Role of cholesterol, lipoproteins, and neutrophilic-lymphocytic ratio in patients with pneumonia

Lipids play numerous functions in lung biology and pathophysiology of infection, in addition to their role in lipid transport, lipoproteins share in innate immunity that is the most important way for the host to defend against microbes. The NLR (neutrophil-lymphocytic ratio) is a good indicator of systemic inflammation and infection. To evaluate the role of cholesterol, lipoproteins, and neutrophilic-lymphocytic ratio in the assessment of patients with pneumonia. This prospective case–control study included 52 subjects; they were categorized into 2 groups. Group A included 42 patients with pneumonia admitted to the Chest Department,Menoufia University, and group B included 10 healthy people during the period from May 2019 to December 2019. History taking, clinical examination, laboratory investigation in the form of CBC and lipid profile, and radiological investigation in the form of CXR and CT chest if needed were done to all subjects of the study. The mean cholesterol level in group A was 149.76 ± 42.79 which was statistically significantly lower as compared with group B (165.90 ± 45.50) (p = 0.039). The mean HDL level in group A was 43.16 ± 6.32 which was statistically significantly lower as compared with group B (50.51 ± 9.60) (p = 0.026). No statistically significant difference was found in the triglyceride level, LDL level and VLDL between the subjects in the two studied groups (p = 0.479, 0.792, and 0.606), respectively, but all levels were still within normal levels. Mean NLR in group A was 7.04 ± 7.98 which was statistically significantly higher as compared with group B (3.04 ± 1.6) (p = 0.004). Roc curve of neutrophil–lymphocyte ratio shows that the cutoff point is 1.94 and the N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity. Serum cholesterol and high-density lipoprotein levels significantly decreased in patients with pneumonia when compared to the control group but were still within normal range. Lipid profile is affected by different variables like smoking index, body mass index, and sex. The neutrophil–lymphocyte at cutoff point is 1.94, and N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity. TCTR, TCTR20220524001. Registered on 24 May 2022, retrospectively registered.


Introduction
Pneumonia is defined as an inflammatory disease of the lungs that affects the alveoli. Symptoms include a combination of productive or dry cough, chest pain, fever, and dyspnea. The severity of the illness varies. Pneumonia is

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The Egyptian Journal of Bronchology most commonly caused by viruses and bacteria, but it can also be caused by other microbes [1].
Lipoproteins are classified as chylomicrons, verylow-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) according to their relative density. Lipoproteins play a major function in innate immunity, which is the most critical line of protection against pathogens, in addition to transporting lipids [2].
In addition, anti-inflammatory effects of lipoproteins, especially HDL, have been demonstrated both in vitro and in vivo studies. Circulating lipoproteins detoxify lipopolysaccharide and toxins of gram-negative and lipoteichoic acid of gram-positive bacteria [3,4].
In patients with infection there was a decrease in the serum levels of total cholesterol, LDL, and HDL, These changes were independent of the underlying disease or microorganisms [5].
The neutrophil-lymphocyte ratio (NLR) is a low-cost, basic diagnostic of systemic inflammation that can predict prognosis in a variety of diseases. It is determined by dividing the absolute neutrophil count by the absolute lymphocyte count, which is obtained from CBC [6].
The aim of the work was to evaluate the role of cholesterol, lipoproteins, & neutrophilic-lymphocytic ratio in the assessment of patients with pneumonia.

Study design
A prospective case-control study was done on a group of 42 cases with pneumonia admitted to the Chest Department of Menoufia University and El Mahalla Chest hospital (group A). In addition, a group of 10 healthy people was included as a free group (Group B) during the duration from May 2019 to December 2019. A written informed consent was obtained from every participant or his representatives prior to inclusion in the study after a detailed explanation of the work, and approval from Menoufia Ethical Committee was obtained.
Inclusion criteria include the following: presence of a major infection criterion (productive cough, body temperature more than 37.8 °C) or 2 minor infection criteria (pleurisy, dyspnea, pulmonary consolidation by clinical examination), leukocytosis > 10 3 /mm3, and pulmonary consolidation verified by chest radiography [7].
Exclusion criteria include the following: any other chest diseases. Previously diagnosed with dyslipidemia. & patients received therapy for lipids.

Methods
History taking, clinical examination, and laboratory investigation were done to all participants of the study.

