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Table 2 Summary of study design characteristics

From: Controlled human exposure to diesel exhaust: a method for understanding health effects of traffic-related air pollution

Publicationa

Study type

Exposure armsb

Length of exposure session (minutes)

Activity during exposure

Period between exposure sessions

Concurrent or additional exposures

Research group

Koch et al. [24]

Crossover

FA + placebo

DE 300 + placebo

FA + salbutamol

DE 300 + salbutamol

90

60 min rest, followed by 30 min cycling at 50% peak power

1–3 weeks

Inhaled salbutamol

Air Pollution Exposure Laboratory, Vancouver, Canada

Li et al. [25]c

Crossover

DE 300 + allergen

FA + saline

FA + allergen

120

n/a

At least 4 weeks

Allergen

 

Ryu et al. [15]

Wooding et al. [26]

DE 300 + allergen

PDDE + allergen

FA + allergen

FA + saline

4 weeks

 

Rabinovitch et al. [27]

Crossover

DE 300

FA

120

n/a

At least 2 weeks

None

 

Wooding et al. [28]

Crossover

DE 300

FA

120

Cycling on stationary bike twice for 15 min each at 30% VO2

4 weeks

None

 

Giles et al. [29]

Giles et al. [30]

Giles et al. [31]

Giles et al. [32]

Crossover

DE 300 three times

FA three times

30

30 min of either high intensity cycling (60% VO2 peak), low intensity cycling (30% VO2 peak), or rest

1 week

None

 

Curran et al. [33]

Crossover

DE 300

FA

120

Alternating 20 min of cycling on stationary bike (ventilation 15 L/min/m2 BSA) and 40 min of rest

4 weeks

None

 

Mookherjee et al. [34]

Crossover

DE 300

FA

120

n/a

4 weeks

Allergen

 

Clifford et al. [35]

Crossover

DE 300 + allergen

FA + allergen

120

Resting

4 weeks

Allergen

 

Kramer et al. [36]

Biagioni et al. [37]

Carlsten et al. [13]

Hosseini et al. [38]

Crossover

DE 300 + allergen

FA + allergen

120

Alternating 15 min cycling (ventilation 15 L/min/m2 BSA) and 45 min rest

4 weeks

Allergen

 

Cliff et al. [39]

Crossover

DE 300

FA

120

2 bouts of 15 min light cycling (ventilation 15 L/min/m2)

4 weeks

None

 

Rider et al. [40]

Crossover

DE 300 + allergen

FA + allergen

120

n/a

4 weeks

Allergen

 

Zhang et al. [41]

Crossover

DE 300 + allergen

FA + allergen

120

n/a

4 weeks

Allergen

 

Carlsten et al. [42]

Crossover

DE 300 + antioxidant

DE 300 + placebo

FA + placebo

120

Cycling for 15 min every hour at 15 L/min/m2 BSA ventilation, otherwise at rest

At least 2 weeks

N-acetylcysteine pre-treatment

 

Jiang et al. [43]

Crossover

DE 300

FA

120

Alternating light exercise (15 min) and rest (45 min) on bike (ventilation 15 L/min/m2 BSA)

At least 2 weeks

None

 

Yamamoto et al. [44]

Crossover

DE 300 + antioxidant

DE 300 + placebo

FA + placebo

120

15 min cycling per hour (ventilation 15 L/min/m2 BSA), otherwise rest

At least 2 weeks

N-acetylcysteine pre-treatment

 

Giles et al. [45]

Crossover

DE 300

FA

60

Resting

At least 1 week

None

 

Mills et al. [46]

Crossover

DE 300

PDDE

Carbon nanoparticles

FA

120

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 2 weeks

Carbon nanoparticles

Edinburgh University, Edinburgh, UK

Langrish et al. [47]d

Crossover

Mills et al. [46]:

DE 300

PDDE

Carbon nanoparticles

FA

Barath et al. [86]:

DE 250

FA

Cruts et al. [91], Mills et al. [93, 96],:

DE 300

FA

Mills et al. [46]: 120

Barath et al. [86], Cruts et al. [91], Mills et al. [93, 96]: 60

Mills et al. [46, 96]: alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

Barath et al. [86]:

alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

Cruts et al. [91]: resting

Mills et al. [93]: alternating 15 min cycling (ventilation 15 L/min/m2 BSA) and 15 min rest

