TABLE 2

Mild asthma studies grouped by study type (RCT or observational/other) and by definition of mild asthma

Study (year) [ref.]	Age range or average age years	Treatment duration	Placebo		Exacerbation definition	Baseline exacerbation data	Patients with history of exacerbation not excluded^#
Study (year) [ref.]	Age range or average age years	Treatment duration	Yes n, treatment allowed	No	Exacerbation definition	Baseline exacerbation data	Patients with history of exacerbation not excluded^#
RCTs
Category 1: RCTs that primarily defined mild asthma by treatment level
Bateman et al. (2018) [26]	12–83	52 weeks		✓	✓	✓
Camargos et al. (2018) [31]	10.6 (2.8)^¶, 9.9 (2.7)^¶	6 weeks		✓	✓
O’Byrne et al. (2018) [38]	12–85	52 weeks		✓	✓
Category 2: RCTs that primarily defined mild asthma by symptom frequency
Martinez et al. (2011) [36]	5–18	44 weeks	74 P bid + P/ALB rescue		✓	✓	✓
Pauwels et al. (2003) [41]	5–66	3 years	3568 P + usual asthma medication		✓	✓	✓
Wongtim et al. (1995) [80]	33.2 (7.46)^¶, 32.8 (8.6)^¶	8 weeks	10				✓
Category 3: RCTs that primarily defined mild asthma with a composite definition of FEV₁ ≥80% pred and symptoms <daily
Basyigit et al. (2004) [81]	38 (8.2)^¶, 42.4 (9.6)^¶, 45.5 (10.9)^¶	8 weeks		✓			✓
Bousquet et al. (2005) [29]	15–80	48 weeks (12 DB, 36 OL)		✓	✓		✓
Chrousos et al. (2005) [82]	18–65	14 days		✓			✓
Chuang et al. (2007) [83]	6–14	8 weeks		✓			✓
Chuchalin et al. (2005) [33]	6–87	12 months		✓	✓		✓
Chuchalin et al. (2008) [32]	12–79	52 weeks	315		✓		✓
Currie et al. (2003) [84]	36 (4)⁺	2×3 weeks		✓			✓
Garcia Garcia et al. (2005) [35]	6–14	12 months		✓	✓		✓
Karaman et al. (2004) [85]	8–14	12 weeks		✓			✓
Maiti et al. (2011) [86]	18–70	4 weeks		✓			✓
Ng et al. (2007) [37]	6–14	2×8 weeks		✓	✓
Reddel et al. (2008) [42]	18–80	11 months	21		✓
Renzi et al. (2010) [43]	≥12	24 weeks		✓	✓		✓
Riccioni et al. (2002) [87]	26.9 (12.3)^¶, 26.7 (8.6)^¶, 28.2 (10.1)^¶	16 weeks		✓
Shimoda et al. (2005) [88]	36.2 (12.8)^¶, 35.6 (14.4)^¶	6 months		✓			✓
Tamaoki et al. (2008) [89]	≥21	8 weeks		✓			✓
Vatrella et al. (2002) [90]	18–48	16 weeks		✓			✓
Zeiger et al. (2005) [91]	15–85	48 weeks (12 DB, 36 OL)^§		✓			✓
Zietkowski et al. (2006) [92]	45.2 (10.9)^ƒ, 42 (14)^ƒ, 51 (7.6)^ƒ	12 weeks		✓			✓
Category 4: RCTs that primarily defined mild asthma with a composite definition of FEV₁ approximately >60–80% and symptoms <daily
Berger et al. (2009) [48]	≥12	16 weeks	177		✓
Boulet et al. (2000) [93]	≥12	12 weeks		✓			✓
Drazen et al. (1996) [34]	12–55	20 weeks (16 weeks active treatment + 4 weeks withdrawal (OL ALB as needed))	129 P + ALB as needed^##		✓		✓
Herjavecz et al. (1999) [55]	17–67	22 weeks (6 DB; 16 OL)		✓		✓	✓
O'Byrne et al. (2001) [39]	≥12	1 year	Group A: 239		✓		✓
O'Sullivan et al. (2003) [94]	19–50	2×8 weeks		✓			✓
Papi et al. (2007) [40]	18–65	6 months	118 P bid + ALB 100 μg as needed		✓		✓
Peters et al. (2007) [56]	≥6	16 weeks		✓		✓	✓
Stone et al. (2001) [95]	≥16	4 weeks		✓			✓
Tattersfield et al. (2001) [45]	20–60	2 years		✓	✓
Tomlinson et al. (2005) [46]	20–60	12 weeks		✓	✓		✓