Lipid profile
Fasting blood sample was obtained from all study individuals the day after admission. And serum levels of lipids were measured and compared between the cases and control groups. Blood samples were tested within one hour since they were taken from the patients or within 2 h when samples were been put in the refrigerator.
Pneumonia was diagnosed clinically by major criteria of infection (cough, sputum production, body temperature more than 37.8 °C) or two minor criteria (chest pain due to pleurisy, dyspnea, and pulmonary consolidation by examination), increase WBCS count of more than 10 3 / mm 3 , with consolidation in an x-ray, and radiologically by presence of opacity in chest x-ray which was diagnosed as bronchopneumonia or lobar pneumonia, also para pneumonic effusion detected in some cases as opacity obliterating costophrenic angle.

Results
This prospective study included 42 cases with pneumonia from the Chest Department of Menoufia University and El Mahalla Chest hospital (group A); in addition, a group of 10 healthy people was included as a control group (group B). In group A (patients), there were eighteen males (42.9%) and twenty-four females (57.1%) while in group B (controls), there were three (30%) males and seven (70%) females. In group A, the mean age of the patients was 51.07 ± 14.33 years and group B was 47.70 ± 15.78 years with no statistically significant difference between the two studied groups (p = O.516). The mean smoking index in group A was 458.8 ± 259.9 and group B was 275 ± 176.78 with no statistically significant difference between the studied groups (p = 0.35). The mean weight in group A was 72.8 ± 7.9 while in group B, it was 77.1 ± 8.7 (p = 0.769). The mean height in group A was 164.9 ± 6 and group B was 167.0 ± 7.70 (p = 0.424); the mean BMI in group A was 26.7 ± 2.9 and it was 26.9 ± 3.4 in group B (p = 0.714) with no statistical difference, as shown in Table 1.
The mean temperature in group A was 38.7 ± 1.77 which was higher than the mean temperature in group B (37.1 ± 0.37) with no statistical significance difference. The mean heart rate in group A was 98.72 ± 10.64 which was statistically significantly higher as compared with group B (89.90 ± 4.72) (p = 0.014). The mean respiratory rate in group A was 25.08 ± 2.95 which was statistically significantly higher as compared with group B (18.23 ± 5.60) (p = 0.015). The mean WBC count in group A was 14.67 ± 2.47 which was statistically significantly higher as compared with group B (9.46 ± 2.03) (p = 0.005). The mean neutrophil count in group A was 74.21 ± 13.35 which was statistically significantly higher as compared with group B (59.57 ± 6.25) (p = 0.021). The mean lymphocyte in group A was 19.52 ± 13.11 which was statistically significantly lower as compared with group B (26.94 ± 8.68) (p = 0.024). The mean NLR in group A was 7.04 ± 7.98 which was statistically significantly higher as compared with group B (3.04 ± 1.6) (p = 0.004), as shown in Table 2.
There was a significantly positive correlation between weight and N/L ratio (P = 0.008). Otherwise, no statistically significant differences were found (p > 0.05), as shown in Table 3.
In the Roc curve of N/L ratio in the case group, the cutoff point is 1.94, and N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity, as shown in Table 5 and Fig. 1.
The mean cholesterol level in group A was 149.76 ± 42.79 within the normal range but statistically significantly lower than group B (165.90 ± 45.50) (p = 0.039). The mean HDL level in group A was 43.16 ± 6.32 within the normal range which was statistically significantly lower than group B (50.51 ± 9.60) (p = 0.026). The triglyceride level, LDL level, and VLDL   Table 6). There was a significant difference between males and females regarding cholesterol levels but there was no statistically significant difference between males and females regarding the rest of the lipid profile. Cholesterol, HDL. and LDL levels were higher in females than in males (171.04 ± 47.4, 52.87 ± 12.12, and 104.03 ± 52.51 and 145.11 ± 33.26, 48.70 ± 7.09, and 102.54 ± 149.95, respectively). Triglyceride was higher in males than in females (112.16 ± 30.78 and 110.78 ± 39.63, as shown in Table 7).
There were negative correlations between HDL and age, weight, and BMI (− 0.166, − 0.095, and − 0.181, respectively) with no statistical significance difference, but there was a negative correlation with smoking index with statistical significance difference (− 0.181, p = 0.001). There were positive correlations between cholesterol and smoking index, weight, and BMI (0.792, 0.433, and 0.784, respectively) with statistical significance difference (p = 0.001, p = 0.004, and p = 0.001). There were positive correlations between triglyceride and smoking index, weight, and BMI (0.765, 0.434, and 0.784, respectively). There was a negative correlation between triglyceride and height (− 0.493, p = 0.001) with a statistical significance difference. There were positive correlations between LDL and smoking index, weight, and BMI (0.750, 0.422, and 0.789 and p = 0.001, p = 0.005, and p = 0.001, respectively) with statistical significance difference. There was a negative correlation between LDL and height (− 0.514) with a statistical significance difference (p = 0.001). There were positive correlations between V LDL and smoking index, weight, and BMI (0.776, 0.458, 0.799, respectively) with statistical significance difference (p = 0.001, p = 0.002, and p = 0.001). There was a negative correlation between VLDL and height (− 0.468) with a statistical significance difference (p = 0.002) as shown in Table 8.

