Obstructive Lung Diseases: Airways 5 |

Metabolomics in COPD Acute Respiratory Failure FREE TO VIEW

Spyridon Fortis, MD; Elizabeth Lusczek; Craig Weinert, MD; Gregory Beilman, MD
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University of Minnesota, Minneapolis, MN

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):885A. doi:10.1016/j.chest.2016.08.985
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM

PURPOSE: Acute respiratory failure (ARF) due to COPD exacerbation causes distressing symptoms of severe dyspnea, is costly and decreases patients’ functional status long after hospital discharge. Severe airflow obstruction increases respiratory muscle workload and can lead to respiratory muscle fatigue, a cardinal feature of ARF. Biochemical changes associated with respiratory muscle fatigue and the high metabolic demand state in COPD with ARF have not well been studied. Early treatment of COPD exacerbations reduces hospitalization and improves health-related quality of life. Therefore, early diagnosis of COPD exacerbation when symptoms are mild or absent is critical. Since there are no objective biomarkers for COPD exacerbation, its diagnosis is based solely on clinical findings which may result in overtreatment. Many human diseases including COPD are associated with an abnormal metabolic state. Serum metabolic profiles correlate with severity of cachexia and obstruction in COPD. However, it is not known whether the transition from stable COPD to an exacerbation severe enough to require non-invasive positive pressure mechanical ventilation (NIPPV) is correlated with changes in the metabolic profile. Hypothesis: ARF in patients with COPD that require NIPPV is characterized by a unique metabolic profile in body fluids.

METHODS: We recruited adult subjects with moderate, severe or very severe but stable COPD from outpatient clinics. We also identified hospitalized patients with ARF due to COPD, CHF, and pneumonia (PNA) and enrolled them within 24 hours of NIPPV therapy. We excluded patients admitted with > 1 of the following diagnosis: COPD, CHF, PNA, patients with a history of both COPD and heart failure, and patients with obstructive sleep apnea, bronchial asthma, bronchiectasis or other obstructive lung disease. Serum and urine were collected from patients and metabolomics analysis was performed using nuclear magnetic resonance (NMR) in patient samples after adjustment for osmolality. Metabolites were identified and quantified with Chenomx software and the resulting profiles were analyzed for differences among patient groups with partial least squares discriminant analysis (PLS-DA).

RESULTS: We enrolled 15 subjects with stable COPD from the clinic and 29 hospitalized patients with ARF due to COPD (12), CHF (8), or PNA (9). Of the 6 hospitalized patients who died, 1 had COPD, 2 had CHF, and 3 had PNA. PLS-DA distinguished sera of patients with stable COPD from sera of patients with ARF due to COPD, ARF due to CHF, and ARF due to PNA (P=0.001). Similarly, PLS-DA distinguished the urine profiles of patients with stable COPD from those with ARF (P<0.001). Urine and serum citrate and several serum amino acids were primarily responsible for differentiating groups.

CONCLUSIONS: These differences in several amino acids concentrations in serum and urine and serum citrate support the observation that ARF patients are in a state of high metabolic demand.

CLINICAL IMPLICATIONS: Measurement of serum and urine metabolites can potentially serve as biomarkers of respiratory failure.

DISCLOSURE: The following authors have nothing to disclose: Spyridon Fortis, Elizabeth Lusczek, Craig Weinert, Gregory Beilman

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