Reference values for lung function: past, present and future

Abstract

Reliable interpretation of pulmonary function results relies on the availability of appropriate reference data to help distinguish between health and disease and to assess the severity and nature of any functional impairment.The overwhelming number of published reference equations, with at least 15 published for spirometry alone in the past 3 yrs, complicates the selection of an appropriate reference. The use of inappropriate reference equations and misinterpretation, even when potentially appropriate equations are used, can lead to serious errors in both under and over diagnosis, with its associated burden in terms of financial and human costs.Further misdiagnosis occurs when fixed cut-offs, such as 80% predicted forced expiratory volume in 1 s (FEV1) or 0.70 FEV1/forced vital capacity, are used; particularly in young children and elderly adults. While per cent predicted has historically been used to interpret lung function results, z-scores are more appropriate as they take into account the predicted value, as well as the between-subject variability of measurements.We aim to highlight some of the main issues in selecting and using reference equations and discuss how recent developments may improve interpretation of pulmonary function results.

New reference equations to improve interpretation of infant lung function

“…IPF z-scores were calculated as the difference between observed measurements and the predicted value divided by the RSD. 30 Data storage and management were undertaken using ReBase TM software (Re-Base Ltd., London, UK). All estimates are presented with 95% confidence intervals (CI).…”

“…By collating data from 153 white infants studied on up to 218 occasions, it was possible to derive prediction equations for a wide range of infant lung function outcomes, together with reliable estimates of the limits of normal to take expected between-subject variability at different ages and according to outcome into account. 30 These reference equations will be applicable to white children of European descent aged 0-2 years, with crown-heel length between 52 and 90 cm, who are studied using standardized protocols and the Jaeger MasterScreen BabyBody.…”

“…40 It will be important over the coming years to validate these equations using data collected in other centers, with subsequent amendments if required. 30 In addition, given the relatively low sample size, there will be a certain degree of imprecision around the calculated centiles. As an example, for a child in the mid-range of the dataset ($75 cm) the estimated 2.5th (95th CI) centile for FRC p would be 124 (116-132) ml, whereas at the extreme of the length range, these estimates would be 35(19-51) ml in a child of 55 cm length and 190 (175-205) ml in one who was 90 cm (see online data supplement E- Figure 1).…”

“…30 As such we did not exclude those with a family history of asthma or who had been exposed to tobacco smoke, both of which are common in the general population. In large epidemiological studies, such factors have been associated with reduced forced expiratory flows and increased plethysmographic airways resistance 31,32 but were not found to impact on the outcomes examined in this study.…”

Airflow limitation by the Global Lungs Initiative equations in a cohort of very old adults

“…Yet, in their guidelines for the interpretation of lung function tests, ATS/ERS support the use of the lower limit of normal (LLN) at the 5th percentile of the frequency distribution of values of a reference "healthy" never-smoker population of equivalent age and sex. The fixed cut-off approach leads to overdiagnosis of COPD in older adults, as it does not take into account the age-related decline in respiratory parameters, while the LLN cut-off approach is dependent on age-specific reference values [5,6]. These have been lacking for adults aged >80 years or have been extrapolated from younger populations, until recently when the Global Lungs Initiative (GLI) all-age reference equations for different ethnic groups and populations aged 3-95 years were made available [5,7].…”