DOI: https://doi.org/10.21203/rs.3.rs-2333941/v1
Community acquired pneumonia (CAP) patients usually combine with parapneumonic pleural effusion (PPE), and complicates the treatment of pneumonia. This study aimed to investigate the clinical characteristics and risk factors of community acquired pneumonia (CAP) patients hospitalized with parapneumonic pleural effusion (PPE) in elderly.
The clinical data of 132 elderly patients with CAP were retrospectively analyzed. 54 patients with PPE (PPE group) and 78 patients without PPE [NPPE (non parapneumonic pleural effusion) group] were included in this study. Clinical data, laboratory examination, treatment and other related indicators were collected. Univariate analysis and multivariate Logistic regression analysis will be used to explore the possible risk factors for PPE.
PPE patients were significantly more likely to be older, comorbid with neurological diseases, occur chest tightness and lasting fever (t = − 2.351, χ༒ = 4.175, χ༒ = 14.103, t = − 2.242, P < 0.05). In contrast to NEEP patients, the total number of lymphocytes, serum albumin and blood sodium levels in PPE group were significantly lower (Z = − 2.634, t = 3.597, t = 2.153, all P < 0.05), blood D-dimer and C-reactive protein (CRP) were significantly higher (Z = − 2.254, t = − 2.380, all P < 0.05), the CURB-65 score was significantly higher (t = -3.543, P = 0.001), the use rate of carbapenems or glycopeptides antibiotics was higher (χ༒ = 5.641, P = 0.018), the length of hospital stay was longer (t=-2.073, P = 0.04), and the in-hospital mortality of PPE patients was significantly higher (χ༒ = 12.551, P < 0.001). Multivariate Logistic regression analysis showed that chest tightness (OR = 3.964, 95%CI: 1.254 ~ 12.537, P = 0.019), long duration of fever (OR = 1.108, 95%CI: 1.009 ~ 1.217, P = 0.032), low serum albumin (OR = 0.876, 95%CI: 0.790 ~ 0.971, P = 0.012) and low blood sodium (OR = 0.896, 95%CI: 0.828 ~ 0.969, P = 0.006) were significant risk factors for elderly CAP patients combine with PPE.
A risk factor analysis was performed, elderly patients with CAP have a higher incidence of PPE, higher mortality and longer hospital stay. Chest tightness, long duration of fever, low serum albumin and low blood sodium are risk factors for PPE.
Parapneumonic pleural effusions occur as a result of bacterial pneumonia, lung abscess, or bronchiectasis, and complicated with pneumonia commonly[1]. It has been reported in the literature that 15%-44% of hospitalized patients with community acquired pneumonia (CAP) have PPE, about 5% of pneumonia patients have complex parapneumoniae pleural effusion and empyema, and about 33% of PPE and chest drainage that do not respond to antibiotic treatment require surgery[2-4]. Concomitant PPE complicates the treatment of pneumonia, and despite advances in antibiotic treatment, PPE morbidity and mortality have increased over the past 20 years[5]. As the case fatality rate increases, PPE patients require longer hospital stays and more interventions, so the identification and timely management of these patients is critical[6]. In recent years, with the continuous development of the aging society, the incidence of CAP in the elderly is increasing, and the occurrence of PPE is more common[7]. However, there are few PPE related research data for elderly people with CAP. In this study, clinical data of 132 elderly patients with CAP were retrospectively analyzed to explore the risk factors for PPE.
A retrospective cohort study was conducted at the Department of Respiratory and Critical Care Medicine of the Third Affiliated Hospital of Anhui Medical University, clinical data in 132 elderly patients diagnosed with CAP were collected between January 2019 to December 2019. Subjects were included in the study if they fulfilled the fellow criteria: Age ≥ 65 years old, according to the diagnostic criteria of Chinese Adult Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia published by the Respiratory Branch of the Chinese Medical Association in 2016[8]. Subjects with any of the following were excluded criteria[9–10]: comorbidities (malignant tumors, active tuberculosis, and hematological diseases); severe immunosuppressive (using longtime high dose of immunosuppressive agents, chemotherapy or solid organ transplantation, post-splenectomy, HIV infection); severe cardiac, renal or liver dysfunction; Hospital acquired pneumonia; research-related data missing (Fig. 1).
