Table 1 The epidemiological studies included in the review

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, FEF_25-75)

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 PM_2.5 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 PM_2.5 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 PM_2.5 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, FEF_25-75) at age 5–9

Prenatal PAH exposure association with reduction of FEV1, FEF_25-75. Also postnatal residential indoor PAH levels were associated with reduced FEV₁ and FEF_25-75

[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, PM_2.5 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 PM_2.5 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 PM_2.5 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 PM_2.5) 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

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