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Potential Biomarker Identified for Lung Disease in Cystic Fibrosis

Found in sputum, a microRNA cluster associated with pulmonary exacerbations could alert physicians early and guide treatment.

Patients with cystic fibrosis (CF) suffer from repeated pulmonary exacerbations, but there are no reliable biomarkers associated with the onset or progression of these episodes.

Some microRNAs, however, have the potential to be highly specific and sensitive biomarkers. Physicians and researchers at The Ohio State University and Nationwide Children’s Hospital led by Amal Amer, MD, PhD, identified a microRNA cluster, Mirc1/Mir17-92, playing a role regulating autophagy in mouse models of CF. Dr. Amer is a professor of Microbial Infection and Immunity at The Ohio State University College of Medicine.

Since this microRNA cluster was highly expressed in CF mice and appeared to negatively regulate autophagy, some of the same researchers recently examined its expression in human cells and fluids. The results suggest a future role for the microRNA cluster as a biomarker of pulmonary exacerbations and response to treatment. The findings were published in the Journal of Cystic Fibrosis.

The researchers found that Mirc1/Mir17-92 cluster expression was highly elevated in sputum from CF patients compared to controls. What’s more, cluster expression in sputum was positively correlated with pulmonary exacerbations and negatively correlated with lung function.

“Sometimes patients can have improved symptoms and not improved lung function or vice versa.”

– Benjamin Kopp, MD, MPH

Finding biomarkers that can indicate a pulmonary exacerbation at an early stage could help clinicians intervene and avoid further injury, and identify patients at risk for accelerated lung function deterioration.

Biomarkers could also help clinicians determine the optimal length of treatment of pulmonary exacerbations in CF patients, says Benjamin Kopp, MD, MPH, a member of the Section of Pulmonary Medicine at Nationwide Children’s, a principal investigator in the hospital’s Center for Microbial Pathogenesis and an author of the study.

“Sometimes patients can have improved symptoms and not improved lung function or vice versa,” says Dr. Kopp. “Biomarkers would help accurately determine when they start and resolve their exacerbation.”

The researchers also found that Mirc1/Mir17-92 cluster expression is not demonstrably changed by treatment with the CFTR modulator lumacaftor/ivacaftor. According to Dr. Kopp, this corroborates the lack of significant clinical improvement of some CF patients undergoing treatment with this drug combination. He says future studies will be needed to determine if Mirc1/Mir17-92 cluster expression could be a useful biomarker of response to other types of treatment.

“Ultimately, we’d like to predict exacerbations before they occur,” says Dr. Kopp. “That might require a combination of clinical factors and biomarkers.”

CITATION:
Krause K, Kopp BT, Tazi MF, Caution K, Hamilton K, Badr A, Shrestha C, Tumin D, Hayes D Jr, Robledo-Avila F, Hall-Stoodley L, Klamer BG, Zhang X, Partida-Sanchez S, Parinandi NL, Kirkby SE, Dakhlallah D, McCoy KS, Cormet-Boyaka E, Amer AO. The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients. Journal of Cystic Fibrosis. 2017 Dec 11. [Epub ahead of print]

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