Mills et al. [46, 93]: at least 2 weeks

Barath et al. [86]: 22–62 days

Cruts et al. [91]: 2–4 days

Mills et al. [96]: 2 weeks

Mills et al. [46]: carbon nanoparticles

Barath et al. [86], Cruts et al. [91], Mills et al. [93, 96]: none

Mills et al. [46]: Edinburgh University, Edinburgh, UK

Barath et al. [86], Cruts et al. [91], Mills et al. [93, 96]:

Umea University, Umea, Sweden

Hussain et al. [48]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

1–3 weeks

None

Environmental and Occupational Health Sciences Institute, New Jersey, USA

Pettit et al. [49]

Crossover

DE 300

FA

60

Resting

At least 1 week

None

 

Kipen et al. [50]

Crossover

n = 26:

DE 200

Secondary organic aerosol

FA

n = 12:

DE 200

FA

120

Resting

At least 1 week

Secondary organic aerosol

 

Laumbach et al. [51]

Crossover

DE 300

FA

60

n/a

At least 1 week

Half of the participants had a stressor task (4 min public speaking or 4 min arthimetic problems)

 

Huyck et al. [52]

Laumbach et al. [53]

Crossover

DE 300

FA

60

Resting

At least 1 week

None

 

Pawlak et al. [54]

Parallel

n = 11:

DE 100

n = 11:

FA

120

n/a

n/a

Live attenuated influenza virus

Environmental Protection Agency Human Studies Facility, Chapel Hill, USA

Stiegel et al. [55]

Madden et al. [56]

Crossover

DE 300

DE 300 + O3

FA

O3

For each arm, participants underwent a session with the listed condition followed by a session of O3 next day

120

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 13 days

O3

 

Tong et al. [57]

Single sequence

DE 100

DE 200

DE 300

120

Resting

At least 2 weeks

None

 

Channell et al. [58]

Lund et al. [59]

Lund et al. [60]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 4 weeks

None

 

Noah et al. [61]

Parallel

n = 9:

allergic rhinitics exposed to DE 100

n = 7:

allergic rhinitics exposed to FA

n = 8:

healthy subjects exposed to DE 100

n = 8:

healthy subjects exposed to FA

120

Resting

n/a

Live attenuated influenza virus

 

Pleil et al. [62]

Hubbard et al. [63]

Sawyer et al. [64]

Sobus et al. [65]

Crossover

DE 100

FA

120

Intermittent cycling at 20 L/min/m2

3 weeks–6 months

None

 

Wauters et al. [66]

Crossover

n = 14:

DE 300 + resting

AA + resting

n = 11:

DE 300 + resting

AA + resting

DE 300 + exercise

AA + exercise

DE + resting and AA + resting: 120

DE + exercise and AA + exercise: 60

n = 14:

resting

n = 11:

resting or exercise (alternating 20 min exercise, 20 min rest, 20 min exercise)

At least 1 week

None

Erasme hospital, Bruxelles, Belgium

Wauters et al. [67]

Crossover

n = 10:

DE 300

AA

n = 8:

DE 300 + exercise in hypoxia

AA + exercise in normoxia

AA + exercise in hypoxia

120

n = 8:

exercise in normoxia

exercise in hypoxia

At least 1 week

n = 10:

dobutamine stress

n = 8:

exercise in hypoxia

 

Wauters et al. [68]

Crossover

n = 7:

DE 300 + resting

AA + resting

n = 5:

DE 300 + resting

AA + resting

DE 300 + exercise

DE + resting and AA + resting: 120

DE + exercise: 60

n = 7:

resting

n = 5:

resting or exercise (two 20 min bouts of exercise at ventilation 20 L/min/m2)

At least 1 week

None

 

Nightingale et al. [69]

Crossover

DEP 200

FA

120

Resting

4 weeks

None

Imperial College School of Medicine, London, UK

Sawant et al. [70]

Crossover

DE 100

FA

FA + NO2

120

Four 15 min bouts of moderate cycling on a stationary bicycle

At least 4 weeks

NO2

Los Amigos Research and Education Institute (LAREI), Downey, USA

Lu et al. [71]e

Crossover

Lund study (Wierzbicka et al. [73]):

