Patient Preferences in empYema treatment (PAPY-study): are we investigating relevant outcomes for patients?
Weija R. de Jonge1,2
, Josje Altenburg2,3, Chris Dickhoff1,3
, Martijn van Dorp1,3
, Jouke T. Annema2,3, David J. Heineman1,3
Abstract: Parapneumonic pleural infection is a common clinical issue and limited data are available regarding patients’ treatment preferences and the extent to which these preferences influence treatment decision-making. This study aimed to identify outcome measures that are most relevant for patients who underwent treatment for parapneumonic pleural infection. Data were collected through a questionnaire on treatment experiences and preferences, complemented by a structured interview. Between 2021 and 2023, patients treated at a single tertiary referral center were identified. Eligible patients had undergone either chest tube drainage (with or without intrapleural enzymatic therapy, IET) or surgery (open thoracotomy or video-assisted thoracoscopic surgery, VATS). A total of twelve patients met the inclusion criteria. Four were treated with a chest tube (with or without IET), and eight underwent surgical intervention, including those who initially received drainage but subsequently required surgery. Despite the small sample size, several consistent themes emerged. Pain and immobilization were identified as key patient-reported outcome measures of hospitalization and treatment. Furthermore, minimizing the risk of complications and reducing the duration of antibiotic treatment were identified as key treatment priorities. Following treatment, full recovery, returning to work, and performing daily activities were crucial outcomes for patients. This study identifies the patient-reported outcome measures most important to patients and highlights the need to incorporate them into future clinical research on parapneumonic pleural infection.
Keywords: Empyema; patient-reported outcome measures (PROMs); pleural infections
Submitted May 09, 2025. Accepted for publication Aug 01, 2025. Published online Sep 26, 2025.
doi: 10.21037/jtd-2025-924
Introduction
The incidence of parapneumonic pleural infection, including complicated parapneumonic effusion (CPPE) and empyema, is increasing worldwide (1-4). The mortality rate is approximately 20% within the first year, rising to 35% in frail patients (5-8). Parapneumonic pleural infection is defined as the presence and replication of bacteria in the pleural space, most commonly resulting from bacterial translocation from an infected lung (5,9).
The optimal treatment regimen for parapneumonic pleural infections remains a topic of debate. At time of suspected diagnosis, current guidelines recommend prompt initiation of antibiotic treatment, a thoracentesis to obtain a culture, and adequate drainage of the infected fluid from the pleural space (5,8,10). Adequate drainage of the infected fluid can be achieved by either a chest tube [with or without the use of intrapleural enzymatic therapy (IET)] or surgery [video-assisted thoracoscopic surgery (VATS) or thoracotomy] (11).
To investigate the efficacy of therapy, previous studies on the treatment of parapneumonic pleural infections selected outcome measures such as length of hospital stay (LOS), mortality, morbidity, need for additional interventions, and costs (12-15), and compared these between surgical and non-surgical treatments. However, from a patient’s perspective, when selecting the optimal treatment, other outcome measures may also be important, such as quality of life (QoL), pain scores, and return to work (16-19). This study investigates which outcome measures are relevant for patients who were treated for a parapneumonic pleural infection by gathering information through a questionnaire regarding their experiences and preferences, complemented by a structured interview. We present this article in accordance with the COREQ reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-924/rc).
Methods
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional Medical Ethics Committee of the Amsterdam UMC (2023.0138) and all patients provided written informed consent.
An electronic search was conducted to identify patients treated for parapneumonic pleural infection at our hospital (Amsterdam UMC) between 2021 and 2023. Included were Dutch-speaking patients aged 18 years or older; treated for parapneumonic pleural infection/empyema either with a chest tube (with or without IET) or surgery (VATS or open surgery). Excluded were patients under 18 years of age; patients with cognitive deficits or other cognitive impairments affecting their ability to read and understand the Dutch language; patients who had died; patients who were not treated with one of the above-mentioned treatment options; patients with a chronic parapneumonic pleural infection; or those with a parapneumonic pleural infection caused by factors other than pneumonia (e.g., post-surgery or tuberculosis). Patients who developed complications due to their past medical history were also excluded, to prevent outcomes being potentially influenced by factors other than parapneumonic pleural infection and its subsequent treatment.
