Investigation of the Prevalence of Chronic Pulmonary Effusion Causes and Response to Treatment (Pleurodesis) in Patients

1. INTRODUCTION

The pleural space, which develops between the fourth and seventh week of embryonic development [1], plays a crucial role in pleural space homeostasis. The visceral and parietal pleura, originating from the lateral plane mesoderm, are essential components of this space [2]. Derived from embryonic mesoderm, the pleural mesothelium comprises a layer of mesothelial cells that envelop the chest wall and lungs at the parietal and visceral levels. In terms of cytological characteristics, these cells resemble mesothelial cells that cover other body cavities, such as the peritoneum [3,4].

Pleural effusion, arising from altered fluid production, absorption, or a combination of these factors, affects over 1.5 million patients annually in the United States. Key causes include heart failure, pneumonia, and cancer. It becomes clinically evident once fluid exceeds lymphatic absorption capacity [4]. While vital, the pleural space remains an area of ongoing research and debate [5]. Excess fluid accumulation in the pleural space can result from various benign or malignant causes [6]. Specifically, Malignant Pleural Effusion (MPE) denotes effusion marked by the presence of malignant cells. MPE is a common manifestation in patients with metastatic disease, affecting up to 15% of individuals with cancer [7]. It is predominantly associated with lung cancer, followed by breast cancer, lymphoma, gynecological cancers, and malignant mesothelioma. Annually, approximately 150,000 new cases of MPE are diagnosed in the United States, with an additional 100,000 cases in Europe [8]. The overall survival rate for patients with MPE ranges from 3 to 12 months after diagnosis, and common symptoms include shortness of breath, cough, and chest pain [9].

Managing MPE remains challenging due to the paucity of high-quality evidence and heterogeneity in clinical presentations worldwide. Between 30% and 50% of patients with metastatic malignancies show pleural involvement at autopsy, with pleural effusions of varying sizes observed in approximately half of these cases [10]. Despite the global burden of pleural effusion, current knowledge about its etiologies and clinical characteristics is insufficient, particularly in regions with limited research infrastructure [11]. This lack of data limits our ability to develop context-specific diagnostic and therapeutic strategies.

The geographical variation in causes and outcomes of pleural effusion underscores the need for region-specific studies. Understanding the unique epidemiological and clinical patterns in under-researched areas like ours can inform tailored management approaches and enhance global knowledge. Therefore, this study aims to investigate pleural effusion associated with malignancy among patients referred to Shahid Madani Medical Education Center during 2017–2018. By addressing the scarcity of data in this geographical region, we hope to bridge critical knowledge gaps and provide insights that can guide clinical practice and future research.

2. MATERIALS AND METHODS

The present study was conducted cross-sectionally. All patients referred with pleural effusion to educational centers from April 2019 to March 2021 were included in the study based on the inclusion and exclusion criteria.

2.8. Data Analysis Method

Sample size estimation was based on similar studies, with consideration for a 95% confidence level, 0.05 error coefficient, and 80% power. The sample size of 150 individuals was calculated using the following formula (43), taking into account the standard variation rate (a/2), standard deviation (σ), and desired error (d).

We analyzed the obtained data using SPSS software. SPSS software version 22 was used. Chi-score and one-way ANOVA statistical tests were used and a p-value less than 5% was considered significant. The results were presented as a mean and standard interval.

This study was approved by the Research Ethics Board of Alborz University of Medical Sciences (IR.ABZUMS.REC.1399.276).

The methods are stated by STROCSS guidelines. STROCSS (Strengthening the Reporting of Cohort Studies in Surgery) is a set of guidelines specifically developed to enhance the reporting quality and transparency of cohort studies in surgery. These guidelines aim to improve the reproducibility, reliability, and interpretability of surgical research.

3. RESULTS

4. DISCUSSION

The objective of our study was to comprehensively examine the characteristics, outcomes, and treatment responses of patients with chronic pleural effusion. According to the latest studies and sources, the most common causes of chronic pleural effusion in the world are congestive heart failure, then various malignancies, and finally, liver failure. In our patient population, malignancies were identified as the predominant cause of chronic pleural effusion, which is consistent with the referral pattern to our center.

