Elevated eosinophils predict acute exacerbations in patients with chronic obstructive pulmonary disease.

doi:10.21203/rs.3.rs-5095745/v1

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Elevated eosinophils predict acute exacerbations in patients with chronic obstructive pulmonary disease.

https://doi.org/10.21203/rs.3.rs-5095745/v1

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Background: This research aims to determine the prevalence of blood eosinophilia in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its association with the severity of the exacerbation.

Methods and materials: The study included 105 patients with acute exacerbation of COPD admitted to Aleppo University Hospital during the period from 1/3/2023 to 1/3/2024, 29 patients had eosinophilia at admission and 76 patients did not have eosinophilia at admission. The prevalence of comorbidities was compared between these two groups and the inflammatory activity accompanying the exacerbation in each of them was studied through clinical and laboratory indicators which are associated with the severity of the exacerbation, using appropriate statistical tests such as the Independent Sample T Test and Chi square, and through the SPSS-26 program.

Results: The prevalence of blood eosinophilia in patients with acute exacerbation of COPD at admission was 27.6%. Patients with no eosinophilia were characterized by higher mean values of leukocyte count, neutrophils, ESR, and CRP (higher mean values of which correlate with severity of the exacerbation) and lower mean value of platelets (lower mean values of which correlate with severity of the exacerbation), as well as the incidence of acute respiratory failure, the need for non-invasive and invasive mechanical ventilation, the mean of length of stay in hospital and mortality were greater in this group compared to who do not have eosinophilia.

Conclusions: Blood eosinophilia is quite common (27.6%) in patients with acute exacerbation of COPD, and patients who have eosinophilia at admission have less exacerbation severity clinically and laboratory compared to patients who do not have eosinophilia.

Pulmonology

The patients with acute exacerbation of COPD

eosinophilia

exacerbation severity

mortality

Chronic obstructive pulmonary disease (COPD) is a condition that significantly affects global public health and is considered one of the leading causes of premature death. This disease presents a major challenge, especially with the continuous aging of the population and ongoing exposure to risk factors such as smoking and air pollution. As the number of cases increases, there is a growing need to enhance prevention efforts through awareness campaigns and reducing exposure to these risk factors. Additionally, improving diagnostic and treatment systems helps reduce the burden associated with this disease. [1]

The study, a retrospective prospective study, was conducted at Damascus Hospital, with data collected over 13 years, from the beginning of March 2013 to the beginning of March 2024. The study included 125 patients admitted to the pulmonary department at Damascus Hospital, who had complete information during this period and presented with an acute exacerbation of chronic obstructive pulmonary disease (COPD). These patients had been previously diagnosed with COPD through pulmonary function testing conducted outside of exacerbation episodes.

The study comprehensively included clinical history (medical and drug history and risk factors), clinical examination, necessary laboratory tests (including blood eosinophil count, with the normal range being 0–500 cells/µL based on the laboratory standard), chest X-rays, and computed tomography (CT) scans of the chest when needed to rule out differential diagnoses. Complications during hospitalization were also investigated. The following inclusion and exclusion criteria were applied:

Inclusion Criteria:

Patients with acute COPD exacerbations admitted to Damascus Hospital over the 13-year study period.

Exclusion Criteria:

Patients with blood disorders or malignancies.

Patients taking medications that affect eosinophil count (such as corticosteroids).

Patients with allergic diseases like allergic asthma.

Patients with rheumatic diseases, connective tissue diseases, or vasculitis with elevated eosinophils (e.g., Churg-Strauss syndrome).

Patients with parasitic or fungal infections.

Incomplete data from medical records.

After applying the above criteria, 105 patients were included in the study. The prevalence of eosinophilia was determined, and the patients were divided into two groups based on the presence of eosinophilia as follows:

Patients with an eosinophil count at admission < 300 cells/µL.

Patients with an eosinophil count at admission ≥ 300 cells/µL (this threshold was used based on several previous studies, as well as recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), to assess the potential response to inhaled corticosteroid treatment in stable patients).

Several comparisons were made between the two groups to study the relationship between eosinophilia and the severity of COPD exacerbations.

