Long Term Erythromycin and COPD - Online Supplement

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LONG TERM ERYTHROMYCIN THERAPY IS ASSOCIATED WITHDECREASED COPD EXACERBATIONS

Terence A. R. Seemungal*, Tom M.A. Wilkinson

†

John R Hurst

†

Wayomi R Perera

†

, Ray JSapsford

†

, Jadwiga A. Wedzicha

†

.

†

Academic Unit of Respiratory Medicine, University College London, London, UK, and*Department of Clinical Medical Sciences, St. Augustine Campus, University of the WestIndies.

Online Data Supplement

Methods

The QT interval on the electrocardiogram (ECG) is defined as the time between the startof the Q wave on the ECG and the end of the T wave. The RR interval is defined as theinterval between the onset of one QRS complex and the next QRS complex. Thecorrected QT interval (QTc) was calculated using Bazett’s formula (1) as the ratio of themeasured QT interval in milliseconds to the square root of the RR interval. The normalrange was taken as less than or equal to 440 milliseconds.

Statistical Analysis

We examined further the application of the Poisson regression to the exacerbationfrequency data. The standardized deviance residuals of the Poisson regression werecompared with the predicted values of the linear predictor. There appeared to be somerelation between the two and we concluded that variability in the dependent variable maybe related to the linear predictor. We next tested the goodness of fit for the Poissonregression using the Log likelihood test which was -201.389 which was less that thatusing a negative binomial regression (with chosen value of 1 for the ancillary parameter),goodness fit test was -188.396. We thought then that the negative binomial regressionmight offer some improvement on the Poisson Regression for our data. But the chosenvalue of '1' for the ancillary parameter in the negative binomial regression may not beoptimal for this distribution. Therefore we repeated the negative binomial analysis using

the Lagrange multiplier test. However when we did this there was no significant result forthe ancillary parameter (p = 0.080). We therefore concluded that overdispersion may notbe problem for the Poisson regression model we used. Thus we presented our resultsusing the Poisson regression as shown in the paper.

Results

Inflammatory Marker Change at (Sampled) ExacerbationsThere were 129 sampled exacerbations (87 on placebo and 42 on macrolide) of which 56(35 on placebo; 21 macrolide) were first exacerbations and the remainder were repeatedexacerbations in the same patients. Linear mixed models analysis showed that there was nodifference in estimated marginal means in FEV1, sputum IL6 or sputum IL8 betweenbaseline and first exacerbation, p > 0.05 in all cases. However baseline vs. first exacerbation(N = 56) mean (SE) serum CRP was 7.5(0.7) mg/L (baseline) vs. 19.0 (4.0) mg/l (firstexacerbation), p = 0.004; serum IL6 6.0(1) vs. 12.8 (2.7) pg/ml, p = 0.026; sputum MPO11.2(1.8) ng/ml vs. 22.1(4.9) ng/ml , p = 0.043 respectively. Thus there was elevation inserum CRP, serum IL6 and sputum MPO between baseline and first exacerbation. Howeverthere was no difference between drug and placebo arms in changes n sputum inflammatorymarkers at first exacerbation as shown in Table E1.References1. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920;7: 353–370.

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