Long-Term Risk of Mortality Associated with Isolation of Pseudomonas aeruginosa in COPD: A Systematic Review and Meta-Analysis

Figures & data

Figure 1 Flow chart of study selection.

Table 1 Characteristics of the Studies Included

Authors, Year	Ref.	Country	Recruiting Period	N included	Design	Follow-Up (Months)
Almagro et al, 2012	16	Spain	June 2003 – September 2004	181	P cohort	36
Bouquet et al, 2020	27	Bulgaria, Czech Republic, USA	Fall 2011 - spring 2014	200	P cohort	36
Boutou et al, 2014	18	UK	2000–2012	132	R cohort	NR
Choi et al, 2018	26	Korea	January 2011 - May 2017	104	R case-control	0.5
Eklöf et al, 2020	15	Denmark	January 2010 - October 2017	22.053	P cohort	36
Jacobs et al, 2020	17	USA	1994–2014	181	P cohort	42.5
Martínez-García et al, 2021	10	Spain	January 2004 – February 2007	170	P cohort	85
Rodrigo-Troyano et al, 2018	19	Spain	March 2012 - March 2015	207	P cohort	12

Abbreviations: Ref, number of the reference in the reference list; NR, Not reported; P, Prospective; R, Retrospective; USA, United States of America; UK, United Kingdom.

Table 2 Patient Characteristics

Author, Year (Ref.)	Male, n (%)	Age, Years	COPD Severity	FEV1 (%)	Smokers^$, n (%)	BMI	Bronchiec-tasis, n (%)	Charlson Index
Almagro et al, 2012 (16)	172 (95)	72 ± 9.8	Moderate and severe (GOLD II–IV)	45.2± 14.4	174 (96.1)	27.9 ± 5	46 (52%)	2.2 ± 1.3
Bouquet et al, 2020 (27)	130 (65)	65.5 (50–93)	Severe (FEV1<50%)	38 (13–85)	177 (88.5)	NR	NR	NR
Boutou et al, 2014 (18)	68 (51.5)	68 ± 8.8	NR	33.6 ± 14.7	NR	24 ± 6.3	NR	NR
Choi et al, 2018 (26)	78 (75)	73.0 ± 8.4	Severe	NR	79 (76)	NR	NR	NR
Eklöf et al, 2020 (15)	9868 (44.7)	69 (62–76)	NR	49 (36–63)	17.022 (77.2)	25 (21–29)	249 (1.1)	NR
Jacobs et al, 2020 (17)	NR	68 (61–74)	NR	49.4 ± 6.04	181 (100)	NR	17 (9.4)	4 (3–5)
Martínez-García et al, 2021 (10)	155 (91.2)	70.1 ± 9.1	Moderate and severe (GOLD II–IV)	50.1 ± 12	170 (100)	27.8 ± 4.8	107 (62.9)	2.2 ± 1.4
Rodrigo-Troyano et al, 2018 (19)	171 (83)	72.2 (8.5)	Severe (92% GOLD D)	35 (IQR 21)	78 (38)	26 (IQR 5)	NR	4 (IQR 3)

Notes: Values are mean ± SD or median (Interquartile range (IQR or Q1-Q3)), unless otherwise indicated. ^$Smokers include active and former smokers.

Abbreviations: BMI, Body Mass Index; FEV1, Forced expiratory volume in 1 second; IQR, interquartile range; GOLD, Global Initiative for Obstructive Lung Disease; NR, Not Reported.

Table 3 Summary of Results of Mortality in Patients with and without PA Isolation