Statistical Analysis:

Statistical tests were performed using SPSS-26 software. Numerical variables were compared using Pearson, Independent Sample T-Test, and Spearman tests. Means and standard deviations were calculated for these variables. Categorical variables were compared using Chi-square and Fisher's exact tests, with the p-value calculated. Statistical significance was considered when the p-value was less than 0.05.

First: General Distribution Studies:

Age Distribution of Study Patients:

The ages of the study patients ranged from 46 to 87 years, with a median age of 63.18 years and a standard deviation of 16.74 years.

When dividing the patients by different age groups, it was found that five patients were between 40–49 years old, representing 4.8% of the total patients. 21patients were between 50–59 years old, making up 20%.

39 patients were aged between 60–69 years, accounting for 37.1%. 34 patients were between 70–79 years old, representing 32.4%. Six patients were over 80 years old, constituting 5.7%.

Gender Distribution of Study Patients:

The total number of males in the study was 78, representing 74.3%, while the number of females was 27, making up 25.7%.

Prevalence of Comorbidities and Smoking Among Study Patients:

Hypertension was the most common comorbidity among the study patients, present in 37 patients, accounting for 35.2% of the total. Ischemic heart disease was found in 33 patients, representing 31.4%. Diabetes mellitus affected 26 patients, making up 24.8% of the patients. Chronic kidney disease was present in 9 patients, or 8.6%. Additionally, 91 patients were smokers, representing 86.6% of the study population.

The mean body mass index (BMI) of the study patients was 23.7 kg/m², with a standard deviation of 4.5 kg/m².

Clinical Manifestations and Examination Findings in Study Patients:

As is well known, the three primary symptoms that patients with an acute COPD exacerbation experience are worsening shortness of breath, increased frequency of coughing, and an increase in sputum production or a change in its characteristics (purulence). In our study, shortness of breath was the most common symptom, affecting 101 patients (96.1%). This was followed by an increased frequency of coughing and increased or purulent sputum, observed in 89 patients (84.8%) and 77 patients (73.3%), respectively.

Systolic Blood Pressure: The mean systolic blood pressure was 129.38 mmHg with a standard deviation of 24.26 mmHg. The minimum was 80 mmHg, and the maximum was 175 mmHg.

Pulse Rate: The mean pulse rate was 94.25 beats per minute, with a standard deviation of 17.49 beats per minute. The minimum was 57 beats per minute, and the maximum was 146 beats per minute.

Respiratory Rate: The mean respiratory rate was 29.35 breaths per minute, with a standard deviation of 6 breaths per minute. The minimum was 24 breaths per minute, and the maximum was 38 breaths per minute.

Temperature: The mean body temperature was 38.6°C with a standard deviation of 0.51°C. The minimum was 37.3°C, and the maximum was 40.2°C.

SpO2: The mean oxygen saturation (SpO2) was 90.28% with a standard deviation of 8.16%. The minimum was 77%, and the maximum was 98%.

Comparison between the two study groups:

As previously mentioned, the patients were divided into two groups: Patients with COPD and Elevated Eosinophils: This group included 29 patients, accounting for 27.6% of the total. Patients with COPD without Elevated Eosinophils: This group consisted of 76 patients, representing 72.4% of the total.

Comparison of Mean Age Between the Two Groups :

Patients with Elevated Eosinophils: Their ages ranged from 48 to 87 years, with a mean age of 65.3 years and a standard deviation of 12.6 years. Patients without Elevated Eosinophils: Their ages ranged from 46 to 83 years, with a mean age of 62.9 years and a standard deviation of 11.7 years.An Independent Sample T-Test revealed no statistically significant difference between the two groups (P-value = 0.281).

Comparison of Gender Distribution Between the Two Study Groups:

Patients with Elevated Eosinophils: This group included 22 males, representing 75.9%, and 7 females, representing 24.1%. Patients without Elevated Eosinophils: This group included 56 males, accounting for 73.7%, and 20 females, making up 26.3%.There was no statistically significant difference in gender distribution between the two groups.

Comparison of the prevalence of comorbidities and smoking between the two study groups:

When examining the prevalence of comorbidities and smoking in each study group separately, it was found that hypertension, diabetes, chronic kidney failure, and smoking were more prevalent in patients with elevated blood eosinophil levels, although there was no statistically significant difference between the two groups. On the other hand, ischemic heart disease was more prevalent in patients without elevated blood eosinophils, but again, there was no statistically significant difference.

