The impact of community-acquired pneumonia on the health-related quality-of-life in elderly
© The Author(s). 2017
Received: 12 October 2016
Accepted: 1 March 2017
Published: 14 March 2017
The sustained health-related quality-of-life of patients surviving community-acquired pneumonia has not been accurately quantified. The aim of the current study was to quantify differences in health-related quality-of-life of community-dwelling elderly with and without community-acquired pneumonia during a 12-month follow-up period.
In a matched cohort study design, nested in a prospective randomized double-blind placebo-controlled trial on the efficacy of the 13-valent pneumococcal vaccine in community-dwelling persons of ≥65 years, health-related quality-of-life was assessed in 562 subjects hospitalized with suspected community-acquired pneumonia (i.e. diseased cohort) and 1145 unaffected persons (i.e. non-diseased cohort) matched to pneumonia cases on age, sex, and health status (EQ-5D-3L-index). Health-related quality-of-life was determined 1–2 weeks after hospital discharge/inclusion and 1, 6 and 12 months thereafter, using Euroqol EQ-5D-3L and Short Form-36 Health survey questionnaires. One-year quality-adjusted life years (QALY) were estimated for both diseased and non-diseased cohorts. Separate analyses were performed for pneumonia cases with and without radiologically confirmed community-acquired pneumonia.
The one-year excess QALY loss attributed to community-acquired pneumonia was 0.13. Mortality in the post-discharge follow-up year was 8.4% in community-acquired pneumonia patients and 1.2% in non-diseased persons (p < 0.001). During follow-up health-related quality-of-life was persistently lower in community-acquired pneumonia patients, compared to non-diseased persons, but differences in health-related quality-of-life between radiologically confirmed and non-confirmed community-acquired pneumonia cases were not statistically significant.
Community-acquired pneumonia was associated with a six-fold increased mortality and 16% lower quality-of-life in the post-discharge year among patients surviving hospitalization for community-acquired pneumonia, compared to non-diseased persons.
KeywordsQuality-of-life Community-acquired pneumonia Elderly Follow-up Mortality
Community-acquired pneumonia (CAP) causes considerable disease and economic burden. In the Netherlands, the overall incidence of CAP was estimated to be 295 per 100,000 inhabitants, yielding approximately 50,000 episodes per year, with considerable variation between age-groups . Approximately 45% of all CAP episodes occur in persons aged ≥65 years . In the period after recovery, CAP is associated with higher risks on e.g. stroke and other cardiovascular events [2, 3]. Both CAP and the occurrence of these other diseases in the post-discharge period may impact on the health-related quality-of-life (HrQol). However, only limited data are available on HrQol after a CAP episode . In only two of six studies that focused on HrQol after CAP [5–10] patient follow-up exceeded 6 weeks. El Moussaoui et al.  followed patients for 18 months using the Short-Form (36) Health survey  (referred hereafter as SF36), and Honselmann et al.  determined the HrQol at one-year post-discharge using the Euroqol EQ-5D-3L instrument  (referred hereafter as EQ5D) in patients that had survived an episode of pneumonia and/or sepsis for which admission to intensive care was needed. These studies were all descriptive, and none of these studies quantified the excess quality-adjusted life-years (QALY) lost due to CAP in comparison with non-diseased persons (i.e. no pneumonia). The aim of the current study was to quantify differences in HrQol of community-dwelling elderly with and without CAP during a 12-month follow-up period. In addition, possible HrQol differences between radiologically confirmed and radiologically non-confirmed CAP cases were investigated.
Study design, setting and participants
Definitions of subgroups
Additionally, we did distinguish between “radiologically confirmed” CAP cases and the matched non-diseased subjects and “radiologically non-confirmed” CAP cases and their matched non-diseased subjects. A “radiologically confirmed” CAP was defined as the presence of two or more clinical signs of pneumonia together with a chest x-ray consistent with pneumonia, identical to the definition used within the CAPiTA-trial .
Date of birth, sex, place of residence, loss-to-follow-up due to death during the follow-up period and causes of death were extracted from the CAPiTA-study files . Health status (EQ5D) and socio-demographic status (living situation and education) were collected at the time of vaccination with the CHO-CAP-baseline questionnaire. Full details of data collection of nested matched-cohort study are provided in Mangen et al. . In short, comorbidity details were collected during the home visit. Current living situation was collected at all four contact moments. Health status (EQ5D) was collected thrice for suspected pneumonia cases during the home-visit interview, reflecting health status (1) at day of interview, (2) at the worst moment during the recent pneumonia episode, and (3) previous to the recent pneumonia episode. Health status was also collected at month 1, month 6 and month 12 after initial visit using both EQ5D and SF-36. For non-diseased subjects, both EQ5D and SF-36 were administered at all four contact moments. For suspected pneumonia cases, clinical information on hospital admission (e.g. X-ray result; clinical symptoms; length of stay) was extracted from the CAPiTA-study files .
