Latent class analysis-based subgroups and response to corticosteroids in hospitalised community-acquired pneumonia patients: a validation study.
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ABSTRACT:
SUBMITTER: Wittermans E
PROVIDER: S-EPMC9986765 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Latent class analysis-based subgroups and response to corticosteroids in hospitalised community-acquired pneumonia patients: a validation study.
Wittermans Esther E van der Zee Philip A PA Qi Hongchao H Grutters Jan C JC Voorn G Paul GP Bos Willem Jan W WJW van de Garde Ewoudt M W EMW Endeman Henrik H
ERJ open research 20230306 2
<b>In patients with community-acquired pneumonia, LCA can identify robust prognostic subgroups based on clinical and inflammatory parameters. Yet, these subgroups have not proven robust in predicting response to adjunctive dexamethasone treatment.</b> https://bit.ly/3O5eaxz. ...[more]
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Project description:Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups. LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA. A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes. In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.
| S-EPMC8752939 | biostudies-literature
Project description: Not available
| S-EPMC5922336 | biostudies-literature
Project description:Community-acquired pneumonia is still a major cause of morbidity and mortality worldwide. Since the inflammatory response induced by the immune system is often a major contributor to the lung injury, it becomes reasonable to assess the potential benefit of anti-inflammatory agents in treating community-acquired pneumonia. The role of corticosteroids as adjunct anti-inflammatory agents in treating community-acquired pneumonia is still controversial. Several studies have assessed the benefit of their use in patients with community-acquired pneumonia. In most of those studies, the route of corticosteroids administration was systemic. The aim of this article is to provide a concise review of the role of corticosteroids in treating community-acquired pneumonia when administered via inhalational route, with the potential benefit of avoiding systemic side effects of corticosteroids while exerting the same anti-inflammatory effects on the lungs. Conclusion: the use of inhaled corticosteroids may be of benefit in certain patient subsets with community-acquired pneumonia. Further randomized controlled trials are needed for better determination of such patient subsets.
| S-EPMC8162532 | biostudies-literature
Project description:IntroductionInternational guidelines provide heterogenous guidance on use of corticosteroids for community-acquired pneumonia (CAP).MethodsWe performed a systematic review of randomized controlled trials examining corticosteroids in hospitalized adult patients with suspected or probable CAP. We performed a pairwise and dose-response meta-analysis using the restricted maximum likelihood (REML) heterogeneity estimator. We assessed the certainty of the evidence using GRADE methodology and the credibility of subgroups using the ICEMAN tool.ResultsWe identified 18 eligible studies that included 4661 patients. Corticosteroids probably reduce mortality in more severe CAP (RR 0.62 [95% CI 0.45 to 0.85]; moderate certainty) with possibly no effect in less severe CAP (RR 1.08 [95% CI 0.83 to 1.42]; low certainty). We found a non-linear dose-response relationship between corticosteroids and mortality, suggesting an optimal dose of approximately 6 mg of dexamethasone (or equivalent) for a duration of therapy of 7 days (RR 0.44 [95% 0.30 to 0.66]). Corticosteroids probably reduce the risk of requiring invasive mechanical ventilation (RR 0.56 [95% CI 0.42 to 74] and probably reduce intensive care unit (ICU) admission (RR 0.65 [95% CI 0.43 to 0.97]) (both moderate certainty). Corticosteroids may reduce the duration of hospitalization and ICU stay (both low certainty). Corticosteroids may increase the risk of hyperglycemia (RR 1.76 [95% CI 1.46 to 2.14]) (low certainty).ConclusionModerate certainty evidence indicates that corticosteroids reduce mortality in patients with more severe CAP, the need for invasive mechanical ventilation, and ICU admission.
| S-EPMC10115386 | biostudies-literature
Project description:Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I(2) statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.
| S-EPMC4571641 | biostudies-other
Project description:ObjectiveTo identify aetiologies of childhood community-acquired pneumonia (CAP) based on a comprehensive diagnostic approach.Design'Partnerships for Enhanced Engagement in Research-Pneumonia in Paediatrics (PEER-PePPeS)' study was an observational prospective cohort study conducted from July 2017 to September 2019.SettingGovernment referral teaching hospitals and satellite sites in three cities in Indonesia: Semarang, Yogyakarta and Tangerang.ParticipantsHospitalised children aged 2-59 months who met the criteria for pneumonia were eligible. Children were excluded if they had been hospitalised for >24 hours; had malignancy or history of malignancy; a history of long-term (>2 months) steroid therapy, or conditions that might interfere with compliance with study procedures.Main outcomes measuresCausative bacterial, viral or mixed pathogen(s) for pneumonia were determined using microbiological, molecular and serological tests from routinely collected specimens (blood, sputum and nasopharyngeal swabs). We applied a previously published algorithm (PEER-PePPeS rules) to determine the causative pathogen(s).Results188 subjects were enrolled. Based on our algorithm, 48 (25.5%) had a bacterial infection, 31 (16.5%) had a viral infection, 76 (40.4%) had mixed bacterial and viral infections, and 33 (17.6%) were unable to be classified. The five most common causative pathogens identified were Haemophilus influenzae non-type B (N=73, 38.8%), respiratory syncytial virus (RSV) (N=51, 27.1%), Klebsiella pneumoniae (N=43, 22.9%), Streptococcus pneumoniae (N=29, 15.4%) and Influenza virus (N=25, 13.3%). RSV and influenza virus diagnoses were highly associated with Indonesia's rainy season (November-March). The PCR assays on induced sputum (IS) specimens captured most of the pathogens identified in this study.ConclusionsOur study found that H. influenzae non-type B and RSV were the most frequently identified pathogens causing hospitalised CAP among Indonesian children aged 2-59 months old. Our study also highlights the importance of PCR for diagnosis and by extension, appropriate use of antimicrobials.Trail registration numberNCT03366454.
| S-EPMC9214401 | biostudies-literature
Project description:Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.
| S-EPMC7173092 | biostudies-literature
Project description: Not available
| S-EPMC1718998 | biostudies-literature
Project description:BackgroundA short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP.MethodsThe patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score.ResultsThe percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness.ConclusionThe newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.
| S-EPMC1747065 | biostudies-literature
Project description:ObjectiveCommunity-acquired pneumonia (CAP) is a leading cause of hospitalisation in older adults and is associated with a high likelihood of adverse outcomes. Given the ageing population and lack of therapeutic advances in CAP, new strategies to manage the burden of this disease are needed. Neutrophil dysfunction has been widely demonstrated in CAP and is associated with poor outcomes. We hypothesised that impaired glycolytic metabolism was driving neutrophil dysfunction in older adults with CAP.MethodsTo investigate the mechanism underlying neutrophil dysfunction in CAP, we recruited older adults with CAP and sepsis, age-matched controls and healthy young adults to assess neutrophil function and glycolytic metabolism in peripheral blood neutrophils.ResultsWe demonstrate that neutrophils from older donors with CAP display a broad range of functional defects, including inaccurate migration to interleukin 8, impaired respiratory burst in response to phorbol 12-myristate 13-acetate and increased spontaneous degranulation compared with age-matched controls. Glycolysis (assessed by extracellular flux and RNA-sequencing) was not significantly altered between age-matched groups; however, basal rates of neutrophil glycolysis were significantly higher in patients with CAP and older adult controls compared with healthy young adults, and stimulated glycolysis was significantly higher in young adults compared with older adults with and without CAP.ConclusionsOur findings suggest that neutrophil dysfunction in older adults with CAP may be implicated in poor outcomes, irrespective of glycolytic metabolism.
| S-EPMC11877105 | biostudies-literature