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Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

ABSTRACT: Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity, and short-term and long-term outcome.Serum Igs were analyzed in blood samples obtained at admission and at 6 weeks postdischarge if admission levels were low. Serum complement deficiencies were screened with a total complement activity enzyme-linked immunosorbent assay (ELISA), with further analyzes performed if justified. Disease severity was assessed by the CURB-65 severity score. Short-term outcome was defined as a composite end point of intensive care unit (ICU) admission and 30-day mortality, and long-term outcome as 5-year all-cause mortality.At admission, 87 (34%) patients had low levels of at least 1 Ig, with low IgG2 as the most prevalent finding (55/21%). IgG levels were lower in bacterial than viral CAP (8.48 vs 9.97 g/L, P = .023), but low Igs were not associated with microbial etiology. Fifty-five (21%) patients had low lectin pathway activity, of which 33 (13%) were mannose-binding lectin (MBL) deficient. Low admission levels of any Ig or MBL were not associated with disease severity, short-term outcome, or long-term outcome. Excluding patients defined as immunocompromised from analysis did not substantially affect these results.In hospitalized adults with CAP, low admission levels of Igs or complement were in general not associated with microbial etiology, disease severity, short-term outcome, or long-term outcome.

SUBMITTER: Siljan WW

PROVIDER: S-EPMC5793818 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

Siljan William W WW Holter Jan C JC Nymo Ståle H SH Husebye Einar E Ueland Thor T Skattum Lillemor L Bosnes Vidar V Garred Peter P Frøland Stig S SS Mollnes Tom E TE Aukrust Pål P Heggelund Lars L

Open forum infectious diseases 20180105 2

<h4>Background</h4>Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity, and short-term and long-term outcome.<h4>Methods</h4>Serum Igs were analyzed in blood samples obtained at admission and at 6 weeks postdischar ...[more]

PMID: 29410975

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Project description:Community-acquired pneumonia (CAP) is a worldwide cause of morbidity and mortality. Immunoglobulins (Igs) and B cells quantification studies in CAP are few and show discrepancies. Serum IgA acts as a powerful natural anti-inflammatory factor, but its role in the CAP has not yet been defined. The highly sensitive xMAP Luminex technique allows better immunoglobulins quantification. The aim of this study was to analyze the relation between clinical severity and circulating Igs and B cells in adults with CAP.Igs (M, A, G1, G2, G3, and G4) and B cells were quantified in peripheral blood of 190 Chilean patients ≥18 years old hospitalized for CAP and in 21 adults without respiratory disease, using xMAP Luminex and flow cytometry, respectively. Clinical history was recorded and PSI and CURB-65 scores were calculated for evaluation of clinical severity.The total IgM, IgG2 and total IgG levels were lower in CAP than in asymptomatic adults (P < .05). No significant differences of Igs levels were found between patients classified as severe and mild by PSI and CURB-65 scores. Fatal cases had higher levels of IgA (P < .05). No differences in CD19 B cells frequency was found between CAP and asymptomatic adults (P = .40). In PSI severe cases, CD19 B cells were significantly lower than in mild cases (P = .008). No differences were found in CURB-65 severe and mild groups (P = .11). In fatal cases (11/82) group, CD19 B cells frequency was lower than in 71 survivors (P = .2). No differences in memory B lymphocytes were detected between asymptomatic and CAP adults, severe and mild patients, survivors and fatal cases (P > .05).Serum IgA levels were significantly higher in fatal CAP cases, raising it as a potential biomarker for severe disease considering its relatively universal availability. In PSI severe patients, B cells showed lower levels and could have a role on its physiopathology. Finding new markers rooted in physiopathology could improve the possibility of scoring severe CAP cases. Luminex technology showed promising quantification serum Igs.

Project description:Background:The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic treatment once a diagnosis of CAP is made. Concerns about treatment recommendations, on the one hand, and antibiotic stewardship, on the other, motivated this review of the medical literature on the etiology of CAP. Methods:We conducted a systematic review of English-language literature on the etiology of CAP using methods defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed using a combination of the keywords 'pneumonia', 'CAP', 'etiology', 'microbiology', 'bacteriology', and 'pathogen'. We examined articles on antibiotics that were develop to treat pneumonia. We reviewed all 'related articles' as well as studies referenced by those that came up in the search. After we excluded articles that did not give sufficient microbiological data or failed to meet other predetermined criteria, 146 studies remained. Data were stratified into diagnostic categories according to the microbiologic studies that were done; results are presented as the percentage in each category of all cases in which an etiology was established. Results:Streptococcus pneumoniae remains the most common cause of CAP although declining in incidence; this decline has been greater in the US than elsewhere. Haemophilus influenzae is the second most common cause of CAP, followed by Staphylococcus aureus and Gram negative bacilli. The incidence of all bacteria as causes of CAP has declined because, with routine use of PCR for viruses, the denominator, cases with an established etiology, has increased. Viruses were reported on average in about 10% of cases, but recent PCR-based studies identified a respiratory virus in about 30% of cases of CAP, with substantial rates of viral/bacterial coinfection. Conclusion:The results of this study justify current guidelines for initial empiric treatment of CAP. With pneumococcus and Haemophilus continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to the routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, allow for discontinuation of the antibiotic therapy.

Project description:Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12-24 h), Day 2 (at 36-48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6-1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.

Project description:BackgroundChildhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap.MethodsWe enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens.FindingsWe enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n?=?30) identified single pathogens in 10 (S. pneumoniae-3, CMV-3, S. aureus-2, H. influenzae-2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality.ConclusionsThe majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.

Dataset Information

Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

Publications

Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

Similar Datasets

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