Table 2. Patient reported outcomes, patient reported outcome measures and genetic associations assessed.
| First author’s name & Year | Design | Participants | Population/Ethnicity | Patient Reported Outcome (PRO) | Patient Reported Outcome Measure (PROM) | Genes of interest | Single Nucleotide Polymorphisms | Results |
|---|---|---|---|---|---|---|---|---|
| Bleecker et al, (2012) [16] | Intervention, pre/post study |
Study I: n = 1483 Gly/Gly: n = 575 (370 Male, 64%, 63±9 yrs) Smoking status: Ex/current: 319/256 Pack-years: n.a. FEV1 (%pred): 34.5±9.4 COPD grades (I/II/III/IV): n.a. Arg/Gly: n = 685 (433 Male, 63%, 63±9 yrs) Smoking status: Ex/current: 396/289 Pack-years: n.a. FEV1 (%pred): 34.4±9.2 COPD grades (I/II/III/IV): n.a. Arg/Arg: n = 223 (139 Male, 62%, 63±10 yrs) Smoking status: Ex/current: 130/93 Pack-years: n.a. FEV1 (%pred): 34.4±9.3 COPD grades (I/II/III/IV): n.a. Study II: n = 1383 Gly/Gly: n = 533 (373 Male, 70%, 64±9 yrs) Smoking status: Ex/current: 309/224 Pack-years: n.a. FEV1 (%pred): 33.9±9.1 COPD grades (I/II/III/IV): n.a. Arg/Gly: n = 635 (451 Male, 71%, 63±9 yrs) Smoking status: Ex/current: 373/262 Pack-years: n.a. FEV1 (%pred): 34.6±9.7 COPD grades (I/II/III/IV): n.a. Arg/Arg: n = 215 (133 Male, 62%, 63±9 yrs) Smoking status: Ex/current: 117/98 Pack-years: n.a. FEV1 (%pred): 34.1±9.6 COPD grades (I/II/III/IV): n.a |
American; European; South African |
HRQOL; Symptoms |
SGRQ BCSS |
ADRB2 | rs1042713 | BCSS: Study I (p≥0.378); Study II (p≥0.133) SGRQ: Study I (p = 0.909); Study II (p = 0.648) |
| Ishii et al, (2014) [25] | Observational study | n = 135 (127 Male, 94%, 69.3±7.9 yrs) Smoking status: Ex/current: 113/22 Pack-years: 74.5 ±47.6 FEV1 (%pred): 57.8±20.3 COPD grades (I/II/III/IV): 22/61/41/11 |
Japanese | Exacerbation frequency | Diary | GC | rs4588 rs7041 |
Exacerbation Frequency: rs4588 SNP: p = 0.0048; rs7041 SNP: p = 0.56. |
| Ishii et al, (2011) [21] | Observational study | n = 247: COPD (228 Male, 92%, 69.7±8.1 yrs) Smoking status; Ex/Current: 207/40 Pack-years: 69.4±42.6 FEV1 (%pred): 58.3±19.5 COPD grades(I/II/III/IV): n.a |
Japanese | Depressive symptoms | HADS | SLC6A4 | rs3794808 rs140701 rs140700 rs2020939 rs2020936 |
rs3794808, p(adjusted)/ Depression score HADS: Trend: 0.016; Genotype: 0.052 rs140701, p(adjusted)/ Depression score HADS: Trend: 0.093; Genotype: 0.246 rs140700, p(adjusted)/ Depression score HADS: Trend: 0.559; Genotype: 0.844 rs2020939, p(adjusted)/ Depression score HADS: Trend: 0.13; Genotype: 0.261 rs2020936, p(adjusted)/ Depression score HADS: Trend: 0.903; Genotype: 0.966 |
| Lin et al, (2011) [22] | Observational study | n = 84: Non-MBL -deficient genotypes (27 Male, 21%, 66.5±10.9 yrs) Smoking status: Ex/current: 60/24 Pack-years: 46 FEV1 (%pred): 46 COPD grades(I/II/III/IV): 2/28/39/17 n = 12: MBL-deficient genotypes (6 Male,50%,68.9±10.3 yrs) Smoking status: Ex/current: 10/2 Pack-years: 50 FEV1 (%pred): 41 COPD grades(I/II/III/IV): 1/4/6/1 |
