Pulmonary biomarkers in COPD exacerbations: a systematic review.
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ABSTRACT:
SUBMITTER: Koutsokera A
PROVIDER: S-EPMC4014989 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA growing body of evidence suggests a role for oral bacteria in lung infections. This systematic review aimed to analyse the association between poor periodontal status and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations.MethodsPubMed, Embase, Web of Science, CINAHL and Medline were searched for studies published until May 2020, with no language restriction. Studies reporting periodontal condition, or periodontal treatment outcomes, with data on the frequency of exacerbations of COPD, were identified. The primary outcome was the frequency of exacerbations and secondary outcomes included quality of life (QoL) and hospitalisation. Quality and risk of bias assessment were carried out using the Newcastle Ottawa Scale for observational studies, Robins-1 tool for non-randomised intervention studies and Cochrane risk of bias assessment (RoB-2) tool for randomised clinical trials. Studies were assessed for eligibility and quality by two assessors independently.ResultsSearches identified 532 records and 8 met the inclusion criteria. Included studies were three clinical trials, one prospective cohort study, one case-control, and three cross-sectional studies. A narrative synthesis was performed. The data from intervention studies showed reduction in the frequency of exacerbations following periodontal treatment. Data from observational studies suggest association of worse plaque scores and fewer teeth with exacerbation, but not pocket depth or clinical attachment loss. Better periodontal health was also associated with reduced frequency of COPD exacerbations, hospitalisations and improved quality of life in COPD patients. Due to the high heterogeneity no meta-analysis was performed. The quality of some of the included studies was low and there was evidence of a high risk of bias.ConclusionThe data supports possible association between poor periodontal health, the frequency of exacerbations, hospitalisation and quality of life in COPD patients. The evidence is of moderate to low certainty and is limited by high risk of bias suggesting the need for well-designed and adequately powered randomised controlled trials, to inform future research and clinical practice. The PROSPERO registration number CRD42020180328.
| S-EPMC8418022 | biostudies-literature
Project description:IntroductionMetabolomics is an emerging area of research and has the potential to identify clinical biomarkers for predicting or diagnosing cystic fibrosis (CF) pulmonary exacerbations (PEx).ObjectiveTo identify clinically promising metabolites across different sample sources that can be used to predict or diagnose PEx in CF.Evidence reviewSearches for original literature were completed through EMBASE, MEDLINE, and all databases on the Web of Science with no restrictions on language or publication date. Gray literature was collected through Google Scholar. Additional studies were obtained by contacting authors and searching reference lists of candidate papers. The patient population included individuals with CF. Studies involving patients who underwent lung transplantation were excluded. The outcome was the prediction or diagnosis of pulmonary exacerbations from metabolites directly measured from biological samples. Search results were downloaded and imported into Covidence and duplicates were removed automatically. Any remaining duplicates were manually tagged and excluded. Two independent reviewers screened each abstract for eligibility and repeated this process for full texts. Risk of bias was conducted using QUADAS-2 by two independent reviewers. A third author resolved any remaining conflicts.ResultsA combined 3974 relevant abstracts were identified and 115 full texts were assessed for eligibility. The final 25 studies underwent data extraction for study design, patient demographics, studied metabolites, concentration values, and diagnostic accuracy values. Included studies differed considerably in methodologies, sample specimen types (exhaled breath condensate [EBC], sputum, saliva, plasma, urine), and disease states. We identified 19 unique metabolites that were measured by two or more studies of which 2 have the potential to predict PEx (EBC 4-hydroxycyclohexylcarboxylic acid [4-HCHC] and lactic acid) and 6 to diagnose PEx (EBC 4-HCHC and lactic acid, sputum lactic acid and nitrate, and plasma arginine and methionine).Conclusion and relevanceThis systematic review has identified promising metabolites for further study in CF. Certain metabolites may provide clinical potential in predicting or diagnosing PEx, but further validation studies are required. With better tools to aid in the earlier identification of PEx, clinicians can implement preventative measures to mitigate airway damage.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.
| S-EPMC9192952 | biostudies-literature
Project description:BackgroundPulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management. We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program. Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.MethodsWe identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.ResultsWe included 13 randomized trials (801 participants). Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [- 6.85 to - 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])). Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate. Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.ConclusionModerate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation. Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months. Therefore, we recommend early supervised PR to patients with COPD-related exacerbations. PR should be initiated during hospital admission or within 4 weeks after hospital discharge.
| S-EPMC6139159 | biostudies-literature
Project description:BACKGROUND:Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated. METHODS:The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD. Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition. RESULTS:Eighty-six patients (mean age, 72 years; male, 64%) were included. During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three. A dual infection was present in three patients. After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection. CONCLUSIONS:Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract. In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others. TRIAL REGISTRATION:clinicaltrials.gov; Identifier: NCT00448604.
