Neural respiratory drive among patients with COPD with mild or moderate airflow limitation: consistency, reliability, and association with other biomarkers

Problem

Neural respiratory drive (NRD) is central control of breathing maintained through the respiratory muscles, particularly diaphragm and intercostals. It is closely correlated to the subjective measurement of breathlessness in asthmatic and COPD patients (stable state and during exacerbation). NRD has been measured by surface electromyography (EMG) of the second intercostal space parasternal muscles (EMGpara) predominantly among those COPD patients with severe or very severe airflow limitation. It has not previously been assessed in ambulatory patients with mild or moderate breathlessness in primary care. Its potential as a primary care research tool has not been evaluated.

This study aimed to assess the stability of NRD across a group of COPD patients with mild or moderate airflow limitation (FEV1 (forced expiratory volume in one second) ≥50% predicted) in primary care who were receiving treatment with inhaled corticosteroids (ICS). Relationships between NRD and changes in quality of life, lung function and breathlessness were assessed.

Approach

Patients with stable mild or moderate COPD were recruited from general practices. Second intercostal space NRD (EMG rms max; NRDI), spirometry, measures of breathlessness and quality of life (CRQ-SAS, mBorg, CAT, mMRC) were recorded at baseline, 3 and 6-month follow-up. Each patient was randomly allocated to continue using ICS (maintenance group) or to gradually withdraw ICS (initial withdrawal group) over 6 weeks. Intraclass correlation coefficients were calculated for each of the variables and Bland-Altman plots generated.

Findings

40 COPD patients with mild or moderate airflow limitation were recruited. There was high intra-rater and inter-rater agreement in each of the measures of NRD, including EMG rms max & NRDI (ICC > 0.9). There were moderate correlations between EMG rms max and FEV1% predicted (Pearson’s of r= -0.42; p=0.01) and between NRDI and FEV1% predicted (Pearson’s of r= -0.35; p=0.04). No correlation was seen between EMG rms max and any of CAT, CRQ domains, mBorg, or mMRC scores. No correlation was seen between NRDI and CAT, CRQ domains scores (except for Pearson’s of r= -0.42; p=0.01 between NRDI and CRQ mastery at 6 months assessment). Correlations were seen at baseline between NRDI & mBorg (Spearman’s rho 0.37, p=0.03), and at 6 months between NRDI & mMRC (Spearman’s rho 0.48, p=0.003). There were no consistent relationships between NRD readings and other measures of breathlessness.

Consequences

Assessment of NRD using surface electromyography had a moderate correlation with FEV1 but was not found in this study to be a sensitive measure of breathlessness in COPD patients with mild or moderate airflow limitation. The reliability of the recording in these patients and its established usefulness in assessing breathlessness in severe and very severe airflow limitation suggests that if the measurement can be made more sensitive it will be useful in interventional studies in primary care settings.