scholarly journals Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haroon Arshad ◽  
Juan Carlos López Alfonso ◽  
Raimo Franke ◽  
Katina Michaelis ◽  
Leonardo Araujo ◽  
...  

Abstract Background There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. Results Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. Conclusions The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.

2020 ◽  
Vol 41 (06) ◽  
pp. 817-829
Author(s):  
Ernesto Crisafulli ◽  
Alessandra Manco ◽  
Miquel Ferrer ◽  
Arturo Huerta ◽  
Claudio Micheletto ◽  
...  

AbstractPatients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future.


2019 ◽  
Vol 91 (3) ◽  
pp. 42-45
Author(s):  
U R Farkhutdinov ◽  
E F Amirova ◽  
R R Farkhutdinov

Aim. The objective is to study clinical peculiarities, production of active oxygen forms and general antioxidant blood status in patients with community acquired pneumonia and in its combination with chronic obstructive pulmonary disease. Materials and methods. 59 patients hospitalized in patient department took part in the study. The first group included 32 patients with community acquired pneumonia (CAP).The second group included 27 patients with combination of community acquired pneumonia and chronic obstructive pulmonary disease (CAP+COPD). Symptoms of the disease, clinico-laboratory data and findings of the instrumental investigations were analyzed in the patients. Production of active oxygen forms (AOF) in the whole blood was studied. General antioxidant status (AOS) was analyzed in the blood serum. Results and discussion. The values of prognostic CRB-65 scale and clinical index of the severity of the condition were higher in patients with CAP+COPD compared to the patients with CAP. The reduction of spontaneous and induced by pyrogenal chemiluminescence (ChL) of blood has been found in the patients; this fact indicates decreased production of AOF by the cells. In patients with CAP general AOS of the blood was found to be increased but in patients with CAP+COPD it was decreased. After the course of treatment in patients with CAP+COPD symptoms of the disease remained, the level of C-reactive protein in serum was high and the level of AOS of blood was low, disturbances in the AOF production were observed. Conclusion. In patients with CAP+COPD in comparison with CAP patients the intensity of clinical symptoms was higher, the inflammatory process had a prolonged character, disturbances in the production of AOF and AOS of blood were more marked.


2017 ◽  
Vol 36 (2) ◽  
pp. 122-126 ◽  
Author(s):  
Ayfer Çolak ◽  
Celalettin Yılmaz ◽  
Burak Toprak ◽  
Serir Aktoğu

Summary Background: Serum procalcitonin (PCT) and C-reactive protein (CRP) are markers of systemic inflammation and bacterial infection. We aimed to compare the usefulness of procalcitonin and CRP in patients with communityacquired pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD). Methods: A total of 116 consecutive patients were included in the study: 76 with chronic obstructive pulmonary disease in group 1, and 40 with pneumonia in group 2. Results: Median serum CRP level was 44 mg/L in the COPD group and 132 mg/L in the pneumonia group. Median value of serum PCT was found to be 0.07 in the COPD group and 0.14 ng/mL in the pneumonia group. Serum PCT and CRP levels were significantly higher in the pneumonia group compared to the COPD group (p<0.001). The area under the ROC curve was 0.788 (Cl: 0.704-0.872) for CRP and 0.699 (Cl: 0.599-0.800) for procalcitonin to identify pneumonia. Conclusions: Procalcitonin and CRP levels were significantly higher in patients with community-acquired pneumonia presenting to the emergency department with indications for hospitalization than in patients with exacerbations of chronic obstructive pulmonary disease. Serum CRP and procalcitonin concentrations were strongly correlated. CRP might be a more valuable marker in these patients with lower respiratory tract infections.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Kek Pang ◽  
Ahmad Izuanuddin Ismail ◽  
Yoke Fun Chan ◽  
Adelina Cheong ◽  
Yoong Min Chong ◽  
...  

Abstract Background Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings. Methods We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018–August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis. Results Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January–February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329–0.970)], p = 0.038) and of dyspnea (0.544 (0.341–0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death). Conclusions Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population. Study registration, NMRR ID: NMRR-17-889-35,174.


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