Discussion
Pneumonia is an inflammation of the lungs that affects the alveoli or small air sacs. Cough, productive or dry, chest pain, fever, and dyspnea are common symptoms. The severity of the illness varies. Pneumonia is caused by either a viral or bacterial infection. It can be difficult to identify the causative agent. Diagnosis is based on symptoms and physical examination. Chest x-rays, blood tests, and sputum cultures can help confirm the diagnosis. Diseases can be categorized according to where they were obtained. Examples: community-acquired infections, nosocomial infections, or healthcare-associated pneumonia [1].
On laboratory investigations in the studied groups, our results reported that WBCs, neutrophil count, and NLR were statistically significantly higher in group A, while lymphocyte count decreases in group A than in group B with a statistically significant difference. In agreement,    [8][9][10][11].
In the present study, there was a positive non-significant correlation between N/L ratio and age either male or female, smoking index, and BMI. In our study, there was a significantly positive correlation between weight and N/L ratio (P = 0.008). There was a negative non-significant correlation between N/L ratio and height (p = 0.142) with no statistically significance difference. NLR was reported by de Jager et al. and Lee et al. as a marker of inflammation in cases with pneumonia [12,13].
Moreover, multiple cancer studies for survival mentioned by Sarraf et al. and Walsh et al. also mentioned that NLR is a significant predictor of overall and diseasespecific survival in patients [14,15].
As regards Roc curve of N/L ratio in the case group, we found that at cutoff point is 1.94, and N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity. Ge et al. mentioned that the AUC of NLR was   [16].
In the present study, there was positive non-significant relation between N/L ratio and smoking (p = 0.575). the same result was reported by Mukta Pujani et al. There was no significant difference in the NLR among the smokers and non-smokers (2.61 ± 1.99), (2.48 ± 2.30) respectively. [17].
In the present study, there was a positive significant difference between the mean N/L ratio and sex as it was 4.5 ± 2.8 and 10.4 ± 6.8 between males and females, respectively. On contrary to the present study, Lin BD et al. mentioned that women with lower mean NLR levels than men [18].
HDL and cholesterol levels decrease in group A with a statistically significant difference, while there was no statistically significant difference in the triglyceride level, LDL level, and VLDL between the subjects in the two study groups (p = 0.479, 0.792, and 0.606, respectively). In agreement with our study, Ko et al. found that a low level of total serum cholesterol at admission in the pneumonia group with a statically significant difference. In disagreement with our study, Chien et al. found that serum HDL, cholesterol, and LDL on admission had no significant difference between the two studied groups [19,20].
In our study, there were positive correlations between cholesterol, triglyceride, LDL, VLDL, and BMI (p = 0.001) with a statistically significant difference, while there was a negative correlation between HDL and BMI (r = − 0.181,  p = 0.250) with no statistically significant difference. According to Reddy RR and Nambiar S., it was observed that there was a positive correlation between TC, LDL, and BMI with a statistically significant difference [22].

Conclusion
There was a significant decrease in serum cholesterol and HDL in cases with pneumonia when compared to the control group but still within the normal range. Lipid profile is affected by different variables like smoking index, body mass index, and sex. The neutrophillymphocyte ratio (NLR) is a cheap diagnostic tool in the assessment of patients with pneumonia in daily practice at a cutoff point of 1.94 and N/L ratio with 79.6% sensitivity and 67.8% specificity.