Eligible patients were invited to participate via a phone call from the treating cardiothoracic surgeon or pulmonologist. If consent for participation was obtained, an information letter and consent form, along with a questionnaire, were sent by mail, after which the completed questionnaire and signed consent form had to be returned to the hospital. The questionnaire consisted of questions regarding the patients’ experiences in the hospital, their treatment, their preferences, and patient-reported outcome measures (PROMs). Additionally, there was an option for free-text responses on experiences and preferences, allowing respondents to express their genuine opinions rather than choosing from a set of predetermined responses. The questionnaire sent can be found in the supplementary file (Appendix 1). In addition to the questionnaire, the same patients participated in a one-time structured interview conducted via an online meeting to provide more detailed insights into their experiences. The interview was conducted by three of the authors: one master’s student in Medicine (W.R.d.J.) and two medical doctors with a PhD (J.A. and D.J.H.).
This study aimed to identify specific outcomes that are important to patients regarding their treatment, and to utilize this information in future trial designs focusing on this complex and widespread clinical problem. Our primary outcome was the patients’ experiences with their treatment for parapneumonic pleural infections in terms of PROMs. A comparison was made between the different treatment options based on the outcomes of the questionnaires. Secondly, we examined clinical details from the hospital admission, such as LOS, complications, chest tube duration, type and duration of IET, lab values, and the duration of antibiotic treatment.
Results were analyzed after receiving the completed questionnaires using descriptive statistics, and demographic and clinical data related to the course of the disease and treatment were extracted from the electronic patient records. A coded sheet for collecting patient information was used to ensure the privacy of the patients, concealed in accordance with Good Clinical Practice guidelines. Access to this sheet was restricted to the first and last author only (W.R.d.J. and D.J.H.). For continuous outcome measures, we reported means with standard deviation (SD), and for dichotomous data, we reported proportions. For frequencies, distributions were used to assess the number of participants selecting each of the pre-determined responses.
Results
Between 2021 and 2023, 23 patients with parapneumonic pleural infection treated at Amsterdam UMC met the inclusion criteria. After approaching these patients, 19 consented to receive the questionnaire, of which 12 were fully completed and returned, yielding a 63% response rate. A distinction was made between two groups: the conservative group (n=4), consisting of patients solely treated with a chest tube with or without the use of IET, and the surgical group (n=8), consisting of patients treated with VATS or thoracotomy, with or without a chest tube prior to surgery (with or without IET). In the surgical group seven patients had been treated previously with a chest tube, with or without IET (see Figure 1 for a flowchart of patients and treatments). The sociodemographic and clinical characteristics of the patients are summarized in Table 1. Patients treated with VATS had a mean ASA score of 2 or 3. Out of the 8 surgical patients, 7 patients received a postoperative ultrasound guided erector spinae block from the anesthetist. Among patients who received IET, there was considerable variation in the medication used (urokinase, alteplase, or a combination of alteplase and dornase), as well as in the number of times that IET was administered through the chest tube (mean: 4 times; range, 1–6). In one patient, IET was discontinued due to suspected bronchopleural fistula, despite the absence of radiographic evidence. The mean total LOS was 15 days for all patients, with 13 days in the conservative group versus 17 days in the surgical group (including the days preceding the surgical interventions). Complications were only reported in the surgical group and were classified according to the Clavien-Dindo classification (20). The reported complications included a hemothorax after VATS requiring reintervention with thoracotomy (grade IIIb), persistent pleural collection requiring repeat chest tube insertion (grade IIIa), thrombophlebitis treated with antibiotics (grade II), atrial fibrillation requiring pharmacological treatment (grade II), wound infection (grade I), and acute kidney injury/transient elevation of serum creatinine (grade I). The mean total duration of antibiotic treatment was 34 days (range, 13–55 days). In some patients, antibiotics were initiated prior to hospital admission and intervention and continued after discharge.