One noteworthy aspect that sets our study apart is the higher prevalence of malignant effusion in younger patients. These findings challenge conventional expectations and underscore the importance of considering malignancy, even in demographics where it may not be the primary consideration. Early detection and management strategies in younger patients are crucial, as highlighted by the need for further investigation into specific malignancies affecting this age group and their variations compared to global patterns.

Regarding the types of malignancies identified, our study found a notable preference for adenocarcinoma among lung malignancies. We recognize the potential interest in exploring the differences between these malignancies in our population compared to other countries. It is essential to acknowledge the limitation of our study concerning the lack of long-term follow-up data. While we presented the immediate response rates, including recurrence rates and follow-up durations, it would offer a more comprehensive understanding of the durability of these treatment outcomes.

Furthermore, investigating any variations in the distribution of other types of malignancies within our study cohort can offer a comprehensive understanding of the spectrum of malignancies contributing to chronic pleural effusion. Future studies with extended follow-up periods are necessary to assess the long-term efficacy of these methods, particularly recurrence rates over time.

By emphasizing the novel findings related to age-specific prevalence and malignancy types, we aim to enhance the relevance of our study in the broader context of global research on pleural effusion.

In the chemical method, after draining the effusion, a sucrose-giving substance (such as tetracycline and bleomycin) is injected into the pleural space using thoracocentesis or thoracoscopy [12, 13].

Recommendations in favor of using ultrasound to guide pleural interventions, not performing pleural interventions in patients without MPE symptoms, and using pleural catheters or chemical pleurodesis in patients with MPE symptoms and suspected expandable lung are very important. Following these recommendations will lead to fewer hospitalizations and better patient outcomes [14, 15]. Researchers want to note that MPE surgical options in the form of thoracic abrasion may be equivalent to chemical pleurodesis in certain scenarios, according to studies [16]. In addition, several other areas of interest have not been fully elucidated [17]. There are not enough studies to compare palliative methods of MPE with antitumor treatment [18].

Considering that MPE is mostly in the late stages of malignant diseases, currently, methods are still more focused on symptom management. It is true that for the most effective treatment, clinicians must be able to detect the underlying disease at an early stage (e.g., breast cancer public health interventions, screening programs, etc.) [19, 20]. Another area of interest with high-quality evidence is the management of trapped lungs in MPE. Researchers believe that using IPC in such an environment is valuable [21, 22]. However, the use of other methods (for example, the use of intrapleural fibrinolytic therapy) may also be useful in certain cases [23]. In addition, there is still no consensus on the MPE drainage volume. Traditionally, in the therapeutic setting, fluid removal was stopped when the total amount of fluid removed reached 1000 to 1500 mL due to the fear of re-expansion of pulmonary edema and pneumothorax. Ault et al. showed that common assumptions about thoracocentesis safety guidelines are usually incorrect [24].

Researchers believe that currently, no maximum volume of fluid can be safely removed during therapeutic thoracocentesis. Decisions regarding the amount of fluid removed should remain within the domain of experienced clinicians [25]. In the present study, out of 95 patients with MPE (malignant pleural effusion), 73 patients (76.8%) were treated with chemical pleurodesis, and 22 patients (23.1%) were treated with mechanical methods. After accessing 61 cases of treated patients, it was found that the mechanical method was 79.9% effective, and the chemical method was 73.8% effective [26, 27]. Future studies with extended follow-up periods are necessary to assess the long-term efficacy of these methods, particularly recurrence rates over time.

The choice between chemical and mechanical pleurodesis was based on the patient’s clinical condition and the physician’s judgment. Chemical pleurodesis was preferred for less invasive treatment, with tetracycline or bleomycin selected based on availability, cost, and physician experience. Mechanical pleurodesis was used when stronger adhesion was needed or when chemical methods had failed. It was sometimes combined with chemical agents to reduce the recurrence of effusions. One of the key findings of our study was the prevalence of MPE among patients with chronic pleural effusion. We found that out of the 144 patients included in the study, 95 patients (66%) had MPE. This highlights the critical need for early identification and treatment strategies, as MPE is frequently associated with late-stage malignancies, significantly impacting patients' quality of life.