Depending to imaging data (chest X-ray, chest CT or chest B-ultrasound), patients were divided into PPE group 54 cases, including 34 males and 20 females, the age of the patients ranged 69 ~ 96 yrs (average 81.7 ± 7.1 yrs). Among the 54 PPE patients, there were 42 cases of unilateral pleural effusion and 12 cases of bilateral pleural effusion. Among them, 41 patients underwent thoracentesis and drainage, all of which were exudates with a total drainage volume of about 400 to 1500 ml, 13 patients did not undergo puncture due to low pleural effusion volume or high puncture risk. There were 78 cases in the NPPE group, including 41 males and 37 females, the age of the patients ranged 65 ~ 99 yrs (average 78.4 ± 8.5 yrs). The Clinical Research Ethics Coimmittee of the the Third Affiliated Hospital of Anhui Medical University approved this study. [LUN Research Grant No. 2020 (20)].
Data collection: we retrospectively extracted the following patient data by reviewing medical records, general conditions, underlying diseases, symptoms, signs, laboratory examination, imaging data, etiology examination, antibiotic use, length of stay and prognosis of patients. The disease course prior to hospital admission refers to the time from the discovery of clinical symptoms to admission. Quit smoking refers to having quit smoking for at least 6 months.
Record the CURB-65 score.The CURB-65 score consists of 5 points: confusion, blood urea nitrogen > 7 mmol/L, respiratory rate > 30 breaths/min, systolic blood pressure < 90 mmHg and/or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs [11]. One point for each item above.
All data were analyzed using Statistical Package for Social Sciences (SPSS) version 25. Quantitative data, which were normally distributed, were described by mean and standard deviation(± s), comparison between groups were analyzed with the two independent sample t-test; Mann–Whitney U-test was used for calculating differences between data of two groups which were not normally distributed and expressed as median IQR; For qualitative data, the pearson chi-square test were used to assess differences and expressed by case or percentage; Multivariate logistic regression model of binary variables will be used to analyze PPE risk factors. Statistical significance was assumed at P < 0 .05.
CAP patients hospitalized with PPE were more likely to be older and comorbid with neurological diseases (such as stroke, Parkinson's disease, senile dementia, etc). The sex ratio, smoking status, previous hypertension, coronary heart disease, chronic cardiac insufficiency, chronic obstructive pulmonary disease, diabetes and renal insufficiency were similar in the two groups (all P > 0.05, Table 1).
The incidence of chest tightness and duration of fever in PPE group were significantly higher than those in NPPE group (P < 0.05). The CURB-65 score in PPE group was significantly higher than that in NPPE group (t=-3.543, P = 0.001). There were no significant differences in the proportion of fever, cough, chest pain, altered consciousness, maximum body temperature during the course of the disease and the number of days of illness before admission between the two groups (all P > 0.05). The results are shown in Table 2.
The total number of lymphocytes, serum albumin and blood sodium levels in PPE group were significantly lower than those in NPPE group (P < 0.05). Blood D-dimer and C-reactive protein (CRP) in PPE group were significantly higher than those in NPPE group (P < 0.05). There was no significant difference in other indexes between the two groups (all P > 0.05). The results are shown in Table 3.