Table 1
| Variables | Overall (n=12) | Treatment group | |
|---|---|---|---|
| Conservative (n=4) | Surgical (n=8) | ||
| Age (years) | 63±18 [30–89] | 72±13 [59–89] | 59±19 [30–79] |
| Gender (male, %) | 8 (66.7) | 2 (50.0) | 6 (75.0) |
| Comorbidities† | 8 | 5 | 3 |
| Respiratory disease | 1 | 1 | 0 |
| DM type 2 | 2 | 2 | 0 |
| Cardiovascular disease | 2 | 1 | 1 |
| HIV | 1 | 1 | 0 |
| Oncological history | 2 | 0 | 2 |
| Symptoms‡ | |||
| Chest pain | 8 | 3 | 5 |
| Cough | 6 | 2 | 4 |
| Weakness | 5 | 2 | 3 |
| Dyspnea | 4 | 1 | 3 |
| Illness days before hospital admission | 9±5 [2–14] | 9±5 [5–14] | 9±5 [2–14] |
| Leukocytes day 0 (×109/L) | 17.8±8.6 [6.6–39.9] | 13.9±1.2 [12.7–15.5] | 19.8±10.2 [6.6–39.9] |
| CRP day 0 (mg/L) | 339±145 [36–564] | 199±153 [36–389] | 409±78 [318–564] |
| Pleural fluid analysis | |||
| Germ identification | 41.7% | 50% | 37.5% |
| Streptococcus pneumoniae | 16.7% | 0% | 25% |
| Streptococcus anginosus | 16.7% | 50% | 0% |
| Slackia exigua | 8.3% | 0% | 12.5% |
| Length of hospital stay (days) | 15±7 [6–26] | 13±8 [6–22] | 17±8 [6–26] |
| Total duration of chest tube (days) | 9±5 [3–18] | 8±4 [5–13] | 10±6 [3–18] |
| Complications§ | 6 (50.0) | 0 (0.0) | 6 (75.0) |
| Minor§ | 4 (33.3) | 0 (0.0) | 4 (50.0) |
| Major§ | 2 (16.7) | 0 (0.0) | 2 (25.0) |
| Number of days of antibiotics | 34±13 [13–55] | 34±17 [14–50] | 34±13 [13–55] |
| Number of days of antibiotics after first intervention | 30±13 [9–48] | 30±16 [9–47] | 30±12 [11–48] |
Data are presented as mean ± standard deviation [range] or n (%) or n. †, some patients had more than one comorbidity; ‡, some patients had more than one symptom; §, complications according to the Clavien-Dindo classification: minor complications, grade I–II; major complications, grade III–V. Some patients had more than one complication. CRP, C-reactive protein; DM, diabetes mellitus; HIV, human immunodeficiency virus.
Tables 2,3 present the questionnaire results. For patients treated conservatively, pain was the most important complaint during hospitalization, followed by immobilization. In surgically treated patients, immobilization was the primary complaint during hospitalization, followed by pain and the duration of the hospital admission. When asked what they would like to see improved if they had to receive the same treatment a second time, minimizing the risk of complications and reducing the duration of antibiotic treatment were the most important items. Patients were also asked whether they had a choice regarding their treatment; however, none reported having the option to choose between treatments. In most cases, they followed the physician’s recommendation. In other cases, they were either deemed unfit for surgery or surgery was considered inevitable due to a declining clinical condition in which IET was considered inappropriate. After discharge, patients in both groups needed a mean of 7 weeks to resume daily activities and 12 weeks to return to work.
Table 2
| Question | Total (N=12) | Treatment group | |
|---|---|---|---|
| Conservative (N=4) | Surgical (N=8) | ||
| Time it took to do your daily activities after discharge (weeks), mean | 7 | 9 | 6 |
| Time it took to start working again after discharge (weeks), mean | 12 | 12 | 12 |
| Pain during the hospital admission, mean ± SD [range]† | 6.1±2.7 [1–10] | 7.8±1.5 [7–10] | 5.3±2.9 [1–9] |
| Dyspnea during the hospital admission, mean ± SD [range]† | 6.3±2.8 [1–10] | 6.5±3.9 [1–10] | 6.3±2.4 [2–9] |
| Fear during the hospital admission, mean ± SD [range]† | 5.0±2.8 [0–10] | 4.8±4.3 [0–10] | 5.1±2.2 [2–8] |
| What was unpleasant about the treatment with a chest tube?‡ (number of times mentioned) | |||
| Pain | 9 | ||
| Dyspnea | 2 | ||
| Duration of the hospital admission | 1 | ||
| Immobilization | 7 | ||
| What was unpleasant about the treatment with a surgery?‡ (number of times mentioned) | |||
| Pain | 4 | ||
| Dyspnea | 1 | ||
| Duration of the hospital admission | 1 | ||
| Immobilization | 6 | ||
| What would you like to be different if you had this treatment again?‡ (number of times mentioned) | |||
| More information about the treatment options | 3 | ||
| Shorter length of hospital stay | 1 | ||
| Shorter duration of antibiotic treatment | 4 | ||
| Shorter duration of chest tubes in situ | 2 | ||
| Minimizing risk of a complication | 8 | ||
| Better evaluation of side effects | 1 | ||
†, ranges from 0 (no complaints) to 10 (many complaints); ‡, multiple answers were possible. SD, standard deviation.
