first year of life. Higher 1-HP in children increased their risk of food allergy [78]
Birth cohort 3378 births in a polluted district
1505 in a control district
Two Czech districts: Teplice with high air pollution and Prachatice with lower exposure Air monitoring of mean PM10, PM2.5 and B[a]P estimation for each mother Pregnancy outcomes from medical records; intrauterine growth retardation, respiratory morbidity up to 10 years of age
DNA adducts, micronuclei and gene expression profiles in cord blood
PM10 and B[a]P exposure in the first month of gestation were associated with intrauterine growth retardation. Increased concentrations of PM2.5 and B[a]P associated with development of bronchitis in preschool children
DNA adducts and micronuclei were elevated in cord blood from births in high polluted area
[40]
Birth cohort with repeated-measures 1133 children born in 1994–1998 followed to 3 or 4.5 years of age Two Czech districts: Teplice with high air pollution and Prachatice with lower exposure Air monitoring of PM2.5 and 12 PAHs (gas and particle phases) Questionnaires and medical records: Respiratory illnesses; bronchitis and total lower respiratory illnesses Rising pollutants concentrations (ambient PAHs and PM2.5) were associated with increased bronchitis rates. Associations were stronger for longer pollutant-averaging periods, and among children > 2 years of age for PAH compared with fine particles [79]
Cohort study 315 children aged 6–11 years with asthma followed from 2000 to 2008 Fresno, CA, USA Ambient pollutant concentrations were collected from a central site and at selected homes. Measurements of PAHs: phenanthrene and the sum of nine selected PAH456, which includes fluoranthene, benz[a]anthracene, chrysene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[ghi]perylene, indeno[1,2,3-cd]pyrene, and dibenz[a,h]anthracene Questionnaires and medical records: Increased wheeze PAH exposure were associated with increased wheeze. The trend for increased wheeze persisted among all PAHs measured [56]
Cohort study 2747 participants (18–80 years) Wuhan, China Urinary concentration:
1-hydroxy-naphthalene;
2-hydroxy-naphthalene;
2-hydroxy-fluorene; 9-hydroxy-fluorene
1-hydroxy-phenanthrene;
2-hydroxy-phenanthrene;
3-hydroxy-phenanthrene;
4-hydroxy-phenanthrene;
9-hydroxy-phenanthrene;
1-hydroxy-pyrene;
6-hydroxy-chrysene; and
3-hydroxy-benzo[a]pyrene
Respiratory function (spirometry; FEV1 and FVC) Total and specific urinary PAH metabolites were associated with reduction of FEV1 and FVC [67]
Cohort study 2739 participants (18–80 years) Wuhan, China Urinary concentrations:
12 mono-hydroxy-PAHs
Questionnaire Respiratory function (spirometry; FEV1 and FVC) Urinary hydroxy-PAHs levels were marginally negatively related to FEV1. Low levels of education affected FEV1/FVC together with high exposure to PAHs [68]
Cross-sectional 137 diesel engine testing workers (male) 127 controls Workers at a diesel engine manufacturing plant in China Airborne concentrations of 16 PAHs from PMs
Urinary concentrations:
6 mono-hydroxy-PAHs
Respiratory function
(spirometry)
Increasing levels of PAH metabolites were associated with decreases in respiratory function [71]
Cohort study 1243 coke-oven workers Coke-oven plant in Wuhan, China Urinary concentrations:
12 mono-hydroxy-PAHs
Respiratory function (spirometry; FEV1 and FVC) Total and specific urinary hydroxy-PAHs were associated with accelerated decline in FEV1/FVC [70]
Cohort study 58,862 asphalt workers (men) employed between 1913 and 1999
36,831 persons in a subcohort never exposed to coal tar
Workers from Denmark, Finland, France, Germany Israel, the Netherlands, Norway Estimation of exposure to bitumen fume, coal tar, B[a]P (marker for 4–6-ring PAHs), diesel exhaust, respirable silica and asbestos Mortality from obstructive lung diseases Estimated cumulative and average exposures to PAH and coal tar were associated with mortality from obstructive lung diseases (72)
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