In these recruited patients, 113 underwent etiological examination(sputum smear and culture, alveolar perfusion fluid, pleural effusion, blood culture and serum detection of pathogen antibodies), the etiological submission rates 87.1% (47/54) of the PPE group and 84.6% (66/78) of the NPPE group. In NEEP group, there were 22 positive results, among these, in sputum smear, 7 Gram-negative bacilli (the bacteria species could not be identified); in sputum culture, 7 Candida albicans, 2 Pseudomonas aeruginosa, 1 Escherichia coli, and 1 Klebsiella ornitholyticus; in blood culture,1 Escherichia coli, 3 Mycoplasma pneumoniae. While in EEP group, 23 positive results were present (42.6%, including 2 mixed infection with two pathogens), among these, in sputum smear, 5 Gram-negative bacilli (the bacteria species could not be identified); in sputum culture, 4 Candida albicans, 1 Candida parapsilosis, 2 Staphylococcus aureus,2 Serratia marcescens, 2 Acinetobacter baumannii,1 Pseudomonas aeruginosa,1 Klebsiella pneumoniae, 1 Escherichia coli, 1 Haemophilus influenzae; in blood culture, 1 Escherichia coli, 1 Staphylococcus aureus, and 1 Staphylococcus hemolytic; in pleural effusion culture, 1 Streptococcus agalactiae.
All patients with CAP received intravenous antibiotics therapy, including β-lactam, β-lacamase inhibitors, quinolones, macrolides, carbapenems or glycopeptides, and triazoles. NPPE patients were treated with single drug mostly, second-generation cephalosporins, third-generation cephalosporins or β-lactamase inhibitors were mainly used; the utilization rate of carbapenems or glycopeptides was 10.3% (8/78); the proportion of combined drug was 19.2% (15/78). PPE patients were treated with β-lactamase inhibitors mostly, the utilization rate of carbapenems or glycopeptides was 25.9% (14/54), and the proportion of combined drugs was 22.2% (12/54). Compared with the NPPE patients, the use rate of carbapenems or glycopeptides was higher (χ༒ = 5.641, P = 0.018), the length of hospital stay was longer (t=-2.073, P = 0.04), and the in-hospital mortality of PPE patients was significantly higher (χ༒ = 12.551, P < 0.001) in the PPE patients. The results are shown in Table 4.
In the above univariate analysis, there were some significant factors as independent variables, such as age, neurological disease (yes/no), symptoms of chest tightness (yes/no), duration of fever (yes/no), total lymphocyte count, serum albumin, serum sodium, D-dimer, CRP, CURB-65 score, and pleural effusion (yes/no) as dependent variables (assigned: Yes = 1, no = 0), multivariate Logistic regression analysis was performed. Of course, chest tightness, long duration of fever, low serum albumin and low blood sodium were significant risk factors for elderly CAP patients combine with PPE (all P < 0.05). The results are shown in Table 5.
Community-acquired pneumonia (CAP) is an increasing problem in the elderly, with literature reporting that about 45–50% of all CAP hospitalizations occur in patients 65 yrs of age or older[12]. Poor clinical outcomes and increased mortality can be associated with the development of parapneumonic effusions[13]. In this study, a retrospective analysis of the clinical data of 132 elderly patients with CAP in our hospital showed that the proportion of elderly patients with CAP combined with PPE was 40.9%, and the in-hospital mortality of pneumonia patients with PPE was significantly higher than that of patients with pneumonia alone. Therefore, the study of clinical characteristics of elderly patients with CAP combined with PPE is conducive to reinforce the importance of early recognition, diagnosis and treatment.
In addition to the inflammatory and virulent features of the lungs and pleura due to direct bacterial invasion that lead to PPE, the physical conditions and underlying diseases of patients also contribute to the pathophysiological development of PPE. In this study, the middle-edged and older adults with CAP mostly have more basic diseases, and 87.1% of the patients combine with at least one disease. The existence of underlying diseases is an important risk factor for elderly pneumonia, which will lead to the reduction of the body's resistance to infection and increase the development of pneumonia and the risk of death[14]. In the previous studies, there were some common complications of PPE, such as diabetes mellitus, malignancy, chronic excessive alcohol consumption, chronic lung disease, immunosuppressive states, aspiration,etc[15–16]. But in this study, the proportion of PPE patients with the nervous system diseases is higher, which is related to the increased risk of aspiration pneumonia in elderly patients with nervous system diseases, aspiration is widely recognized as an important risk factor for pneumonia[17], for the first time after aspiration pneumonia, 1-month mortality was 23.9% in patients with Parkinson's disease, about two-thirds of the patients died within a year after the aspiration pneumonia[18–19]. The PPE group in-hospital mortality is higher in this study, considering these patients had significantly older ages, long-term bedridden, cognitive impairment, or swallowing dysfunction, onset is given priority to with aspiration pneumonia or more lung infiltrates, these tend to make a delayed diagnosis and treatment after onset, or their families have poor willingness in invasive operation such as endotracheal intubation in the treatment of intention. therefore, PPE patients had higher in-hospital mortality rate than NPPE. In addition, the PPE group did not have a high proportion of diabetes, considering the sample size was relatively small, thus we still had a potential selection bias.
