Introduction
Methods
Literature Search
Study Eligibility
Study Outcomes
Data Extraction
Risk of Bias Assessment
Data Synthesis and Meta-analysis
Results
Study Selection
Study Characteristics
Study | Country of origin | N-ERD study no | ATA study no | Controls | Age, N-ERD (ya) | Age, ATA (ya) | Gender, male (%) | Subjects | Definition of asthma | Lung function, FEV1 (%) |
---|---|---|---|---|---|---|---|---|---|---|
Ban et al. 2016 [39] | South Korea | 45 | 44 | N/A | 40.3 (13.4) | 45.6 (13.5) | 32.6% | NS | ATS criteria | N-ERD [mean, SD] = 84.7 (17.9) ATA [mean, SD] = 86.3 (16.2) |
Ban et al. 2021 [49•] | South Korea | 47 | 90 | 20 | 51.8 (11.9) | 49.4 (16.2) | 35.0% | Exclusion: treatment with type 2 biologics within 130 days of enrollment; current smokers or recent ex-smokers; controller medication change within 7 days of enrollment | GINA guidelines | N-ERD [mean, SD] = 90.0 (19.5) ATA [mean, SD] = 90.7 (16.9) |
Bochenek et al. 2003 [25] | Poland | 65 | 66 | 50 | 41.6 (12.4) | 34.6 (12.9) | 38.9% | Stable asthma Exclusion: exacerbation or LRTI in preceding 6 weeks | NS | N-ERD [mean, SD] = 84.9 (14.3) ATA [mean, SD] = 92.5 (14.5) |
Bochenek et al. 2018 [8] | Poland | 247 | 239 | 95 | 49.3 (12.9) | 49.3 (14.8) | 30.9% | Stable asthma Exclusion: exacerbation in preceding 6 weeks | NS | N-ERD [mean, SD] = 80.0 (19.9) ATA [mean, SD] = 87.0 (19.8) |
Cahill et al. 2015 [41] | USA | 29 | 10 | N/A | 47.3 (9.9) | 36.3 (3.3) | 41% | Non-smoker; N-ERD group consisted of subjects undergoing aspirin desensitization | Physician-diagnosed | N-ERD [mean, SD] = 84.4 (13.4) ATA [mean, SD] = 91 (6) |
Cahill et al. 2019 [42] | USA | 40 | 13 | N/A | 47.0 (9.2) | 34.4 (15.3) | 38.1% | Stable asthma; non-smoker Exclusion: exacerbation requiring hospitalisation in preceding 6 weeks; pregnancy; breast-feeding; severe GORD, peptic ulcer, GI bleed or bleeding diathesis; antiplatelet or anticoagulant medication | Physician-diagnosed | N-ERD [mean, SD] = 91.2 (12.5) ATA [mean, SD] = 86.7 (10.9) |
Choi et al. 2021 [50•] | South Korea | 34 | 25 | N/A | 44.5 (10.3) | 49.2 (19.1) | 27.1% | NS | NS | N-ERD [mean, SD] = 86.6 (20.3) ATA [mean, SD] = 94.5 (15.3) |
Christie et al. 1991 [44] | UK | 6 | 5 | N/A | 31–55 | 24–30 | 36.4% | NS | NS | N-ERD [mean, SD] = 89 (16.4) ATA [mean, SD] = 93 (10.3) |
Christie et al. 1992 | Switzerland | 6 | 6 | N/A | 44.2 (6.9) | 35.5 (11.4) | 25% | NS | NS | N-ERD [mean, SD] = 78.3 (9.9) ATA [mean, SD] = 85.5 (7.7) |
Comhair et al. 2018 [9] | USA | 240 | 226 | 71 | 49.3 (12.4) | 49.7 (15.0) | 30.5% | Stable asthma Exclusion: exacerbation in preceding 6 weeks | NS | N-ERD [mean, SD] = 79.8 (20.1) ATA [mean, SD] = 86.6 (21.0) |
Gaber et al. 2008 [27] | Sweden | 11 | 10 | N/A | 46 (35–63) | 45.5 (27–56) | 33.3% | Stable asthma; non-smoker; suspicion of NSAID intolerance | NS | ≥ 70% |
Higashi et al. 2002 [17] | Japan | 13 | 10 | N/A | 54.8 (9.6) | 52.5 (16.2) | 56.5% | Stable asthma; non-smoker Exclusion: LRTI in preceding 6 weeks | ATS criteria; GINA guidelines | N-ERD [mean, SD] = 77.8 (19.3) ATA [mean, SD] = 75.3 (16.0) |
Higashi et al. 2003 [18] | Japan | 64 | 73 | 35 | 53.3 (21–79) | 51.2 (21–80) | 44.5% | Stable asthma Exclusion: cystic fibrosis; immotile cilia syndrome; autoimmune disease; LRTI in preceding 6 weeks | ATS criteria | N-ERD [mean, SD] = 77.3 (19.8) ATA [mean, SD] = 80.7 (21.5) |
