Published Reference Equations Research Articles

Development and validation of reference equations for dual-energy X-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free mass (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy X-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85 years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted aka index (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1881 healthy participants (57% male) aged 55 [IQR: 50-61] years. Reference equations performed comparably in the validation cohort and discriminated reference values between ostensibly healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years, although additional validation may be required for those>75 years.

Using reference equations to standardise incremental shuttle walk test performance in children and young people with chronic conditions and facilitate the evaluation of exercise capacity and disease severity

AimsThe aim was to evaluate whether standardised exercise performance during the incremental shuttle walk test (ISWT) can be used to assess disease severity in children and young people (CYP) with...

The modified Medical Research Council scale misclassifies exertional breathlessness among people referred for exercise testing.

Exertional breathlessness is a major symptom in cardiorespiratory disease and is often assessed using the modified Medical Research Council (mMRC) questionnaire. The mMRC might underestimate exertional breathlessness in people with impaired exercise capacity who have reduced their physical activity to avoid the symptom. We aimed to evaluate the ability of mMRC to detect abnormally high exertional breathlessness or abnormally low exercise capacity during incremental cycle exercise testing (IET). A secondary analysis of data from a randomised controlled trial of outpatients aged 18 years or older referred for IET was carried out. Participants completed the mMRC before IET. Abnormally high exertional breathlessness was defined as a breathlessness (Borg 0-10) intensity response more than the upper limit of normal. Abnormally low exercise capacity was defined using published reference equations. The sensitivity, specificity, accuracy and discriminative ability of each mMRC rating to detect each outcomewas calculated. 92 participants were included; the mean age was 59 years, 61% were male, and 64% and 15% had mMRC 1 and ≥2, respectively. An mMRC ≥2 had the highest accuracy (71%) to detect abnormally high exertional breathlessness, with a specificity of 93% but a sensitivity of only 28%, failing to identify 72% of people with abnormally high exertional breathlessness. The accuracy, specificity and sensitivity for abnormally low exercise capacity was 64%, 88% and 19%, respectively. Among people referred for clinical exercise testing, the mMRC dyspnoea scale misclassified exertional breathlessness and exercise capacity assessed using cycle IET, with substantial underdetection. A mMRC dyspnoea rating of 0-1 does not preclude the presence of abnormally high exertional breathlessness or abnormally low exercise capacity.

Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years.

Published reference equations for impulse oscillometry (IOS) usually encompass a specific age group but not the entire lifespan. This may lead to discordant predicted values when two or more non-coincident equations can be applied to the same person, or when a person moves from one equation to the next non-convergent equation as he or she gets older. Thus, our aim was to provide a single reference equation for each IOS variable that could be applied from infancy to old age. This was an ambispective cross-sectional study in healthy nonsmokers, most of whom lived in Mexico City, who underwent IOS according to international standards. A multivariate piecewise linear regression, also known as segmented regression, was used to obtain reference equations for each IOS variable. In a population of 830 subjects (54.0% female) aged 2.7 to 90 years (54.8% children ≤12 years), segmented regression estimated two breakpoints for age in almost all IOS variables, except for R5-R20 in which only one breakpoint was detected. With this approach, multivariate regressions including sex, age, height and body mass index as independent variables were constructed, and coefficients for calculating predicted value, lower and upper limits of normal, percentage of predicted and z-score were obtained. Our study provides IOS reference equations that include the major determinants of lung function, i.e. sex, age, height and body mass index, that can be easily implemented for subjects of almost any age.

Reference values and equations for the 6-minutewalk distance of Nigerian children aged 6-11 years: A cross-sectional study.