Han Chinese (Taiwan) | Exacerbation frequency | Patient interviews | MBL2 | rs11003125 rs7096206 rs1800451 rs5030737 rs1800450 |
Frequency of infective exacerbation (times) in: Non-MBL-Deficient genotypes (n = 84): 3.52±0.78 Total episodes: 296 MBL-Deficient Genotypes (n = 12): 4.75±1.22 Total episodes: 57 p˂0.0001 |
| Mandal et al, (2015) [14] | Observational study | n = 277 (190 Male, 84%, 67.8 ± 9.5 yrs) Smoking status: Ex/current: 203/74 Pack-years: Median 50 IQR (35–80) FEV1 (%pred): 48.2±17.5 COPD grades(I/II/III/IV): 0/129/104/40 |
European | Exacerbation frequency | Contacting the patients | MBL2 | HL (-550 G>C; rs11003125) YX (-221 G>C; rs7096206) PQ (+4 C>T; rs7095891) A/D (+223 C>T; rs5030737) A/B (+230 G>A; rs1800450) A/C (+239 G>A; rs1800451) |
MBL2 haplotype: HYPA Infrequent exacerbation (n = 87): Frequency: 0.282; Frequent exacerbation (n = 85): Frequency: 0.346; p = 0.13 MBL2 haplotype: LYQA Infrequent exacerbation (n = 75): Frequency: 0.243; Frequent exacerbation (n = 53): Frequency: 0.215; p = 0.49 MBL2 haplotype: LYPA Infrequent exacerbation (n = 30): Frequency: 0.097; Frequent exacerbation (n = 15): Frequency: 0.061; p = 0.16 MBL2 haplotype: LXPA Infrequent exacerbation (n = 71): Frequency: 0.230 Frequent exacerbation (n = 50): Frequency: 0.303; p = 0.50 MBL2 haplotype: LYPB Infrequent exacerbation (n = 27): Frequency: 0.087; Frequent exacerbation (n = 19): Frequency: 0.077; p = 0.77 MBL2 haplotype: HYPD Infrequent exacerbation (n = 10): Frequency: 0.032 Frequent exacerbation (n = 21): Frequency: 0.085; p = 0.01 MBL2 haplotype: LYQC Infrequent exacerbation (n = 8): Frequency: 0.026; Frequent exacerbation (n = 3): Frequency: 0.012; p = 0.39 |
| Pillai et al, (2010) [15] | Observational study | n = 1,609 (1086 Male, 67.5%, 63.8± 7.1 yrs) Smoking Status: Ex/Current, %: 64.5/35.5 Pack-years: 50.9±28 FEV1: 48.1±15.6 COPD grades(I/II/III/IV): n. a |
European; Canadian; New Zealanders; Norwegians; Ukrainians; American |
Exacerbation Frequency | Retrospective exacerbations: questionnaires Prospective exacerbations: telephone calls. |
HHIP, FAM13A CHRNA3/5 | rs13118928 rs8034191 rs7671167 |
Prior Exacerbations: rs13118928(HHIP): IRR: 0.877; 95% IC: 0.78–0.975; p = 0.015 rs8034191(CHRNA): IRR: 0.971; 95% IC: 0.869–1.084; p = 0.598 rs7671167(FAM13A): IRR: 1.081; 95% IC: 0.978–1.195; p = 0.129 Prospective exacerbations rs13118928(HHIP): IRR: 0.906; 95 IC: 0.832–0.987; p = 0.024 rs8034191(CHRNA): IRR: 1.017; 95% IC: 0.930–1.113; p = 0.709 rs7671167(FAM13A): IRR: 1.028; 95% IC: 0.943–1.22; p = 0.528. |
| Quint et al, (2011) [23] | Observational study | n = 204 (119 Male, 58%, 70.7 ±11.1 yrs) Smoking status: Ex/current: 152/52 Pack-years: 51.6±38.7 FEV1 (l): 48.2±19.9 COPD grades(I/II/III/IV): 14/83/73/34 |
European | Exacerbation frequency |