Higashi et al. 2010 [28] | Japan | 10 | 7 | N/A | 45.1 (24–64) | 59.4 (24–73) | 11.8% | Adult subjects; suspicion of NSAID intolerance Exclusion: URTI in preceding 6 weeks; renal or liver dysfunction; hypertension; autoimmune disease | ATS criteria; GINA guidelines | N-ERD [mean, SD] = 80.2 (12.7) ATA [mean, SD] = 81.9 (14.3) |
Jerschow et al. 2016 [29] | USA | 16 | 13 | N/A | 37.8 (12.8) | 42.6 (8.7) | 41.4% | NS | Physician-diagnosed | N-ERD [mean, SD] = 73.0 (12.4) ATA [mean, SD] = 92.5 (33.9) |
Kawagishi et al. 2002 [19] | Japan | 48/60b | 51/100b | 33/110b | 54.1 (12.4) | 50 (17) | 42.5% | Stable asthma Exclusion: prescribed leukotriene receptor antagonist; LRTI in preceding 6 weeks | ATS criteria | NS |
Kumlin et al. 1992 [45] | Sweden | 9 | 15 | N/A | NS | NS | NS | NS | NS | NS |
Laidlaw et al. 2012 [43] | USA | 10 | 9 | 8 | 45 (20–65) | 37 (22–76) | 39.3% | Non-smoker | Physician-diagnosed | N-ERD [mean, SD] = 82 (9) ATA [mean, SD] = 88 (15) |
Mastalerz et al. 2001 [30] | Poland | 11 | 32 | 16 | 47.5 (10.1) | 37.5 (14.3) | 44.2% | Stable asthma | NS | ≥ 70% |
Mastalerz et al. 2002a [31] | Poland | 26 | 33 | N/A | 44.6 (29–61) | 45.8 (20–67) | 28.8% | NS | NS | N-ERD [mean, SD] = 72.3 (12.7) ATA [mean, SD] = 69.3 (14.3) |
Mastalerz et al. 2002b [48] | Poland | 19 | 21 | N/A | 40.8 (23–60) | 35.4 (19–60) | 62.5% | Stable asthma | NS | N-ERD [mean, range] = 85.3 (64.4–113.6) ATA [mean, range] = 86.3 (61.0–111.6) |
Mastalerz et al. 2008 [32] | Poland | 19 | 21 | 30 | 42.4 (13.3) | 43.6 (12.5) | 40% | Stable asthma Exclusion: exacerbation or LRTI in preceding 6 weeks | NS | ≥ 70% |
Mastalerz et al. 2015 [33] | Poland | 28 | 25 | N/A | 46.1 (14.0) | 43.8 (11.5) | 47.2% | Stable asthma Exclusion: exacerbation or LRTI in preceding 6 weeks | GINA guidelines | N-ERD [median, IQR] = 99.1 (15.6) ATA [median, IQR] = 98 (17.1) |
Micheletto et al. 2006 [34] | Italy | 67 | 51 | N/A | 41.8 (11.9) | 40.7% | Mild to moderate asthma; non-smoker; suspicion of aspirin intolerance and/or NP and/or CRS Exclusion: total obstruction of ≥ 1 nostril (inability to perform NPT) | NS | Mean (SD) = 80.1 (5.8) | |
Mita et al. 2001 [20] | Japan | 10 | 10 | N/A | 50.3 (16.4) | 46.8 (17.2) | 25% | Stable asthma | NS | ≥ 70% (except for 1 patient in ATA group) |
Mita et al. 2004 [35] | Japan | 7 | 6 | 18 | 49.9 (19.4) | 45.5 (18.0) | 53.8% | Stable asthma | NS | N-ERD [mean, SD] = 82.5 (14.3) ATA [mean, SD] = 99.2 (21.4) |
Mitsui et al. 2015 [21] | Japan | 30 | 21 | 14 | 52 (13) | 53 (17) | 19.6% | Stable asthma | ATS criteria | N-ERD [mean, SD] = 89 (20) ATA [mean, SD] = 92 (19) |
Obase et al. 2001 [46] | Japan | 7 | 7 | N/A | 39.7 (12.1) | 35.9 (10.3) | 35.7% | Stable asthma; non-smoker Exclusion: LRTI in preceding 6 weeks | NHLBI criteria | N-ERD [mean, SD] = 89.8 (5.8) ATA [mean, SD] = 90.7 (7.8) |
Obase et al. 2002 [47] | Japan | 6 | 7 | N/A | 29.5 (6.2) | 39.9 (11.9) | 30.8% | Stable asthma; non-smoker Exclusion: LRTI in preceding 6 weeks | NHLBI criteria | ≥ 80% |
Ono et al. 2011 [36] | Japan | 15 | 11 | 10 | 51 (42–65) | 55 (38–68) | 38.5% | Stable asthma; non-smoker | ATS criteria; GINA guidelines | N-ERD [median, range] = 71.6 (65.5–96.0) ATA [median, range] = 88.5 (61.2–98.2) |
Oosaki et al. 1997 [22] | Japan | 22 | 17 | 10 | NS | NS | 48.7% | Exclusion: history of smoking; severe asthma attack on study day; renal or liver dysfunction; ischaemic heart disease; autoimmune disease | ATS criteria | NS |
Pezato et al. 2016 [37] | Poland | 20 | 18 | N/A | 46 (19) | 44 (19) | 26.3% | NS | GINA guidelines | N-ERD [mean, SD] = 94.2 (15.8) ATA [mean, SD] = 88.3 (9.2) |
