Measurement of Serum Calprotectin in Stable Patients Predicts Exacerbation and Lung Function Decline in Cystic Fibrosis

Reid, Peter; McAllister, David A; Boyd, Alan; Innes, J A; Porteous, David J.; Greening, A P; Gray, Robert D.

doi:10.1164/rccm.201407-1365le

Cited by 43 publications

(34 citation statements)

References 15 publications

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“…A key next step will be to determine whether monitoring circulating proteins, including their integration in a clinical trial of CF pulmonary exacerbations, improves health outcomes beyond traditional symptom assessment and lung function testing. Systemic markers of inflammation may also prove to be valuable in predicting key clinical events in CF, including lung function decline, future pulmonary exacerbations, and possibly survival (36). n Author disclosures are available with the text of this article at www.atsjournals.org.…”

Section: O2 Saturationmentioning

confidence: 99%

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

et al. 2015

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Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation.Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement.Methods: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older.Measurements and Main Results: Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and a 1 -antitrypsin (a1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV 1 ). Baseline IL-8, neutrophil elastase antiprotease complexes, and a1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV 1 at exacerbation onset, were predictive of being a treatment responder. Conclusions:Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community.

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Section: O2 Saturationmentioning

confidence: 99%

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

et al. 2015

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“…In their study, there was a trend (not significant) for high CRP levels to be associated with a high risk of PExs. Reid et al [8] recently studied 57 adult patients with CF. They showed that in stable patients, serum calprotectin levels at baseline predicted future exacerbations in terms of a shorter time to the next exacerbation.…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein in Stable Cystic Fibrosis: An Additional Indicator of Clinical Disease Activity and Risk of Future Pulmonary Exacerbations

et al. 2016

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IntroductionIn stable adult cystic fibrosis (CF) patients, we assessed the role of baseline high sensitivity C-reactive protein (hs-CRP) on CF clinical variables and frequency of intravenous (IV) treated pulmonary exacerbations (PExs) 1-year post-baseline.MethodsWe recruited 51 clinically stable CF patients from our Adult CF Center. We incorporated collected parameters into Matouk CF clinical score and CF questionnaire-revised quality of life score (QOL). We used the clinical minus complications subscores as a clinical disease activity score (CDAS). We dichotomized our patients according to the cohort median baseline hs-CRP of 5.2 mg/L.ResultsPatients in the high hs-CRP group (≥ 5.2 mg/L) demonstrated worse CDAS (r=0.67, p=0.0001) and QOL scores (r=0.57, p=0.0017) at a given FEV1% predicted. In both hs-CRP groups, prior-year IV-treated PExs and baseline CDASs were significant predictors of future IV-treated PExs. Interestingly, the association between baseline CDAS and future PExs frequency was more robust in the high compared to the low hs-CRP group (r=−0.88, p<0.0001, r=−0.48, p=0.017, respectively) with a steeper regression slope (p=0.001). In addition, a significant interaction was demonstrated between elevated baseline hs-CRP levels and CDASs for the prediction of increased risk of future PExs (p=0.02). This interaction provided an additional indicator of clinical disease activity and added another dimension to the prior year PExs frequency phenotype to identify patients at increased risk for future PExs.ConclusionStable CF patients with elevated baseline hs-CRP (≥ 5.2 mg/L) demonstrated worse clinical disease activity and QOL scores at a given level of disease severity (FEV1% predicted). Elevated baseline hs-CRP values combined with clinical disease activity scores are associated with increased risk for future IV-treated PExs even in those with mild clinical disease activity scores.

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“…A single measurement of serum calprotectin, a neutrophil protein marker of inflammation, in stable patients with CF predicted the time to next exacerbation and decline in lung function; higher calprotectin levels were associated with worse outcomes . A retrospective study of patients with CF 5–22 years of age showed that lower serum 25‐OH Vitamin D level and female sex were strong independent determinants of the annual number of PEx ( P < 0.01) .…”

Section: Pulmonary Exacerbationsmentioning

confidence: 99%

Pediatric Pulmonologyyear in review 2015: Part 4

Savant

McColley

2016

Pediatr Pulmonol.

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Measurement of Serum Calprotectin in Stable Patients Predicts Exacerbation and Lung Function Decline in Cystic Fibrosis

Cited by 43 publications

References 15 publications

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

C-Reactive Protein in Stable Cystic Fibrosis: An Additional Indicator of Clinical Disease Activity and Risk of Future Pulmonary Exacerbations

Pediatric Pulmonologyyear in review 2015: Part 4

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