DE 300 + 46 dB noise

DE 300 + 75 dB noise

FA + 46 dB noise

FA + 75 dB noise

EPA study (Pleil et al.  [62], Hubbard et al. [63], Sawyer et al. [64], Sobus et al. [65]):

DE 100

FA

Lund study: 180

EPA study: 120

Lund study:

resting

EPA study: intermittent cycling at 20 L/min/m2

Lund study:

at least 1 week

EPA study:

at least 3 weeks

Lund study:

46 dB or 75 dB traffic noise

EPA study:

none

Lund University (Lund, Sweden) and Environmental Protection Agency Human Studies Facility (Chapel Hill, USA)

Hemmingsen et al. [72]

Wierzbicka et al. [73]

Xu et al. [74]

Crossover

DE 300 + 46 dB noise

DE 300 + 75 dB noise

FA + 46 dB noise

FA + 75 dB noise

180

Resting

At least 1 week

46 dB or 75 dB traffic noise

Lund University, Lund, Sweden

Lucking et al. [75]

Crossover

Protocol 1:

DE 350

FA

Protocol 2:

DE 350

FA

protocol 1: 120

protocol 2: 60

Both protocol 1 and 2: alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 1 week

None

Protocol 1: Edinburgh, UK, protocol 2: Umea University (Umea, Sweden)

Gouveia-Figueira et al. [76]

Gouveia-Figueira et al. [77]

Crossover

DE 150

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

Umea University, Umea, Sweden

Behndig et al. [78]f

Crossover

Behndig et al. [83] and Larsson et al. [82]:

DE 100

FA

120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Muala et al. [79]

Crossover

DE 350

PDDE (filter A)

PDDE (filter B)

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 1 week

None

 

Barath et al. [80]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 2 weeks

None

 

Langrish et al. [81]

Crossover

DE 300

FA

n/a

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 1 week

Study 1 (n = 16): NO synthase inhibitor + sodium nitroprusside + acetylcholine

Study 2 (n = 14): NO synthase inhibitor

 

Larsson et al. [82]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Löndahl et al. [22]

Crossover

DE 50 (idling)

DE 300 (transient driving)

33

Resting

Different days

None

 

Rissler et al. [23]

Crossover

DE 50 (idling)

DE 300 (transient driving)

33

Resting

Different days

None

 

Behndig et al. [83]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Lucking et al. [84]

Crossover

DE 300

PDDE

FA

60

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 1 week

None

 

Mills et al. [85]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA for healthy, 15 L/min/m2 for CAD subjects) and 15 min rest

At least 2 weeks

None

 

Barath et al. [86]

Crossover

DE 250

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

22–62 days

None

 

Sehlstedt et al. [87]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Langrish et al. [88]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 1 week

None

 

Lundbäck et al. [89]

Crossover

DE 350

FA

60

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

At least 1 week

None

 

Bosson et al. [90]

Crossover

DE 300 + O3

FA + O3

DE and FA: 60

O3: 120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

3–5 weeks

O3

 

Cruts et al. [91]

Crossover

DE 300

FA

60

Resting

2–4 days

None

 

Bosson et al. [92]

Crossover

DE 300 + O3

DE 300 + FA

DE and FA: 60

O3: 120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

3–6 weeks

O3

 

Mills et al. [93]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 15 L/min/m2 BSA) and 15 min rest

At least 2 weeks

None

 

Törnqvist et al. [94]

Crossover

DE 300

FA

60

Alternating 15 min cycling and 15 min rest

At least 2 weeks

None

 

Behndig et al. [95]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Mills et al. [96]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 25 L/min/m2 BSA) and 15 min rest

2 weeks

None

 

Pourazar et al. [97]

Pourazar et al. [98]

Salvi et al. [99]

Salvi et al. [100]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Mudway et al. [101]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 15–20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Stenfors et al. [102]

Crossover

DE 100

FA

120

Alternating 15 min cycling (ventilation 15–20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Nordenhäll et al. [14]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Nordenhäll et al. [103]

Crossover

DE 300

FA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 2 weeks

None

 

Rudell et al. [104]

Crossover

DE 300

PDDE (filter A)

PDDE (filter B)

PDDE (filter C)

PDDE (filter D)

FA

60

Resting

6 days

None

 

Rudell et al. [105]

Crossover

DE ?