The 6-minutewalk test (6MWT), a simple, reliable, and valid test that uses the distance walked in 6 minute walk distance(6MWD) to quantify functional capacity, is widely used in the management of chronic disorders. However, the absence of reference standards from sub-Saharan African, including Nigerian, school-aged children limits its utility in this age group. To develop normative values and equations for the 6MWD of school-aged Nigerian children. In a cross-sectional study, healthy children aged 6-11 years in Lagos, Nigeria, completed the 6MWT on 20-m-long straight outdoor courses in their schools. The primary outcome was the 6MWD in meters while potential predictors included demographic (age, sex), anthropometric (height, weight, chest circumference, leg length) and physiologic variables (pre-walk, immediate post-walk, and fifth min-post-walk heart rate [HR], oxygen saturation [SpO2 ], systolic blood pressure [SBP], diastolic blood pressure [DBP], and rating of perceived exertion [RPE]; and the difference between pre-walk and post-walk HR [∆HR], SpO2 [∆SpO2 ], SBP [∆SBP], DBP [∆DBP], and RPE [∆RPE]). Overall, 627 pupils (52.1% girls) walked 504.6 ± 66.6 m (95% CI: 499.4, 509.8; range: 326.6-673.0 m); 16 m longer in boys (p = 0.002). A stepwise linear regression model yielded: 6MWD (m) = 347.9 + 14(Ageyears ) + 1.6 (∆HRbeats/min ) + 17.6(Sexmale=1, female=0 ) + 1.2(∆SBPmmHg ); R2 = 0.25. Previously published reference equations mostly over-estimated Nigerian children's 6MWD. These reference standards add to the global normative data on pediatric 6MWTand may be useful for the functional evaluation of Nigerian school-aged children with chronic childhood disorders.

Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies

During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001). If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.

Limitations of 6-minute walk test reference values for spinal muscular atrophy.

The 6-minute walk test (6MWT) is a well-established clinical assessment of functional endurance, validated as a measure of walking ability in spinal muscular atrophy (SMA). The current availability of disease-modifying therapies for SMA indicates a growing need for normative reference data to compare SMA patients with healthy controls. The literature was searched in two scientific databases. Studies were evaluated and selected based on adherence to American Thoracic Society guidelines for administering the 6MWT. Reference equations from the selected studies were applied to 6MWT data collected from SMA patients to calculate and compare % predicted values. Three pediatric and six adult studies were selected for comparison. The % predicted values using the pediatric and adult equations ranged from 47.7 ± 18.2% to 67.6 ± 26.2% and 43.0 ± 17.9% to 59.5 ± 26.2%, respectively, and were significantly different (P < 0.001). Results suggest significant variability between % predicted values derived from published reference equations in children and adults, despite adherence to 6MWT standardization.

Forced expiratory flows and volumes in a Swedish cohort of healthy term infants.

The use of pulmonary function tests (PFTs) in infants has increased during the last decades, making the need for equipment- and ethnic-specific reference data mandatory for appropriate interpretation of the results. Our aim was to investigate how well the already published reference equations for infant spirometry fit a healthy population of Swedish infants. We performed forced tidal and raised volume expiratory maneuvers in healthy infants using Jaeger BabyBody equipment. PFT data were collected from 91 healthy infants aged between 3 months to 2 years at 143 occasions. Mean (standard deviation) z-scores were 0.68(1.33) for maximal flow at functional residual capacity (V'max FRC), -0.15(0.96) for forced vital capacity (FVC), 0.40(1.33) for the forced expired volume in the initial 0.5 seconds (FEV0.5 ) and 0.52(0.93) for the ratio FEV0.5 /FVC, respectively. Z-scores for all indices but FEV0.5 /FVC were highly dependent on length. We have shown that the use of previously published reference equations may result in an age-related misinterpretation of lung function measure in a Swedish infant population.

Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant Have Reduced Six-Minute Walk Test Distance and Results Predict Transplant Outcomes

Introduction Impaired functional status is associated with poor outcomes following hematopoietic stem cell transplant (HSCT), but functional testing in pediatric patients is limited. Six-minute walk test (6MWT) predicts mortality in multiple adult diseases. We investigated whether pre-HSCT six-minute walk test (6MWT) distance was feasible in children and associated with outcomes post-HSCT. Methods We performed a retrospective chart review of all pediatric and young adult patients receiving HSCT at our center from June 2016 to September 2017 who were prospectively screened for pulmonary function per our clinical protocol. Patients over 3 years of age underwent pre-HSCT 6MWT using standard American Thoracic Society Criteria with age adjusted standard deviation (z-score) determined using published reference equations. Data presented as mean +/- standard deviation with p Results Twenty-seven patients, ages 11.0 +/- 6.3 years (range 3.8 – 25.8), completed pre-HSCT 6MWT 40.4 +/- 36 days before HSCT walking 1380 +/- 325 feet. Eight (29.6%) patients died during the study period. Age adjusted z-scores were significantly reduced (-2.94 +/- 2.2, p Conclusions 6MWT can be completed in patients as young as 3 years undergoing HSCT. Patients undergoing HSCT have significantly lower performance than age matched peers, even patients with high KLP status and reduced performance predicted subsequent poorer outcomes. 6MWT may provide additional insights into patient functional status going into HSCT.