van Grunsven et al. (1996) [47]	≥30	2 years		✓	✓		✓
Verberne et al. (1996) [58]	7–16	4 months		✓		✓	✓
Vermetten et al. (1999) [96]	18–66	12 weeks		✓			✓
Woodcock et al. (2002) [59]	18–65	6 weeks		✓			✓
Category 5: RCTs that defined mild asthma by other/miscellaneous criteria
Arets et al. (2002) [23]	5–10	12 weeks	33		✓		✓
Boushey et al. (2005) [28]	18–65	1 year		✓	✓		✓
Villaran et al. (1999) [97]	14–45	8 weeks		✓			✓
Category 5: RCTs that did not describe their patients as having “mild asthma” but included patients with disease characteristics similar to the categories described above
Bailey et al. (2008) [24]	12–65	52 weeks		✓	✓		✓
Barnes et al. (2007) [98]	≥12	12 weeks		✓			✓
Bateman et al. (2012) [25]	≥12	8 weeks	94		✓	✓	✓
Busse et al. (2001) [30]	>15	24 weeks		✓	✓		✓
Busse et al. (2001) [53]	12–75	12 weeks	114
van der Molen et al. (1998) [99]	18–50	12 weeks		✓			✓
Category 6: RCTs that included patients <5 years old
Bisgaard et al. (2005) [27]	2–5	48 weeks	271		✓	✓	✓
Shah et al. (2014) [100]	2–18	12 weeks		✓			✓
Szefler et al. (2007) [44]	2–8	52 weeks		✓	✓		✓
Category 6: RCTs that included patients <5 years old that did not describe their patients as having “mild asthma” but included patients with disease characteristics similar to mild asthma
Robertson et al. (2007) [21]	2–14	12 months	113			✓	✓
Skoner et al. (2005) [57]	2–5	3 weeks	50			✓
Observational/other
Category 1: Observational/other studies that primarily defined mild asthma by treatment level
Ding and Small (2017) [49]	≥12	–		NA	✓		✓
Friedman et al. (2010) [50]	12–25	–		NA	✓
Friedman et al. (2010) [51]	12–65	–		NA	✓
McIvor et al. (2009) [22]	≥6	Survey + 6-week treatment		NA		✓	✓
Navaratnam et al. (2009) [52]	12–65	–		NA	✓
Category 3: Observational/other studies that primarily defined mild asthma with a composite definition of FEV₁ ≥80% and symptoms<daily
Giraud et al. (2006) [54]	≥18	4–8 weeks		NA		✓	✓
Lai et al. (2003) [61]	Total (not just mild asthma) Children: 7.4 (3.8)^¶Adults: 40.5 (18.5)^¶	–		NA		✓
Category 4: Observational/other studies that primarily defined mild asthma with a composite definition of FEV₁ approximately >60–80% and symptoms<daily
Soyer et al. (2009) [60]	6–18	–		NA			✓
Category 6: Observational/other studies that included patients <5 years old
König et al. 1996 [62]	≤17	–		NA		✓	✓
Robertson et al. (1992) [63]	≤20	–		NA			✓

RCT: randomised controlled trial; bid: twice daily; P: placebo; ALB: albuterol; DB: double-blind; OL: open-label; FEV₁: forced expiratory volume in 1 s; NA: not applicable. ^# History of exacerbations considered to be exacerbation, hospitalisation or emergency department visit or oral corticosteroid use that occurred prior to enrolment/screening (RCTs or prospective observational studies) or in the pre-index period (retrospective studies); ^¶: mean (sd) age in years; ⁺: mean (se) age. ^§: 10% of participants (determined at randomisation) switched therapies to preserve the masking in the preceding period; ^ƒ: median (range) age; ^##: no dose given.