Table 3
| Most frequent | Complaint |
|---|---|
| 1 | Pain |
| 2 | The duration of the chest tubes in situ |
| 3 | Long-term use of antibiotics |
| 4 | Dyspnea |
| 5 | Long hospital stay |
“Most frequent” indicates the frequency of each complaint, with 1 being the most reported.
Results from a structured patient interview revealed that patients initially experience a watchful waiting approach without major interventions, leading to a prolonged LOS. The most important outcome measures identified by patients were full recovery, returning to work, and performing daily activities. Another key patient-reported outcome was the pain experienced during chest tube insertion. Additionally, side effects and the duration of antibiotic treatment and persistent post-operative pain were significant concerns for patients.
Discussion
In this small cohort study, we investigated patient preferences. A total of 12 patients treated for parapneumonic pleural infections completed a questionnaire about their experiences during hospital admission and recovery. Despite the small sample size, pain, especially during chest tube insertion, and immobilization emerged as the most unpleasant experiences of hospitalization and treatment. Additionally, minimizing the risk of complications and reducing the duration of antibiotic treatment were identified to be the most important priorities. Following treatment, full recovery, returning to work, and performing daily activities were highlighted as key outcome measures.
This is one of the first studies to report on patient preferences in individuals treated for parapneumonic pleural infections. A previous study investigated PROMs across various pleural diseases; however, only a small proportion of the included patients (2%) had a parapneumonic pleural infection (21). Another recent study assessing QoL using the 36-item Short Form Survey Instrument (SF-36), found that surgical patients reported greater pain but improved physical functioning compared to those managed with IET (18). Therefore, despite the small cohort size, the findings of this study should be considered in future research on parapneumonic pleural infections.
Pain is a significant concern for patients with parapneumonic pleural infections, regardless of whether they are managed conservatively or surgically. Surgical patients typically received postoperative erector spinae nerve blocks, which may account for the lower frequency of pain-related complaints observed in this group compared to those managed conservatively. In a study conducted by Ismail et al. (22), pain scores and analgesic use in patients undergoing VATS for pleural empyema were documented. Analgesics were administered for an average duration of four days, with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) being the most commonly used, suggesting that patients can be comfortable by using oral analgesics only. These findings highlight the importance of optimizing pain management strategies for all patients treated for parapneumonic pleural infection, given that pain is frequently reported and often considered the most burdensome symptom. Effective pain control may facilitate early mobilization, improve mucus clearance, and reduce the risk of secondary pulmonary infections, thereby offering potential benefits across all patient groups (23).
Nearly all patients experienced a period of immobilization, potentially resulting from prolonged chest tube drainage, which was consistently reported as one of the most unpleasant aspects of parapneumonic pleural infection management. Other studies have not adequately explored the impact of immobilization, underscoring a notable gap in the existing literature. Consequently, immobilization should be recognized as a significant PROM in future research. Immobilization and pain are two important factors that are taken into account in the Enhanced Recovery After Thoracic Surgery (ERATS) protocol. There is increasing evidence that an ERATS protocol will reduce length of stay and postoperative morbidity. However, patients with a parapneumonic pleural infection are in general more ill than the general population receiving thoracic surgery, making it harder to follow all the steps of such a protocol (24).
