Dataset Information

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

ABSTRACT:

Rationale

C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain.

Objectives

To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response.

Methods

We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE).

Measurements and main results

53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61-0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response.

Conclusions

Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes.

SUBMITTER: Sharma A

PROVIDER: S-EPMC5298271 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

Sharma Ashutosh A Kirkpatrick Gordon G Chen Virginia V Skolnik Kate K Hollander Zsuzsanna Z Wilcox Pearce P Quon Bradley S BS

PloS one 20170208 2

<h4>Rationale</h4>C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain.<h4>Objectives</h4>To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response.<h4>Methods</h4>We reviewed all PEx even ...[more]

PMID: 28178305

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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/.

Project description:Background and objectivesPulmonary exacerbations lead to significant morbidity and mortality in patients with cystic fibrosis (CF). National consensus guidelines exist, but few studies report current practice in the treatment and monitoring of pulmonary exacerbations. The goal of this study was to characterize consistency and variability in the inpatient management of CF-related pulmonary exacerbations. We focused on the use of guideline-recommended maintenance therapies, antibiotic selection and treatment regimens, use of systemic corticosteroids, and frequency of lung function testing. We hypothesized that significant variability in these treatment practices exists nationally.MethodsThis trial was a retrospective cross-sectional study. It included patients with CF aged ≤18 years hospitalized for pulmonary exacerbations between July 1, 2010, and June 30, 2015, at hospitals within the US Pediatric Health Information System database that are also Cystic Fibrosis Foundation-accredited care centers. One exacerbation per patient was randomly selected over the 5-year study period.ResultsFrom 38 hospitals, 4827 individual pulmonary exacerbations were examined. Median length of stay was 10.0 days (interquartile range, 6-14.0 days). Significant variation was seen among centers in the use of hypertonic saline (11%-100%), azithromycin (5%-83%), and systemic corticosteroids (3%-61%) and in the frequency of lung function testing. Four different admission antibiotic regimens were used >10% of the time, and the most commonly used admission antibiotic regimen comprised 2 intravenous antibiotics with no additional oral or inhaled antibiotics (29%).ConclusionsSignificant variation exists in the treatment and monitoring of pulmonary exacerbations across Pediatric Health Information System-participating, Cystic Fibrosis Foundation-accredited care centers. Results from this study can inform future research working toward standardized inpatient pulmonary exacerbation management to improve CF care for children and adolescents.

Project description:BackgroundEmerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints?Methods and findingsMulticentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire-Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049.ConclusionIn this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures.Clinical trial registrationNCT03000348; www.clinicaltrials.gov.

Dataset Information

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

Similar Datasets

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