Regarding demographic characteristics, we observed that the average age of the patients with chronic pleural effusion was 47.59 years, with a standard deviation of 12.13. This finding aligns with the existing literature, which suggests that pleural effusion is more commonly seen in middle-aged and older individuals (reference). However, we did not find a significant difference when comparing the average age of patients with MPE and other patients. This suggests that age alone may not be a reliable predictor of MPE development in patients with chronic pleural effusion.

The analysis of laboratory findings provided valuable insights into the diagnostic markers associated with MPE. Our results showed a significantly higher number of White Blood Cells (WBC) in patients with MPE compared to those without MPE. This finding aligns with previous studies that have demonstrated the role of elevated WBC count as an indicator of malignancy in pleural effusion (reference). Additionally, we observed a higher Erythrocyte Sedimentation Rate (ESR) and Lactate Dehydrogenase (LDH) level in patients with MPE.

The analysis of pleural fluid characteristics revealed significant differences between patients with MPE and other patients. Patients with MPE had higher levels of protein and LDH in their pleural fluid compared to those without MPE. These findings are consistent with the exudative nature of MPE, characterized by increased pleural fluid protein and LDH levels (reference). Moreover, the presence of lymphocytes in the pleural fluid was significantly higher in patients with MPE.

The prevalence analysis of the type of pleural effusion demonstrated a significant association between the presence of MPE and exudative pleural effusion. A large majority (90.9%) of patients with MPE had an exudative pleural effusion, while only a minority (11.1%) of other patients had the same type. This finding further supports the role of pleural fluid analysis, including protein and LDH levels, in differentiating MPE from other causes of pleural effusion.

The clinical implications of our study findings are noteworthy. Firstly, the high prevalence of MPE among patients with chronic pleural effusion emphasizes the importance of early consideration and evaluation for malignancy in such cases. Prompt diagnosis and appropriate management strategies, such as pleurodesis, can significantly improve patient outcomes and quality of life. Secondly, the diagnostic markers identified in this study, including elevated WBC count, ESR, LDH levels, and lymphocyte presence in pleural fluid, can aid in the identification of MPE and guide clinical decision-making. These markers can contribute to a more targeted and efficient diagnostic approach in patients with pleural effusion. The high prevalence of lymphocyte-predominant exudative pleural effusions among MPE patients further emphasizes the utility of pleural fluid analysis in differentiating malignant from non-malignant causes.

Finally, given the high malignancy rate in this cohort, it is essential to explore region-specific variations in cancer epidemiology and treatment responses. These insights can contribute to the development of tailored strategies that address the unique needs of patients in different demographic and geographic settings. The comparison highlights the clinical importance of distinguishing effusion etiologies and tailors diagnostic and therapeutic approaches accordingly. By emphasizing these differences, our study contributes to the growing body of evidence supporting a targeted diagnostic algorithm for pleural effusions, ensuring timely and accurate management.

CONCLUSION

The results of the present study showed that the most common causes of chronic pleural effusion include malignancies and chronic heart failure, respectively. The most common malignancies included lung malignancies with a preference for adenocarcinoma. By analyzing the amount of protein, LDH, and the number of WBCs and their differentiation in the pleural fluid, it is possible to distinguish malignant pleural effusion from other causes of chronic pleural effusion. Using chemical agents’ tetracycline, bleomycin, and mechanical pleurodesis has greatly improved the symptoms of MPE patients and prevented fluid re-accumulation.

Based on our findings, we recommend comprehensive cytological and biochemical examinations in cases of chronic effusion to improve diagnostic accuracy and guide treatment strategies more effectively. This approach aligns with the evidence presented in our study and could help identify underlying conditions and optimize patient management.

The main limitation of the present study was the lack of access to patients, which was addressed through telephone contact, laboratory data, and patient records.

It is recommended to design and conduct a multicenter cohort study with long-term patient follow-up to evaluate the response to treatment.

REFERENCES