A notable finding in our study is the time required for patients to return to work, which was 12 weeks in both treatment groups. The time to resume daily activities ranged from 6 to 9 weeks in our cohort, depending on whether patients received conservative or surgical treatment. A study comparing return to work in surgically treated patients (undergoing VATS or thoracotomy) for empyema found that patients treated with VATS returned to work significantly earlier than those treated with thoracotomy (19). Another study researching VATS in elderly patients with pleural empyema, reported that 90% of the patients resumed normal activities of daily living within 30 days (25), a timeframe shorter than that observed in our cohort. This difference may be explained by variations in healthcare systems, access to rehabilitation, and social support systems between countries, all of which can influence recovery times. A randomized feasibility study assessed overall health at 2 weeks and 2 months after intervention (16), reporting better overall health of patients treated conservatively compared to those undergoing surgery.
The American Association for Thoracic Surgery recommends a minimum of 2 weeks of antibiotic treatment for pleural empyema (26). Two small, randomized trials evaluated short antibiotic courses (2 or 3 weeks) and reported that this was as effective as a longer course of antibiotics (27,28). The average treatment time with antibiotics in this study was 34 days, and the duration and side effects of antibiotic treatment were reported to be unpleasant by the respondents. A study from Avner et al. shows that routine use of antibiotics is indicated in the treatment of pleural empyema (29) but doubts the benefits of extended intravenous treatment with antibiotics compared to oral antibiotic treatment. Therefore, future research to antibiotic treatment in patients with a parapneumonic pleural infection should be a topic of interest.
Complications were most common after surgery. One patient needed a reintervention after a hemothorax. This is a rare complication after a VATS but can occur in 1–2% after general lung surgery (30). Bleeding after IET treatment is also a known complication (31); however, this complication was not reported in our small cohort.
Fortunately, PROMS are receiving more attention in ongoing randomized controlled trials on parapneumonic pleural infections. The FIVERVATS trial will assess the European Quality of life-5 Dimensions (EQ5D) and St. George Respiratory Questionnaire (SGRQ) with a 12-month follow-up (32). The DICE trial will utilize the World Health Organization Disability Assessment Schedule (WHODAS) with a follow-up of 6 weeks (33).
This study has several limitations. It involves a small, heterogeneous (especially type of IET) single-center cohort of 12 patients, excluding those with major comorbidities that could have influenced treatment perception and preferences on the treatment of pleural infection. However, results of this study might provide guidance for future research on this topic, with regard to choosing patient relevant outcome measures, choosing the correct questionnaires etc. Due to the retrospective design, selection bias may have occurred between conservatively and surgically treated patients, reflected in the older age and higher comorbidity burden in the conservative group. And the high crossover rate to the surgical group (see Figure 1) suggests more severe infections in those patients. In one case, surgical treatment was the only feasible option, further indicating disease severity in this cohort. Additionally, not all questionnaire items were completed, and some clinical data were missing due to patient transfers and incomplete hospital records. Furthermore, diagnostic parameters like pleural fluid pH values were only available in half of the cases, despite current guidelines recommending pH measurement as an essential diagnostic criterion for parapneumonic pleural infection (5). The reported pH values ranged from 6.9 to 7.5, indicating that not all patients fulfilled the diagnostic threshold (with pH ≤7.2 suggesting a high risk, and pH ≥7.4 a low risk of parapneumonic pleural infection). Due to the combination of the small sample size (n=12) and these limitations, it was not possible to differentiate between treatment modalities across all outcomes, nor to draw definitive conclusions regarding patient preferences for the various treatment strategies in parapneumonic pleural infection. Lastly, the results may underestimate the actual patient experience. The reported duration until resumption of daily activities or return to work were based on pre-defined answer categories, which may not accurately reflect individual variations. Additionally, self-reported measures such as pain, dyspnea, and anxiety may have been underreported. As all patients were treated within the past 2 years, recall bias remains a concern due to the time elapsed between treatment and completion of the questionnaire.
Despite the small sample size, pain and immobilization are mentioned as key outcome measures that should be considered in future research. Additionally, post-hospitalization priorities, such as resuming daily activities and returning to work, are crucial PROMs for patients and should be integrated into future studies.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the COREQ reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-924/rc
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-924/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-924/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional Medical Ethics Committee of the Amsterdam UMC (2023.0138) and all patients provided written informed consent.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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