Table 2.

Challenge criteria and methodology of uLTE₄ analysis in included studies (n = 36)

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

A-EIA Amersham-enzyme immunoassay, C-EIA Cayman-enzyme immunoassay, COX-1 cyclooxygenase-1, FEV₁ forced expiratory volume in one second, MS mass spectrometry, N-ERD NSAIDs exacerbated respiratory disease, NSAID non-steroidal anti-inflammatory drug, RIA radioimmunoassay, uLTE4 urinary leukotriene E4, N/A not applicable, NS not specified