In terms of etiology, in this study, 42.6% of patients in the PPE group were detected with pathogenic bacteria in order as follows: G–Bacillus, Candida and Staphylococcus. The commonest infection of G–Bacillus were Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, 1 case of pleural effusion was cultured as Streptococcus agalactiae. A meta-analysis of Hassan, etc[20] showed that the most common aerobic isolates in pleural effusion culture were Staphylococcus aureus (20.7%), Streptococcus aerophylus group (18.7%), Pseudomonas (17.6%), Enterobacteriaceae (11.9%), Streptococcus pneumoniae (10.8%), Klebsiella (10.7%), Acinetobacter (5%) and coagulase negative Staphylococcus (4.5%). In this study, the distribution of pathogenic bacteria was different from that in the literature. On the one hand, the pathogenic specimens were different, and on the other hand, because of the empirical antibiotic therapy before the specimens were submitted for examination, the positive rate of pathogenic bacteria was not high. With the appearance of whole genome next generation sequencing, we may overcome some of the shortcomings of standard microscopy and culture techniques. In this way, more or less common pathogens will be identified, which will be more helpful for clinical decision making.
In order to treat PPE, the most basic is prompt clean the infection of intrathoracic and using antibiotics, which should be guided by specific pathogen sensitivity[21]. In culture-negative PPE, empirical use of antibiotics should be based on local pathogenic distribution, drug resistance, and antibiotic management policies. The British Thoracic Society[22] (BTS) and American Association for Thoracic Surgery[23] advice that broad-spectrum antibiotics should be used before the pathogens are confirmed, which covers Gram-positive, Gram-negative and anaerobic, such as β-lactamase inhibitors, third-generation cephalosporins and carbapenems, etc. Consistent with recommendations, compared with the NPPE group, the use of antibiotics in the PPE group in this study was mainly β-lactam inhibitors, and the utilization rate of carbapenems or glycopeptides was 10.3% (14/54), which was significantly higher than that in the NPPE group, which was mainly related to the pathophysiological characteristics of the PPE group and the severity of patients' disease.
Clinically, patients often present with pleuritic chest pain due to inflammation of the pleura, but it is uncommon in the PPE group (11.11%), and 6.41% of patients still have chest pain without effusion, so we cannot diagnose pleurisy only by chest pain. Dyspnea is the most common manifestation of pleural effusion, and the severity of dyspnea has little obvious correlation with the amount of effusion, and it may be associated with abnormalities in gas exchange, respiratory mechanics, respiratory muscle function and hemodynamics, which are caused by pleural effusion[24–25]. Although 20.51% of the NPPE patients had chest tightness, the proportion of chest tightness and dyspnea in the PPE group was higher (51.85%), and chest tightness was an independent risk factor for PPE. Therefore, it should be vigilant that whwther the elderly CAP patients with chest tightness complicated with pleural effusion or not. Our study demonstrated that PPE patients were easier to present long-term fever, suggesting that fever, as a clinical marker of inflammation, lasted longer in patients with pleural effusion. Whereas the persistence of fever in patients with pneumonia can complicate the conditions, and suggests that inflammation persists[26].