PDDE

AA

60

Alternating 10 min cycling on bike at 75 W (15 L/min/m2 BSA) and 10 min rest

3 weeks

None

 

Blomberg et al. [106]

Crossover

DE 300

AA

60

Alternating 15 min cycling (ventilation 20 L/min/m2 BSA) and 15 min rest

At least 3 weeks

None

 

Rudell et al. [107]

Crossover

DE ?

PDDE

AA

60

Alternating 10 min cycling on bike at 75 W and 10 min rest

n/a

None

 

Rudell et al. [108]

Single arm

DE?

60

Alternating 10 min cycling on bike at 75 W and 10 min rest

n/a

None

 

Tousoulis et al. [109]

Crossover

DE 25

FA

120

n/a

4 weeks

None

University of Athens, Athens, Greece

Vieira et al. [110]

Vieira et al. [111]

Crossover

DE 300

PDDE

FA

21

15 min rest then 6 min walking without inclination, self-paced

At least 48 h

None

University of Sao Paulo Medical School, Sao Paulo, Brazil

Cosselman et al. [112]

Crossover

DE 200 + placebo

FA + placebo

DE 200 + antioxidant

FA + antioxidant

120

n/a

At least 2 weeks

Ascorbate and N-acetylcysteine pre-treatment

University of Washington, Seattle, USA

Sack et al. [16]

Crossover

DE 200 + antioxidant

DE 200 + placebo

FA + antioxidant

FA + placebo

120

n/a

At least 3 weeks

Ascorbate and N-acetylcysteine pre-treatment

 

Carlsten et al. [113]

Crossover

Experiments 1 and 2:

DE 100

DE 200

FA

Experiment 3:

DE 200 + antioxidant

DE 200 + placebo

FA + antioxidant

FA + placebo

120

Resting

2–4 weeks

Experiments 1 and 2: none

Experiment 3: antioxidant

 

Krishnan et al. [114]

Crossover

DE 200

FA

120

Resting

2 weeks

None

 

Cosselman et al. [115]

Crossover

DE 200

FA

120

Resting

At least 2 weeks

None

 

Allen et al. [116]

Crossover

DE 200

FA

120

n/a

n/a

None

 

Carlsten et al. [117]

Crossover

DE 100

DE 200

FA

120

Resting

At least 2 weeks

None

 

Peretz et al. [118]

Crossover

DE 100

DE 200

FA

120

Resting

At least 2 weeks

None

 

Peretz et al. [119]

Crossover

DE 100

DE 200

FA

120

Resting

At least 2 weeks

None

 

Carlsten et al. [120]

Crossover

DE 100

DE 200

FA

120

Resting

Exposures on 3 different days

None

 

Peretz et al. [121]

Crossover

DE 50

DE 100

DE 200

FA

120

Resting

At least 2 weeks

None

 
  1. AA ambient air, BSA body surface area, CAD coronary artery disease, DE diesel exhaust, DE 50 diesel exhaust at a target (or achieved concentration, if target concentration was not specified) concentration of 50 μg/m3and so on, DEP diesel exhaust particles, DEP 200 diesel exhaust particles at a target concentration of 200 μg/m3, FA filtered air, FiO2 fraction of inspired oxygen, min minute, NO nitric oxide, NO2 nitrogen dioxide, O2 oxygen, O3 ozone, PDDE particle depleted diesel exhaust, VO2 maximal oxygen uptake
  2. aPublications listed in order of research group alphabetically, then by most recent year of publication, then alphabetically by author name. Publications that used the same cohort of participants (or subset of participants from the same cohort) and same exposure arms have been grouped together
  3. bUnless otherwise specified (e.g., parallel design), participants were exposed once to each exposure arm listed
  4. cLi et al. [25] is derived from the same study as Ryu et al. [15] and Wooding et al. [26], but only uses a subset of the study arms
  5. dLangrish et al. [47] uses data pooled from multiple publications, including Barath et al. [86], Cruts et al. [91], Mills et al. [46, 93, 96]. Only data pertaining to DE exposures were considered in this review
  6. eSpecimens used in Lu et al. [71] were derived from participants in Pleil et al. [62] (EPA study), Hubbard et al. [63] (EPA study), Sawyer et al. [64] (EPA study), Sobus et al. [65] (EPA study), and Wierzbicka et al. [73] (Lund study)
  7. fBehndig et al. [78] uses archived biopsies from Behndig et al. [83] and Larsson et al. [82]