| S-EPMC7094578 | biostudies-literature
Project description:BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated loss of lung function and death. Identification of patients at risk for these events, particularly those requiring hospitalization, is of major importance. Severe pulmonary hypertension is an important complication of advanced COPD and predicts acute exacerbations, though pulmonary vascular abnormalities also occur early in the course of the disease. We hypothesized that a computed tomographic (CT) metric of pulmonary vascular disease (pulmonary artery enlargement, as determined by a ratio of the diameter of the pulmonary artery to the diameter of the aorta [PA:A ratio] of >1) would be associated with severe COPD exacerbations.MethodsWe conducted a multicenter, observational trial that enrolled current and former smokers with COPD. We determined the association between a PA:A ratio of more than 1 and a history at enrollment of severe exacerbations requiring hospitalization and then examined the usefulness of the ratio as a predictor of these events in a longitudinal follow-up of this cohort, as well as in an external validation cohort. We used logistic-regression and zero-inflated negative binomial regression analyses and adjusted for known risk factors for exacerbation.ResultsMultivariate logistic-regression analysis showed a significant association between a PA:A ratio of more than 1 and a history of severe exacerbations at the time of enrollment in the trial (odds ratio, 4.78; 95% confidence interval [CI], 3.43 to 6.65; P<0.001). A PA:A ratio of more than 1 was also independently associated with an increased risk of future severe exacerbations in both the trial cohort (odds ratio, 3.44; 95% CI, 2.78 to 4.25; P<0.001) and the external validation cohort (odds ratio, 2.80; 95% CI, 2.11 to 3.71; P<0.001). In both cohorts, among all the variables analyzed, a PA:A ratio of more than 1 had the strongest association with severe exacerbations.ConclusionsPulmonary artery enlargement (a PA:A ratio of >1), as detected by CT, was associated with severe exacerbations of COPD. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov numbers, NCT00608764 and NCT00292552.).
| S-EPMC3690810 | biostudies-literature
Project description:RationaleAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.Materials and methodsSubjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman's correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters.ResultsA total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV1 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, P<0.001), pulmonary edema (AUC =0.63, P=0.009), and pleural effusion on CXR (AUC =0.64, P=0.01); whereas on CT images, NT-proBNP concentrations were associated with pleural effusion (AUC =0.71, P=0.002). Serum CRP concentrations, on the other hand, were associated with consolidation on CT images (AUC =0.75, P<0.001), ground glass opacities (AUC =0.64, P=0.028), and pleural effusion (AUC =0.72, P<0.001) on CT images. A serum CRP sensitivity-oriented cutoff point of 11.5 mg/L was selected for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which has a sensitivity of 91% and a specificity of 53% (P<0.001).ConclusionElevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.
| S-EPMC5764289 | biostudies-literature
Project description:The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications. Patients of interest were those that have been diagnosed with COPD. MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers. We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality. Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-?). CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-? had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance. Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts.
| S-EPMC4951145 | biostudies-literature
Project description:BackgroundThe majority of patients with chronic obstructive pulmonary disease (COPD) suffer from comorbid cardiovascular (CV) disease. Accumulating evidence suggests a temporal association between COPD exacerbations and acute CV events, possibly due to lung hyperinflation, increased hypoxemia and systemic inflammation. The aims of the study were to estimate the risk of (1) acute CV events [acute myocardial infarction (AMI), CV-related death] or stroke in the months following a COPD exacerbation and (2) COPD exacerbation in the months following an acute CV event.MethodsA systematic literature review of observational studies published since 2000 was conducted by searching literature databases (Medline and Embase). Studies were eligible if conducted in adults with COPD, exposed to either COPD exacerbation or acute CV events, with outcomes of acute CV events or COPD exacerbation reported. Studies were appraised for relevance, bias and quality. Meta-analyses, using random-effect models, were performed for each outcome of interest, thus providing a pooled relative risk (RR) and its 95% confidence interval.ResultsEight studies were identified, of which seven were used for the meta-analyses examining the risk of CV events 1-3 months after an exacerbation compared with none. For stroke (six studies), RR was 1.68 (95% CI = 1.19-2.38). For AMI (six studies), RR was 2.43 (95% CI = 1.40-4.20). No studies exploring risk of exacerbation following an acute CV event were identified.ConclusionThis meta-analysis identified a markedly increased risk of stroke or AMI within a relatively short period of time following a COPD exacerbation. Although the underlying mechanisms are not fully elucidated, patients with COPD should be monitored for risk of CV outcomes after exacerbations. In addition, preventing exacerbations may decrease the risk of subsequent acute CV events.RegistrationThe study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42020211055).
| S-EPMC9340406 | biostudies-literature
Project description:BackgroundReports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations. However, the magnitude of this reduction varies between studies.MethodElectronic databases were searched from January 2020 to May 2021. Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions. Exacerbation reduction was compared against the COVID-19 Containment and Health Index.ResultsA total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries. Nine studies could be included in the meta-analysis. The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57). Findings on the rate of community-treated exacerbations were inconclusive. Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period. There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).ConclusionThere was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations. Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period.
| S-EPMC8330941 | biostudies-literature
Project description:For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations.We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment.We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I(2) = 75%) [corrected] Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.038) [corrected] Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.81, 95% CI 0.55-1.18, I(2) = 13%) [corrected] Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16-0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3-5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06-0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12-30).Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients.
| S-EPMC1853091 | biostudies-other