In comparison of the mean Body Mass Index (BMI) between the two study groups, it was found that the average BMI was similar between the two groups.

Comparison of the incidence of COPD exacerbations over the past year between the two study groups:

The presence of previous exacerbations was investigated in the study patients during the year prior to their hospital admission, specifically looking for the occurrence of two or more COPD exacerbations during this period. It was found that the incidence of exacerbations was higher in patients with elevated blood eosinophil levels compared to those without elevated blood eosinophils (75.9% vs. 67.1%), with a statistically significant difference.

Comparison of the prevalence of key clinical manifestations of COPD exacerbations between the two study groups:

In our study, we found that the prevalence of increased shortness of breath, increased cough frequency, and increased sputum production were similar between the two study groups.

Comparison of arterial blood oxygen saturation (SPO2) at admission between the two study groups:

Arterial blood oxygen saturation (SPO2) is one of the most important vital signs associated with the severity of acute COPD exacerbations. The study revealed that the mean SPO2 values at admission were lower in patients without elevated blood eosinophil levels compared to those with elevated blood eosinophils (86.4% vs. 92.6%), with a statistically significant difference between the two groups.

Comparison of laboratory test results between the two study groups:

Several inflammatory laboratory markers are associated with the severity of acute COPD exacerbations, such as elevated levels of white blood cells, neutrophils, CRP, and ESR, as well as decreased platelet counts. Therefore, the mean values of these laboratory tests were compared between the two study groups. It was found that the mean values of white blood cell count, neutrophils, CRP, and ESR were higher in patients with elevated blood eosinophils, with statistically significant differences in white blood cells, neutrophils, and CRP. Hemoglobin levels were similar between the two groups, while platelet counts were lower in patients without elevated blood eosinophils, but this difference was not statistically significant.

Comparison of the incidence of respiratory failure during hospitalization between the two study groups:

Since respiratory failure is the most significant complication during hospitalization in patients with acute COPD exacerbations, the incidence of respiratory failure was compared between the two study groups. It was found that the incidence of acute respiratory failure during hospitalization was higher in patients without elevated blood eosinophils compared to those with elevated blood eosinophils (27.6% vs. 17.2%), with a statistically significant difference.

Comparison between the two study groups regarding the need for admission to the Intensive Care Unit (ICU) during hospitalization:

Three patients with elevated blood eosinophils were admitted to the ICU, representing 10.3%, while 16 patients without elevated blood eosinophils were admitted to the ICU, representing 21.05%. This difference between the two groups was statistically significant.

Comparison between the two study groups regarding the need for mechanical ventilation during hospitalization:

Mechanical ventilation, both invasive and non-invasive, is one of the most critical interventions for managing acute respiratory failure during hospitalization in patients with acute COPD exacerbations. The need for invasive and non-invasive mechanical ventilation was compared between the two study groups. The proportion of patients who required invasive and non-invasive mechanical ventilation during hospitalization was higher in the group without elevated blood eosinophils compared to the group with elevated blood eosinophils (22.4% vs. 13.7% for invasive ventilation and 10.5% vs. 6.9% for non-invasive ventilation). A statistically significant difference was found only for non-invasive ventilation.

Comparison of the Average Number of Hospitalization Days Between the Two Study Groups:

The average number of hospitalization days was lower among patients without elevated blood eosinophil levels compared to those with elevated blood eosinophil levels, with a statistically significant difference.

Comparison of mortality rates between the two study groups:

Death is one of the most significant complications during the clinical course of acute COPD exacerbations. In our study, the overall mortality rate was 8.6% (9 patients). When comparing the mortality rates between the two study groups, it was found that the mortality rate was higher in patients without elevated blood eosinophils compared to those with elevated blood eosinophils (9.2% vs. 6.9%), but the difference between the groups was not statistically significant.

Chronic Obstructive Pulmonary Disease (COPD) is one of the most common and significant chronic pulmonary diseases. It is also a leading cause of hospital admission, particularly during acute exacerbations of the pre-existing chronic condition. Many indicators, especially laboratory markers, associated with the severity of acute COPD exacerbations have been studied. One of the newly studied markers is blood eosinophil count, which is the focus of this research.

The number of patients in our current study was 105, with an average age of 63.18 years. The study included 78 males (74.3%) and 27 females (25.7%).