Diary | SERPINA1 | 11478G>A polymorphism | Exacerbation α1-antitrypsin: (GG): Median = 2.01 IQR (1.54–2.99); (GA/AA): Median = 1.98 IQR (1.67–2.12); GG vs. GA/AA: p = 0.75 baseline vs. exacerbation: (GG): p = 0.87; (GA/AA): p = 0.92 |
| Quint et al, (2012) [24] | Observational study | n = 97 (61 Male, 62.9%, 71.8±8.8 yrs) Smoking status: Ex/current: 72/25 Pack-years: 50.7±34.2 FEV1:(%pred): 50.3±19.7 COPD grades(I/II/III/IV): n.a |
European British) |
Exacerbation frequency | Diary | VDR | rs1544410 rs731236 rs2228570 |
rs1544410(Bsml): Frequent exacerbators (n = 28): 3 (10.7%)–BB genotype; 12 (42.9%)–Bb genotype; 13 (46.4%)–Bb genotype. Infrequent exacerbators (n = 68): 15 (22.1%)–BB genotype; 26 (38.2%)–Bb genotype; 27 (39.7%)–Bb genotype p = 0.43 rs731236(Taql): Frequent exacerbators (n = 28): 10 (38.5%)–TT genotype; 13 (50%)–Tt genotype; 3 (11.5%)–Tt genotype. Infrequent exacerbators (n = 68): 24 (36.4%)–TT genotype; 29 (43.9%)–Tt genotype; 13 (19.7%)–Tt genotype p = 0.64 rs2228570(Fokl): Frequent exacerbators (n = 28): 10 (35.7%)–FF genotype; 14 (50,0%)–Ff genotype; 4 (14.3%)–Ff genotype. Infrequent exacerbators (n = 68): 21 (30.9%)–FF genotype; 38 (55.9%)–Ff genotype; 9 (13.2%)–Ff genotype p = 0.87 |
| Takabatake et al, (2006) [19] | Observational study | n = 276 (276 Male, 100%, 72.9 ± 1.6 yrs) Smoking status: Ex/current: 276/0 Pack-years: n.a. FEV1: (%pred) n.a. COPD grades(I+II/III+IV): n.a. |
Japanese | Exacerbation severity | Questionnaire | CCL1 | rs2282691 | Kaplan-Meier Genotype: AA; No. of patients:60 No. of events: 9 Survival Time, mo (95% CI): 28 (27–30) Log-Rankk Statistic: AA vs AT: 1.51 (0.2189) Genotype: AT; No. of patients: 132 No. of events:12 Survival Time, mo (95% CI): 29 (28–30) Log-Rankk Statistic: AA vs TT: 7.67 (0.0056) Genotype: TT; No. of patients: 84 No. of events:2 Survival Time, mo (95% CI): 30 (29–30) Log-Rankk Statistic: AT vs TT: 3.54 (0.0600) Cox Proportional Hazards Regression Model TT: n = 84; p = n.a.; OR (95% CI) = 1 AT: n = 132; p = 0.066; OR (95% CI) = 4.09 (0.91–18.32) AA: n = 60; p = 0.023; OR (95% CI) = 5.93 (1.28–27.48) |
| Umeda et al, (2008) [17] | Intervention pre/post study | n = 44: n = 22: Arg/Arg (21 Male, 95%, 73±8 yrs) Smoking status: Ex/current: 21/1 Pack-years: n.a FEV1: (%pred) Median 50.7 Interquartile range (38.1–67.2) COPD grades(I/II/III/IV): n.a n = 22: non-Arg/Arg (19 Male, 86%, 68±8 yrs) Smoking status: Ex/current: 21/1 Pack-years: n.a FEV1 (%pred) Median 63.9 Interquartile range (42.3–89.0) COPD grades(I/II/III/IV): n.a |
Japaanese | Quality of life | SGRQ | ADRB2 | rs1042713 |
Total Score: Arg/Arg: -16.9; non-Arg/Arg: -8.1 P = 0.05 Impact score: Arg/Arg: -19.8; non- Arg/Arg: 22 p<0.001 |
| Yang et al, (2003) [20] | Observational study | n = 82 (52 Male,63%,69±8 yrs) Smoking status: Ex/current: n.a/n. a Pack-years: Median 54 IQR (39–66) FEV1:(%pred): 41±14 COPD grades(I/II/III/IV): n.a |