Sanak et al. 2004 [38] | Poland | 14 | 20 | 10 | 41.4 (13.9) | 36.5 (12.3) | 64.7% | Stable asthma Exclusion: exacerbation in preceding 6 weeks | NS | N-ERD [mean, SD] = 81.5 (12.5) ATA [mean, SD] = 92.6 (14.9) |
Sanak et al. 2010 [16] | Poland | 41 | 83 | 50 | 44.5 (21–66) | 37.1% | NS | NS | NS | |
Smith et al. 1992 [56] | UK | 10 | 31 | 17 | 21–54 | 18–34 | 75.6% | NS | Clinical history; reversibility | N-ERD [mean, SD] = 97 (10) ATA [mean, SD] = 86 (15) |
Swierczynska-Krepa et al. 2014 [40] | Poland | 20 | 14 | N/A | 46 (19) | 49.5 (15) | 29.4% | Aged 18–65 Exclusion: history of life-threatening anaphylactic reactions precipitated by NSAIDs; autoimmune disease; severe systemic disease; neoplasm; pregnancy | GINA guidelines | N-ERD [median, IQR] = 88.7 (17.8) ATA [median, IQR] = 92.5 (30.9) |
Yamaguchi et al. 2011 [23] | Japan | 15 | 16 | 10 | 53.9 (16.0) | 59.2 (20.3) | 45.2% | Adult subjects Exclusion: LRTI in preceding 6 weeks; cardiovascular disease; renal or liver dysfunction | ATS criteria | N-ERD [mean, SD] = 81.7 (16.9) ATA [mean, SD] = 88.0 (20.1) |
Yamaguchi et al. 2016 [24] | Japan | 15 | 15 | 28 | 51.1 (14.5) | 50.6 (13.3) | 33.3% | Stable asthma; CRS Exclusion: URTI in preceding 6 weeks; cystic fibrosis; immotile cilia syndrome; Churg-Strauss syndrome; autoimmune disease | ATS criteria | NS |
Study | Reference standard | Challenge agent | Challenge undertaken? | Criteria for N-ERD | Method of uLTE4 analysis | Original units of uLTE4 | Urine sampling |
---|---|---|---|---|---|---|---|
Ban et al. 2016 [39] | Challenge or positive history | Lysine aspirin inhalation | Retrospectively | Fall in FEV1 of ≥ 20% relative to baseline | MS | pmol/mg Cr | Spot urine |
Ban et al. 2021 [49] | Challenge or positive history | Lysine aspirin inhalation | Retrospectively | Fall in FEV1 of ≥ 20% relative to baseline | MS | pg/mg Cr | Spot urine |
Bochenek et al. 2003 [25] | Challenge | Oral aspirin | Retrospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Bochenek et al. 2018 [8] | Challenge or positive history | NS | Retrospectively | Asthma exacerbation precipitated by NSAID administration | C-EIA | pg/mg Cr | Spot urine |
Cahill et al. 2015 [41] | Positive history | N/A | N/A | Characteristic reactions upon ingestion of COX-1 inhibitors | MS | pmol/mg Cr | Spot urine |
Cahill et al. 2019 [42] | Challenge | Oral aspirin | Retrospectively | NS | MS | ng/mg Cr | Spot urine |
Choi et al. 2021 [50•] | Challenge | Lysine aspirin inhalation | Retrospectively | NS | MS | ng/mg Cr | Spot urine |
Christie et al. 1991 [44] | Challenge | NS | Retrospectively | Fall in FEV1 of ≥ 15% relative to baseline | RIA | pg/mg Cr | Spot urine × 2 (10 days apart) |
Christie et al. 1991 [44] | Challenge | Oral aspirin | Retrospectively | Fall in FEV1 of ≥ 15% relative to baseline | RIA | pg/mg Cr | Spot urine × 2 (1 week apart) |
Comhair et al. 2018 [9] | Challenge or positive history | NS | Retrospectively | Asthma exacerbation precipitated by NSAID administration | C-EIA | pg/mg Cr | Spot urine |
Gaber et al. 2008 [27] | Challenge | Lysine aspirin inhalation | Prospectively | Fall in FEV1 of ≥ 20% compared with post-saline FEV1 | C-EIA | ng/mmol Cr | Spot urine |
Higashi et al. 2002 [17] | Challenge or positive history | NS | Retrospectively | Asthma exacerbation precipitated by NSAID administration | A-EIA | pg/mg Cr | Spot urine |