Health status questionnaires
The SF-36 is composed of 36-items measuring health across eight domains (physical functioning, social functioning, role limitations with respect to physical activities, role limitations with respect to emotional activities, pain, mental health, vitality and general health perception). Responses to each item within a domain are combined to generate a score from 0 to 100, where 100 indicates best health . Because of the elderly population - some potentially in poor health - the usual order of items in question 3 was inversed . Applying the scoring-method developed by Brazier et al. , we further derived the SF-6D health-index from the SF-36 survey, a numerical index between 0 (“death”) and 1 (“full health”) . The EQ5D consists of two parts, the EQ-5D-descriptive system and the EQ-visual analogue scale (VAS) . The EQ-VAS records the participants’ self-reported health on a VAS from 0 (“Worst imaginable health state”) to 100 (“Best imaginable health state”) . The EQ5D-descriptive system consists of five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and three functioning levels (no problems, some problems or severe problems) [12, 18]. The EQ5D health states were scored with the Dutch value-set , to obtain EQ-5D-3L summary indexes (EQ-index) ranging from 0 (“death”) to 1 (“full health”) [12, 19].
Quality Adjusted Life Years (QALY) is a concept used to reflect a year in full quality of life. Hence, QALYs combine both length of life and quality of life. Quality of life is represented in a value between 0 (death) and 1 (optimal quality of life). QALYs are estimated by multiplying length of life with the indicator value for quality of life. One-year QALY estimates, with and without pneumonia episode included, were calculated for both cohorts, using the self-reported EQ5D health states and its associated index values at the different contact moments based on recorded date of contact moment. An area under the curve approach was followed by interpolating between the observations provided by the patients. For patients who died, we calculated QALY by using the date of death and a utility score of 0 from that date onwards. For missing EQ-indexes, ten imputations were performed. QALYs were calculated in each imputed dataset and averaged over the ten imputated datasets. The observed utility difference between both cohorts was attributed to the CAP episode. Excess QALY loss was calculated for the one-year post-discharge period, excluding and including the CAP episode, respectively (see Additional file 1: Figure S1A for illustration). Additionally, we estimated the QALY and the excess QALY loss for one-year survivors. Pairs of pneumonia cases and non-diseased subjects in which one of the three died during the follow-up were excluded from these estimates.
Health status and QALY estimates in the suspected pneumonia cases and non-diseased subjects are presented for the different follow-up moments, in a decomposed manner (i.e. at the level of the different domains of quality of life) and as summary index. Causes of death were categorized into five categories: (1) infectious diseases; (2) chronic lung diseases; (3) cancer; (4) cardiovascular events and stroke and (5) others. Depending on the nature and distribution of data, we used Chi-square test for categorical variables (e.g. sex, education) and non-parametric tests for non-normally distributed variables (e.g. scores) to test for differences between both cohorts (i.e. diseased and non-diseased cohort) and for differences between patients with and without confirmed CAP. Correlation between the different instruments was studied using Spearman’s rank correlation coefficient. All analyses were performed using IBM SPSS Statistics version 21.
Of the 3225 identified suspected pneumonia episodes in the CAPiTA-trial, 1750 (54%) belonged to the CHO-CAP source population, of which 562 (32%) participated; 341 (61%) had radiologically confirmed CAP and 221 (39%) had radiologically non-confirmed CAP (Fig. 1). Reasons for non-participation/exclusion are provided in in the Additional file 1: Table S1A.
Suspected pneumonia cases
Baseline characteristics of suspected pneumonia cases and their non-diseased subjects
Suspected pneumonia cases (i.e. “diseased” cohortb)
Male, in %
Age at inclusiona, median (IQR)
EQ5D-index (at vaccination), median (IQR)
Number of self-reported comorbidities at inclusiona, median (IQR)
Educational level, in %
Region, in %
Living situation at vaccination, in %
Two or more person/household
Vaccinated, in %
Compared to the non-diseased subjects, suspected pneumonia cases more frequently died during the one-year follow-up period (8.4% vs 1.2%;p < 0.001 (in the Additional file 1: Figure S2A.); attributable risk:0.059(95% CI:0.058–0.060)) or withdrew from the study (16.7% vs 9.9%; p < 0.001), mainly because of bad health (in the Additional file 1: Table S2A). Chronic lung diseases, cardiovascular events and stroke were more frequently reported as being the cause of death for suspected pneumonia cases than for non-diseased subjects (p = 0.054; in the Additional file 1: Table S2A)).
