GOLD v LLN    Page 2

Secondly the use of a single cut off for FEV1/FVC of 0.7 to define the limit of normality for this index is also not supported by the ATS or ERS [4, 5]. The fact that the arbitrary definition may lead to an age bias in the diagnosis of COPD has already been presented [6] and we will now explore the reason behind this in more detail.

Why is the LLN set at 1.645 SR below predicted?

Plot of normal distribution with LLN indicated

The figure to the right shows a plot of the FEV1 values from a sample population of normal men of the same age and height with the average value found being 3.5 L and the standard deviation of the spread of results is 0.5 L. For a subject with FEV1 of 2.678 L this is 1.645 SD below the predicted mean, that is 3.5 - (1.645 x 0.5), and means that 5% of the normal population have FEV1 values lower than this. The grey shaded area in the graph is 5% of the total area under the graph.

If we define the Lower Limit of Normal (LLN) as 1.645 SD below the predicted in effect we are accepting a false positive rate of 5% in identifying subjects as abnormal. Most subjects referred for spirometry have an a priori increased probability of an abnormality because of either symptoms, signs or exposures so the lower 95% confidence limit is used as the LLN. This increases the sensitivity of the test with some loss of specificity. If spirometry is being undertaken on people where the a priori probability of an abnormality is not increased, such as screening the general population, we should take the LLN as 1.96 SD below predicted and only accept a false positive rate of 2.5%. The ATS and ERS endorse using the LLN as 1.645 SD below predicted [4, 5].