Predicted Reference Values

Predicted reference values assist in the interpretation of lung function results and are derived from equations determined by testing large populations of normal healthy individuals who are never smokers and working out the contribution (weighting) of different factors on lung function. They are usually determined by gender, age, height, ethnicity and sometimes weight.
Defining Normality
Many labs define the range of normality for spirometry as values higher than the 80% of the mean predicted value (MPV) for FEV1 and FVC. A more scientific approach is to define the normal range as the range in which we are confident that 95% of the population lies. The 95% confidence interval is defined by the mean and the standard deviation.
Lower Limit of Normal (LLN)
Establishing the LLN should be done by analyzing some measure i.e. FVC or FEV1 in healthy subjects and then determining the variability of that measurement. In clinical medicine the fifth percentile is often defined as the LLN because it represents the segment of healthy subjects farthest below the average even though subjects in the fifth percentile are healthy they are arbitrarily defined as “abnormal” for clinical purposes.
Some clinicians use a fixed percentage (measured value divided by the reference value x 100) of the reference value to determine the degree of abnormality and eighty percent (80%) is often used as the limit of normal. Unfortunately this method leads to errors because the variability around the predicted value is relatively constant in adults. In other words the scatter of normal values does not vary with the size of the predicted value.


The inserted figure illustrates why using fixed percentages such as 80% of the predicted can lead to misclassification and introduces both age and height biases. The shaded areas represent the “normal” range from 100% of the predicted value down to the fifth percentile. The dashed line shows a fixed percentage of the predicted in this case 80% as is sometimes used to represent the LLN.
In tall young subjects 80% of the predicted is often less than the fifth percentile; using 80% as the limit can allow a patient who really does have decreased lung function (in the fifth percentile or lower) to be misclassified as normal. This situation is a false negative result; the patient has disease but the test does not indicate abnormality.
Similarly an elderly patient who is short may have a lung function parameter than is less than 80% of the predicted but well within the statistically normal range (above the fifth percentile). This short elderly subject would be misclassified as having lung disease when in fact she is within the “normal” range (i.e. a false positive result).
A more statistically sound approach for classifying abnormality is to compute the z-score or standard deviation score (SDS). If lung function varies in a normal fashion the mean ± 1.96 standard deviations (SDs) defines the 95% confidence interval. Statistically, 95% of the healthy population falls within approximately 2 SDs of the mean. The remaining subjects fall into either the highest or lowest 2.5% of the distribution. For many pulmonary function variables, only the LLN (i.e. below the mean) is significant. The z-score or SDS can be calculated easily if the variability (residual standard deviation) of the reference population is known.



Normal predicted values for ventilatory function generally vary as follows
1. Sex - for a given height and age males have a larger FEV1 & FVC but a slightly lower FEV1/FVC
2. Age – After age 25 all indices gradually fall and the fall in FEV1/FVC is due to the greater decline in FEV1 than FVC although the precise rate of decline is probably masked due to the complex interrelationship between age and height.
3. Height – All indices other then FEV1/FVC increase with standing height
4. Ethnic Origin – Caucasians have the largest FEV1 & FVC of the various ethnic groups. Whilst Polynesians are among the lowest.
The purpose of reference values is to remove the variability in spirometry due to gender; age etc. and the reference source should be carefully considered and not left to equipment manufacturers but there are no universally accepted reference values. The major problem with many portable spirometers is that they report results as a percentage of predicted and do not include LLN.
We know that clinical decisions should be based on well-defined lower limits of normal rather than fixed percents of predicted (in adults) and to assist in the interpretation of our reports in our lab we have just introduced the LLN values to our suite of reports.

Vanessa