EQ5D-index, EQ-VAS and SF6D-index for suspected pneumonia and the non-diseased subjects
Suspected pneumonia cases
Mean (SD)/Median (IQR)
Mean (SD)/Median (IQR)
0.87 (0.16)/0.89 (0.78–1.00)
0.87 (0.16)/0.89 (0.78–1.00)
Prior to illness onset
0.81 (0.23)/0.86 (0.78–1.00)
0.23 (0.32)/0.24 (−0.00–0.43)
During home visit
0.70 (0.26)/0.78 (0.52–0.89)
0.84 (0.18)/0.84 (0.78–1.00)
0.72 (0.24)/0.78 (0.65–0.89)
0.83 (0.17)/0.84 (0.78–1.00)
0.74 (0.23)/0.78 (0.66–0.89)
0.82 (0.18)/0.84 (0.78–1.00)
0.74 (0.23)/0.78 (0.67–0.89)
0.82 (0.18)/0.84 (0.78–1.00)
Prior to illness onset
71 (15.3)/70 (60–80)
33 (16.0)/30 (20–41)
During home visit
62 (16.7)/65 (50–70)
76 (13.2)/80 (70–85)
64 (16.3)/65 (50–75)
76 (13.9)/79 (70–85)
65 (16.4)/70 (55–78)
74 (15.2)/75 (65–84)
64 (17.5)/69 (50–78)
75 (14.6)/75 (68–85)
During home visit
0.77 (0.13)/0.79 (0.66–0.88)
0.65 (0.13)/0.63 (0.58–0.73)
0.76 (0.13)/0.77 (0.65–0.88)
0.68 (0.14)/0.66 (0.59–0.79)
0.75 (0.14)/0.75 (0.63–0.88)
0.68 (0.14)/0.66 (0.58–0.77)
0.75 (0.13)/0.75 (0.63–0.87)
Utility difference attributable to suspected pneumonia
suspected pneumonia case
Utility difference attributable to suspected pneumonia
Pneumonia episode & one-year post-discharge
Pneumonia episode & one-year post-discharge
EQ5D-index, EQ-VAS and SF6D-index were positively correlated at all contact moments for suspected pneumonia cases and non-diseased subjects (rho > 0.45), in the Additional file 1: Table S3A and Table S4A. The highest correlation was found between EQ5D-index and SF6D-index for both suspected pneumonia cases and non-diseased subjects (rho >0.67 for all contact moments).
Radiologically confirmed and non-confirmed CAP cases
Clinical data of radiologically confirmed and radiologically non-confirmed CAP cases
Radiologically confirmed CAP cases
Radiologically non-confirmed CAP cases
Positive chest X-ray, in %
Number of clinical criteria, median (IQR)
PSI score, median (IQR)
Admitted to ICU, in %
Readmitted within 30 days, in %
LOS in days, median (IQR)
At 1st admission,
In immunocompetent elderly, hospitalization for suspected pneumonia was associated with a six-fold higher risk of mortality and an average loss of QALYs attributable to pneumonia of 0.13 after 1 year, compared to non-diseased subjects. Patients with radiologically confirmed CAP had a two-fold higher mortality risk than those with radiologically non-confirmed CAP, but the average loss of QALYs attributable to CAP among survivors was comparable. The one-year QALY loss associated with a CAP episode (0.13, excluding the CAP episode, and 0.15, including the CAP episode) is two-fold higher than the QALY loss that we used  in a cost-effectiveness analysis of pneumococcal vaccination (0.071) and is more than tenfold higher than the QALY loss used by Melegaro and Emunds  in 2004 and in most cost-effectiveness studies conducted thereafter in Western European countries (e.g. [23–26]), namely 0.004 for inpatient CAP and 0.0079 for bacteraemia. These estimates of QALY loss were based on expert opinion and not real-life data. Preventing a higher QALY loss through pneumococcal vaccination by definition contributes to more favourable cost-effectiveness of vaccination. For example using a QALY loss of 0.15 rather than 0.07 would have resulted in a somewhat more favourable incremental cost-effectiveness ratio of 8,200 €/QALY versus the 8,650 €/QALY presented in our recently published cost-effectiveness analysis . Although the difference in QALYs is relatively large, the impact on the cost-effectiveness ratio is relatively limited, as mortality has a much higher impact on the cost per QALY gained than quality-of-life.