Higashi et al. 2003 [18] | Challenge or positive history | NS | Retrospectively | Severe bronchoconstriction and nasal symptoms precipitated by ingestion of ≥ 2 different NSAIDs | A-EIA | pg/mg Cr | Spot urine |
Higashi et al. 2010 [28] | Challenge | Lysine aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Jerschow et al. 2016 [29] | Challenge | Oral aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Kawagishi et al. 2002 [19] | Challenge or positive history | NS | Retrospectively | Asthma exacerbation precipitated by NSAID administration | A-EIA | pg/mg Cr | Spot urine |
Kumlin et al. 1992 [45] | Challenge or positive history | NS | Retrospectively | NS | RIA | ng/mmol Cr | Spot urine |
Laidlaw et al. 2012 [43] | Challenge | Oral aspirin | Retrospectively | Fall in FEV1 of ≥ 15% relative to baseline | MS | ng/mg Cr | Spot urine |
Mastalerz et al. 2001 [30] | Challenge | Lysine aspirin inhalation | Retrospectively | NS | C-EIA | pg/mg Cr | Spot urine |
Mastalerz et al. 2002a [31] | Challenge | Lysine aspirin inhalation; oral aspirin | Retrospectively | NS | C-EIA | pg/mg Cr | Spot urine |
Mastalerz et al. 2002b [48] | Challenge | Oral aspirin | Retrospectively | NS | C-EIA | pg/mg Cr | Spot urine |
Mastalerz et al. 2008 [32] | Challenge | Oral aspirin | Retrospectively | NS | C-EIA | pg/mg Cr | Spot urine |
Mastalerz et al. 2015 [33] | Challenge | Oral aspirin | Retrospectively | NS | C-EIA | pg/mg Cr | Spot urine |
Micheletto et al. 2006 [34] | Challenge | Lysine aspirin nasal | Prospectively | Nasal resistance increased > 40% in at least one nostril relative to baseline; volume of one nostril decreased > 10% from baseline | C-EIA | pg/mg Cr | Spot urine |
Mita et al. 2001 [20] | Challenge | Lysine aspirin intravenous | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | A-EIA | pg/mg Cr | Spot urine |
Mita et al. 2004 [35] | Challenge | Lysine aspirin intravenous | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Mitsui et al. 2015 [21] | Challenge | Lysine aspirin inhalation; oral aspirin | Retrospectively | NS | A-EIA | pg/mg Cr | Spot urine |
Obase et al. 2001 [46] | Challenge | Oral aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | RIA | pg/mg Cr | Spot urine |
Obase et al. 2002 [47] | Challenge | Oral aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | RIA | pg/mg Cr | Spot urine |
Ono et al. 2011 [36] | Challenge | NS | Retrospectively | NS | C-EIA | pg/ml Cr | Spot urine |
Oosaki et al. 1997 [22] | Positive history | N/A | N/A | History of aspirin sensitivity | A-EIA | pg/mg Cr | Spot urine |
Pezato et al. 2016 [37] | Challenge | Oral aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/ml Cr | Spot urine |
Sanak et al. 2004 [38] | Challenge | Oral aspirin | Retrospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Sanak et al. 2010 [16] | Challenge | NS | Retrospectively | NS | C-EIA; MS | pg/mg Cr | Spot urine |
Smith et al. 1992 [56] | Challenge | NS | Retrospectively | Fall in FEV1 of ≥ 15% relative to baseline | RIA | pg/mg Cr | Spot urine |
Swierczynska-Krepa et al. 2014 [40] | Challenge | Oral aspirin | Prospectively | Fall in FEV1 of ≥ 20% relative to baseline | C-EIA | pg/mg Cr | Spot urine |
Yamaguchi et al. 2011 [23] | Challenge | Lysine aspirin intravenous | Retrospectively | Fall in FEV1 of ≥ 20% relative to baseline | A-EIA | pg/mg Cr | Spot urine |
Yamaguchi et al. 2016 [24] | Challenge or positive history | NS | Retrospectively | Asthma exacerbation precipitated by NSAID administration | A-EIA | pg/mg Cr | Spot urine |