Mortality
Study	Data	Follow Up
Almagro et al 2012 (16)	Adjusted mortality risk (HR 2.2, 95% CI: 1.2–4.2; p = 0.02)	3 years
Eklöf et al 2020 (15)	Adjusted mortality risk (HR 2.7, 95% CI: 2.3–3.4, p<0.001). Sensitivity analysis in bronchiectasis patients: HR 2.9 (95% CI: 2.4–3.5)	2 years
Jacobs et al 2020 (17)	Adjusted mortality risk (HR 1.78, 95% CI: 1.24–2.55, p=0.001) Sensitivity analysis adjusting for bronchiectasis: HR 1.89 (95% CI: 1.22–2.94; p = 0.005)	3 years
Martínez-García et al 2021 (10)	Adjusted mortality risk of a single PA isolation during follow-up vs no PA (HR 1.25, 95% CI: 0.79–1.97, p=0.34) Adjusted risk of mortality of persistent isolation of PA during follow-up vs single isolation event (HR 3.06, 95% CI: 1.8–5.2, p=0.001) Adjusted risk of mortality for the number of PA isolates (HR 1.2, 95% CI: 1.1–1.4, p<0.001)	84 months
Boutou et al 2014 (18)	Unadjusted mortality risk (HR 1.21, 95% CI: 0.70–2.10, log rank test p=0.49).	81.2 months
Rodrigo-Troyano et al 2018 (19)	Unadjusted mortality risk (HR 2.29, 95% CI: 0.74–7.12, p=0.15)	1 year

Abbreviations: HR, Hazard ratio; CI, Confidence interval; PA, Pseudomonas aeruginosa.

Figure 2 Forest plot of meta-analysis for death.

Table 4 Summary of Results of Hospitalisations and Exacerbations in Patients with and without PA Isolation

Time to Hospitalisation
Study	Data	Follow Up
Eklöf et al 2020 (15)	Adjusted risk of the composite outcome hospitalisation for COPD or all-cause death (HR 2.8, 2.2–3.6, p<0.001). Sensitivity analysis on bronchiectasis patients: HR 2.5 (95% CI: 1.9–3.3)	2 years
Rodrigo-Troyano et al 2018 (19)	Unadjusted Risk of readmission (HR 0.95, 0.53–1.68, p=0.85)	1 year
Risk of readmission
Choi et al 2018 (26)	Propensity score-adjusted readmission risk in patients PA positive vs no PA positive (OR= 3.60, 95% CI: 1.03–8.70, 23.1% vs 7.7%, p=0.030) Propensity score and covariables-Adjusted risk (OR= 4.75, 95% CI: 1.29–17.40)	30 days
Rodrigo-Troyano et al 2018 (19)	Unadjusted proportion of patients with one readmission in PA vs no-PA groups (79% vs 75%, p=0.9) Unadjusted number of patients with >3 readmissions (33% vs 11%, p=0.01. OR= 4.1, 95% CI: 1.3–12.8)	1 year
Number of readmissions
Almagro et al 2012 (16)	Unadjusted mean number of readmissions (1.3±1.5 vs 1.2 ±1.6, p=0.8).	1 year
Rodrigo-Troyano et al 2018 (19)	Unadjusted median number of readmissions/1000 follow-up days (2.7 vs 2.7, p=0.7)	1 year
Jacobs et al 2020 (17)	Unadjusted COPD-related hospitalisation rates per 100 persons-month (rate 1.87 (95% CI 1.22–2.74) vs 0.89 (95% CI 0.51–1.44), p=0.02). Unadjusted Rate ratio 1.15, 95% CI: 1.59–2.78	3 years
Martínez-García et al 2021 (10)	Unadjusted mean number of severe exacerbations (0.76 ± 1.0 vs 0.23 ± 0.4, p= 0.003)	84 months
COPD exacerbations
Bouquet et al 2020 (27)	Adjusted risk of an exacerbation event (OR 1.20, 95% CI: 1.03–1.39) Adjusted risk of frequent exacerbations (≥2/y) (OR 1.48, 95% CI: 1.31–1.68)	3 years
Jacobs et al 2020 (17)	Unadjusted exacerbation rates per 100 person-month (15.7 vs 7.5, p<0.001)	3 years
Martínez-García et al 2021 (10)	Unadjusted annual total exacerbation rates (1.87 ± 1.3 vs 0.84 ± 0.8, p= 0.009) annual moderate exacerbation rates (1.11 ± 1.3 vs 0.61 ± 0.9, p= 0.01)	84 months
Rodrigo-Troyano et al 2018 (19)	Unadjusted number of non-hospitalised exacerbations (1 vs 1, p=0.8)	1 year

Abbreviations: OR, Odds ratio; HR, Hazard ratio; CI, Confidence interval; PA, Pseudomonas aeruginosa.

Figure 3 Forest plot of meta-analysis for time to hospitalisation, risk of readmission and number of readmissions.