Australian | Exacerbation frequency | Telephone call | MBL2 | rs1800450 |
OR 4.9; 95% IC: 1.7–14.4; p = 0.0037, pcorrected = 0.011 |
| Zhang et al, (2015) [26] | Intervention pre/post study | n = 219 (194 Male, 88.6%,70.2±7.2 yrs) Smoking status: n.a. Pack-years: 28.1±7.2 FEV1:(%pred): 51.8±15.9 COPD grades(I/II/III/IV): n.a |
Chinese | Respiratory Health status | SGRQ | EPHX1 | rs1051740 (slow allele) rs2234922 (fast allele) |
Total score Slow activity group: Baseline: 36.9±12.1; After NAC: 35.1±12.7 p>0.05 Fast activity group: Baseline: 38.0±13.1; After NAC: 35.8±14.8 p>0.05 Symptom score Slow activity group: Baseline: 40.9±12.3; After NAC: 37.8±13.1 p = 0.033 Fast activity group: Baseline: 41.7±13.5; After NAC: 38.7±15.4 P>0.05 Activity score Slow activity group: Baseline: 47.2±12.1; After NAC: 45.8±12.8 p>0.05 Fast activity group: Baseline: 48.7±13.3; After NAC: 49.1±14.0 p>0.05 Impact score Slow activity group: Baseline: 26.3±10.9; After NAC: 24.9±11.5 p>0.05 Fast activity group: Baseline: 28.1±11.7; After NAC: 26.5±12.1 p>0.05 |
| Zhang et al, (2015) [18] | Intervention pre/post study | n = 368 L+: n = 154 (140 Male, 90.9%, 68.7±6.3 yrs) Smoking status: Ex/current: 123/31 Pack-years: 24.5±6.6 FEV1: (%pred): 56.4±14.8 COPD grades(I/II/III/IV): n.a L-: n = 214 (193 Male,90.2%,69.3±5 yrs) Smoking status: Ex/current: 170/44 Pack-years: 24.7±5.6 FEV1: (%pred) 56.6±19.2 COPD grades(I/II/III/IV): n.a |
Chinese | Respiratory health status | SGRQ | HO-1 | (GT)n polymorphism: | Total score Baseline—L+ group:35.0±11.6; L- group: 35.1±10.7 16 weeks—L+ group:35.7±9.6; L- group: 35.9±11.3 32 weeks—L+ group:36.2±11.2; L- group:36.4±12.4 48 weeks—L+ group:37.4±10.4; L- group: 37.8±9.0 p = 0.18 Activity score Baseline—L+ group:46.7±13.9; L- group:46.2±14.5 16 weeks—L+ group:46.5±14.1; L- group: 46.3±11.0 32 weeks—L+ group:46.8±8.3; L- group: 46.7±12.2 48 weeks—L+ group:46.3±11.5; L- group: 47.4±15.5 p = 0.02 Symptom score Baseline—L+ group:40.5±10.8; L- group: 40.1±12.3 16 weeks—L+ group:40.8±8.4; L- group: 40.8±15.1 32 weeks—L+ group:41.1±6.9; L- group: 41.6±10.3 48 weeks—L+ group:41.7±13.7; L- group: 41.6±9.7 p = 0.86 Impact score Baseline—L+ group:25.6±10.1; L- group: 26.0±11.4 16 weeks—L+ group:25.9±7.1; L- group: 26.5±8.6 32 weeks—L+ group:25.7±11.3; L- group: 26.9±10.5 48 weeks—L+ group:25.9±8.9; L- group: 26.7±13.4 p = 0.09 |
All values are presented as mean ± standard error, unless otherwise stated.
M- male; yrs- years; SNP- single nucleotide polymorphism; FEV1- forced expiratory volume in 1 second; l- liters; %pred- % predicted; COPD- chronic obstructive pulmonary disease n.a- not applicable; SE- standard error; IRR- Incidence rate ratio; IC- Confidence interval; OR- Odds ratio; SGRQ- St. George Respiratory Questionnaire; BCSS- Breathlessness, cough and sputum scale; HADS—Hospital anxiety and depression scale. ´
Significant results presented in bold.