170 6 Chapter 6 2017), and one in Western Asia (total 896 participants) (Wakabayashi 2011). Tests for subgroup di erences showed a statistically signi cant di erence in e ect between groups (Chi² = 16.88, df = 5, P = 0.005) (Analysis 1.7). Closer inspection of the subgroups showed no di erences between IDM and control for the Northwest Europe and Oceania subgroups. Heterogeneity remained substantial in the North America subgroup (I² = 56%) and the Southern Europe subgroup (I² = 61%) and were considerable in the East Asia subgroup (I² = 91%). Results for these subgroups should therefore be interpreted with caution. 1.2. SGRQ total score - long-term Four studies including 1090 participants measured the long-term e ect on SGRQ total score at 18 months (Gottlieb 2011), or at 24 months (Kalter-Leibovici 2018; Titova 2017; van Wetering 2010). No statistically signi cant di erence was noted between IDM and usual care (MD -0.69, 95% CI -3.31 to 1.93; I² = 31%) (Analysis 1.3; Figure 3). 1.3. SGRQ domain scores - short-term Eleven studies with a total population of 1320 to 1327 participants reported scores on the SGRQ domains of symptoms, activity, and impact. For all domains, heterogeneity was substantial (I² between 46% and 71%) (Analysis 1.1). We found the following results: symptoms domain (MD -1.56, 95% CI -6.66 to 2.53), activity domain (MD -3.04, 95% CI -5.80 to -0.28), and impact domain (MD -3.76, 95% CI -5.94 to -1.57). Sensitivity analysis with only high-quality studies showed a statistically signi cant e ect in favour of IDM for the activity domain (MD -3.63, 95% CI -5.66 to -1.61; I² = 0%) and for the impact domain (MD -4.1, 95% CI -6.30 to -1.90; I² = 31%) of the SGRQ. There was no signi cant e ect on the SGRQ symptoms domain (MD -1.94, 95% CI -5.26 to 1.38; I² = 41%). A portion of the heterogeneity could be explained by the di erence in quality of studies, as heterogeneity decreased signi cantly across all domains when only highquality studies were pooled (Table 7). 1.4. SGRQ domain scores - medium-term Twelve studies with a total population of 2608 to 2628 participants reported scores on the SGRQ domains after 6 to 15 months’ follow-up. We found the following results: symptoms domain: MD -3.88, 95% CI -7.75 to -0.02; I² = 79%; activity domain: MD -2.57, 95% CI -5.53 to 0.38; I² = 71%; and impact domain: MD -3.34, 95% CI -6.26 to -0.41; I² = 0%. Sensitivity analysis did not explain the heterogeneity observed (I² between 71% and 79%) but did show a statistically signi cant e ect in favour of IDM. E ects were statistically signi cant for all domains (Analysis 1.2; Table 7). 1.5. SGRQ domain scores - long-term Three studies measured the long-term e ect on SGRQ domains at 18 months (Gottlieb 2011), or at 24 months (Titova 2017; van Wetering 2010). As with the SGRQ total score,
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