Because of the persistence of pleural inflammation, inflammatory markers are significantly elevated in PPE and empyema patients[27]. The results of this study showed that there were no significant differences in peripheral white blood cells count, neutrophil count and PCT between the PPE and the NPPE patients, while the CRP level in the PPE group was significantly higher than that in the NPPE group. As a classic inflammatory marker, CRP is widely used in the diagnosis of infectious diseases[28]. In a previous study, pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions[29]. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology. The study of Petrusevska - Marinkovic, etc[16] suggests that the CRP in the complex PPE patients was significantly higher than that in the simple PPE patients [(231.79 ± 112.2) mg/L vs. (163.8 ± 147.9) mg/L, P < 0.01], and both were significantly higher than that in the CAP patients without effusion [(139.48 ± 105.7) mg/L, P < 0.01]. Patients whose CRP does not decline with treatment during the course of the disease are at significantly higher risk for complex PPE or empyema. D-dimer is an objective biomarker for reflecting coagulation and fibrinolysis. The reasons for the formation of PPE include the interaction between inflammation and coagulation as well as the occurrence of intrapleural fibrosis. The microcirculation thrombosis and extracellular fibrin remodeling usually with elevated D-dimer levels[30]. In this study, PPE patients have significant elevated D-dimer levels, indicating the disorder of coagulation and fibrinolysis. Multivariate logistic regression analysis revealed that serum albumin (OR = 0.876, 95%CI: 0.790–0.971, P = 0.012) and serum sodium (OR = 0.896, 95%CI: 0.828–0.969, P = 0.006) is also an independent risk factor for PPE in elderly patients with CAP, which is consistent with previous studies[31].
There were some limitations in this study. Firstly, as a retrospective observational study, the number of cases was small and some data were missing. Second, for some patients with pleural effusion, the B-ultrasound showed less effusion and could not be extracted safely, so the relevant laboratory indicators of pleural effusion were not analyzed. Third, due to the limited sample size, further stratified comparison could not be carried out, and the accuracy and application value of the results still need to be confirmed by further in-depth research.
As one of the most common complications of pneumonia, PPE is an increasing problem in the elderly that is associated with elevated morbidity and mortality. For elderly patients with CAP, early diagnosis and treatment are very important. According to the actual situation of elderly patients, antibiotics should be correctly selected, the underlying diseases should be actively treated, hypoproteinemia and electrolyte disorder should be corrected timely, and adequate drainage should be placed timely, which can shorten the length of hospital stay, reduce the occurrence of complications and reduce the mortality.
CAP: Community acquired pneumonia
PPE: Parapneumonic pleural effusion
NPPE: Non parapneumonic pleural effusion
CRP: C-reactive protein
PCT: Procalcitonine
IOR:Interquartile range
Year: Yr
CI: Confidence interval
Ethics approval and consent to participate
All experiments were performed in accordance with relevant guidelines and regulations. This study was approved by the Ethics Committee of the Third Affiliated Hospital of Anhui Medical University, and all participants and/or their legal guardian(s) signed the informed consent form.
Consent for publication
Not applicable.
Availability of data and materials
All data generated or analyzed during this study are included in this published article [and its supplementary information fles].
Declaration of competing interest
The authors have declared that no competing interests exist.
Authors’ contributions
Mingmei Zhong and Ruiqin Ni contributed equally to this work, and should be regarded as co-first authors, they carried out the laboratory analyses, acquired of funding, drafted the manuscript, collected data, conceived of the study, participated in its design, coordination and helped to draft the manuscript. Huizhen zhang and Yangyang Sun performed the statistical analysis and helped to draft the manuscript. All of the authors read and approved the final version of the manuscript.
Acknowledgement
This work was supported by grants from Hefei Municipal Health Commission Applied Medical Research Project (Hwk2020zd002).
Funding
This work was supported by Hefei Municipal Health Commission Applied Medical Research Project (Hwk2020zd002)
Author information
Mingmei Zhong1, The Third Affiliated Hospital of Anhui Medical University
Ruiqin Ni1, Bengbu Medical College
Huizhen Zhang2, The Third Affiliated Hospital of Anhui Medical University
Yangyang Sun3, Bengbu Medical College