Strengths of this study include the rigid prospective study design nested within a randomized double-blinded placebo-controlled trial that created the possibility to quantify the excess QALY lost due to CAP in community-dwelling elderly using a one-year follow-up period. We also conducted separate analyses for patients with radiographically confirmed CAP and those without confirmation.
To control for potential biases between pneumonia cases and non-diseased subjects, subjects in both cohorts were matched on age, sex and EQ5D-index as collected at the time of vaccination. CAP patients had slightly more comorbidities and a lower educational level, factors known to be negatively associated with health status [27–29]. The calculated excess QALY loss might therefore be a slight overestimation of the attributable QALY loss. Furthermore, our study may have suffered from a healthy participant effect, as the study population consisted of subjects that were willing-to-participate in a one-year follow-up study who may have been healthier than the non-responding CAP patients. Indeed, one of the major arguments to refuse participation was self-perceived bad health, and patients with a recent cancer diagnosis were excluded as well. In a sicker population, mortality attributable to CAP would most likely have been higher. As a result, the observed QALY loss attributable to CAP and the mortality risk within the first year post-discharge may have been underestimated.
The current study is the first that provides detailed HrQol during the recovery process of hospitalized elderly suspected pneumonia patients for a one-year post-discharge period using the EQ5D and SF36 questionnaires. It further provides a QALY loss attributable to CAP for community-dwelling elderly, which is a necessity for economic analyses targeted at preventing pneumonia infections and as such contributes to more realistic future estimates of cost-effectiveness of preventive interventions for this infection. The CAP episode is the onset of sustained loss of quality-of-life, with an estimated difference in QALY of 16–18% between CAP patients and their non-diseased subjects.
Due to logistical reasons the first 14.7% of CAPiTA-participants were not invited to participate in the CHO-CAP-study.
48,634 participants returned the questionnaire with signed informed consent. For 47,476 participants (97%) an EQ5D-score could be estimated.
Community-acquired pneumonia immunization trial in adults
Costs, health status and outcomes of CAP (Community-Acquired Pneumonia) - study
Euroqol EQ-5D-3L instrument
Quality-adjusted life years
Short form-36 health survey questionnaire
Euroqol visual analogue scale
The authors would like to thank all “Costs, Health status and Outcomes of community-acquired pneumonia (CAP)” (CHO-CAP) participants for their participation. The “Community-Acquired Pneumonia immunization Trial in Adults” (CAPiTA) team and the CHO-CAP-team from Julius Clinical B.V. in Zeist are acknowledged for their logistic support during the data collection. The CHO-CAP study is made possible by an unrestricted grant from Wyeth Pharmaceuticals, which was acquired by Pfizer Inc. in October 2009, to the University Medical Centre Utrecht.
The CHO-CAP study is made possible by an unrestricted grant from Wyeth Pharmaceuticals, which was acquired by Pfizer Inc. in October 2009, to the University of Medical Centre of Utrecht.
Availability of data and materials
The datasets analysed during the current study is available from the corresponding author on reasonable request.
Study concept and design: M-JJM, MJMB, GAdW. Acquisition, analysis, or interpretation of data: M-JJM, SMH, MJMB, GAdW. Drafting of the manuscript: M-JJM. Critical revision of the manuscript for important intellectual content: All authors. Study supervision: MJMB and GAdW. All authors read and approved the final manuscript.
Bonten reports receipt of research funding from Pfizer, and service on the CAPiTA European Expert Meeting. Huijts reports receipt of financial support for printing her PhD thesis from Pfizer. De Wit reports receipt of unrestricted research grant from Pfizer paid to UMCU. Huijts and Mangen’s research funding is partially supported by these grants provided to UMCU by Pfizer. Bonten, Huijts, Mangen, and de Wit are UMCU employees. No other disclosures were reported.
Consent for publication
Ethics approval and consent to participate
Approval was granted by the Central Committee on Research involving Human Subjects (Ref: NL.24770.041.08). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Role of the sponsor
Pfizer Inc. had no role in the design, analysis, interpretation of the data, or the writing of the manuscript. Pfizer Inc. did review a penultimate version of the manuscript.
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