The most common comorbidity in our study was hypertension, present in 37 patients (35.2% of the total patients), followed by ischemic heart disease, which was present in 33 patients (31.4%), and diabetes, found in 26 patients (24.8%). The number of smokers was 91 (86.6%). The average body mass index (BMI) among study patients was 23.7 kg/m² with a standard deviation of 4.5 kg/m².

The most common symptom among the study patients was worsening dyspnea, affecting 96.1% of patients, along with increased frequency of coughing and sputum production in 84.8% and 73.3% of patients, respectively. The average SpO2 in the sample was 90.28%, with a standard deviation of 8.16%.

The prevalence of elevated blood eosinophils among the study patients was 27.6%. Based on this, the patients were divided into two groups: the first group included patients with elevated blood eosinophils, and the second group included patients without elevated blood eosinophils. When comparing the average ages between the two study groups, no statistically significant difference in average age was found (65.3 years vs. 62.9 years). Similarly, there was no significant difference in gender distribution between the two groups.

Regarding the prevalence of comorbidities, there were no significant differences in their prevalence, nor in the average BMI between the two groups. Thus, the influence of age, gender, and comorbidities on the severity of the exacerbation between the two groups was ruled out.

We found that the frequency of COPD exacerbations during the year prior to hospitalization was higher in patients with elevated blood eosinophils compared to those without elevated eosinophils (75.9% vs. 67.1%), with a statistically significant difference.

In our study, we found that the average SpO2 upon admission in patients without elevated eosinophils was lower than in those with elevated eosinophils (86.4% vs. 92.6%), with a statistically significant difference between the two groups. This indicates that the severity of exacerbation at the time of admission was greater in patients without elevated eosinophils, as arterial oxygen saturation (SpO2) is one of the most important vital signs associated with the severity of acute COPD exacerbations.

When comparing laboratory tests related to inflammatory activity between the two study groups, we found that patients without elevated eosinophils had higher median values for white blood cell count, neutrophils, CRP, and ESR, and lower median values for platelet count, with statistically significant differences in white blood cells, neutrophils, and CRP. This confirms the increased inflammatory activity associated with COPD exacerbations in patients without elevated eosinophils compared to those with elevated eosinophils.

Clinically, our study showed that the incidence of acute respiratory failure, ICU admission, and the need for non-invasive and invasive mechanical ventilation were higher in the group without elevated eosinophils than in the group with elevated eosinophils, with statistically significant differences in most of these variables. Additionally, the average number of hospitalization days and mortality rate were higher in patients without elevated eosinophils compared to those with elevated eosinophils, with a statistically significant difference only for the average number of hospitalization days.

Thus, we conclude that the clinical course of the disease in our study was less severe in patients with elevated eosinophils compared to those without elevated eosinophils. This is likely because patients with a blood eosinophil count > 300 cells/µL respond better to systemic corticosteroids, which are used to treat acute COPD exacerbations. This response is explained by the anti-inflammatory effects of corticosteroids on the various inflammatory mediators produced by eosinophils, as previously mentioned.

The results of the current study indicate that elevated blood eosinophils are relatively common among patients with acute COPD exacerbations. Patients with elevated eosinophils at the time of admission experience less severe exacerbations both clinically and in laboratory findings. However, the rate of acute exacerbations in the previous year is higher in these patients compared to those without elevated eosinophils.

Ethics approval and consent to participate

The study protocol was approved by the Research Ethics Committee of Syrian Private University and the relevant ethics committees of Syrian Private University, and all procedures performed in the studies involving the participant and subjects 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.

Consent for publication

Not applicable.

Availability of data and materials:

All data produced in the present work are contained in the manuscript

Convict of interest:

The authors declare that they have no convict of interest.

Funding:

This research received no speciﬁc grant from SPU or any other funding agency in the public, commercial or non-profit.

Acknowledgments

We are thankful to the management of Syrian Private University and Damascus Hospital for their support in the eld of medical training and research.

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442.

The authors declare no competing interests.

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Version 1

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Elevated eosinophils predict acute exacerbations in patients with chronic obstructive pulmonary disease.

Status:

Version 1

Abstract

Introduction

Methods and materials

Inclusion Criteria:

Exclusion Criteria:

Statistical Analysis:

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1