Reference equations for the interpretation of forced expiratory and plethysmographic measurements in infants.

Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.

Respiratory function in healthy Emirati children using forced oscillations.

The forced oscillation technique (FOT) allows the quantification of respiratory function, does not require active cooperation and as such is ideally suited for use in young children. The application of the FOT in non-Caucasian populations is limited and it remains unclear if current reference ranges for the FOT in Caucasian children are appropriate for children in the Arabian Peninsula. This study explored the use of the FOT in healthy school-aged children in the United Arab Emirates (UAE). Lung function using FOT was assessed in healthy Emirati children aged 4-12 years. Using a validated questionnaires general medical and respiratory histories were obtained. Prediction equations for resistance (Rrs), reactance (Xrs), and area under reactance curve (AX) were calculated and compared to previous studies. FOT was successfully obtained in 291 healthy Emirati children. Linear regression modelling including weight, height, age, and gender in transformed FOT outcomes demonstrated that height was the strongest predictor of FOT outcomes (P < 0.001). Using the equated prediction equation Z-scores were calculated. FOT outcomes in Emirati children did not match previously published reference equations in Caucasians children (P < 0.001). FOT measurements were feasible in Emirati school-children. New FOT reference equation in Emirati children were derived. FOT reference equation in Emirati children was different from published equations in Caucasians.

Association between peripheral airway function and neutrophilic inflammation in asthma.

Small airway dysfunction is associated with asthma severity and control, but its association with airway inflammation is unknown. The aim was to determine the association between sputum inflammatory cells and the site of small airway dysfunction, measured by multiple breath nitrogen washout in convection-dependent (Scond) and more peripheral diffusion-dependent (Sacin) airways. Fifty-three (20-67 years) subjects with asthma on inhaled corticosteroid (ICS) treatment were characterized by spirometry, Scond, Sacin and induced sputum differential counts. %Predicted values for Scond and Sacin were calculated from published reference equations to adjust for the effects of age. Univariate correlations were assessed using the Spearman test. Multivariate linear regressions were performed to account for potential confounders, including age, gender, disease duration, body mass index and ICS dose. Sacin (%predicted) correlated significantly with neutrophil% (rs = 0.33, P = 0.02), ICS dose (rs = -0.28, P = 0.04) and age (rs = 0.27, P = 0.05). In multivariate analysis, Sacin related only to neutrophil% (adjusted R(2) = 0.18, P = 0.001). Scond (%predicted) correlated significantly only with eosinophil% (rs = 0.39, P = 0.004). There was a trend for a negative relationship with ICS dose (rs = -0.26, P = 0.06). In multivariate analysis, Scond related to eosinophil% and ICS dose independently (adjusted R(2) = 0.12, P = 0.02). Acinar and conductive airway dysfunction is associated with different inflammatory profiles in asthmatic airways, independently of the effects of age and disease duration. The association between acinar airway dysfunction and neutrophilic airway inflammation may have implications for asthma treatment.

Estimated lung age in healthy North African adults cannot be predicted using reference equations derived from other populations

IntroductionInterpretation of “lung age” data relies upon comparison of the chronological lung age (CLA) with the estimated lung age (ELA) predicted from published reference equations [7–10]. AimTo test the applicability of the published reference equations in healthy non-smoker Tunisian aged 19–90years. Population and methodsPublished reference equations were applied to the spirometry results of 540 adults (364 women). Two methods of comparison were applied: (i) Determination, according each equation, of the percentages of subjects having a deltaLungAge (=ELA–CLA)>Upper-Limit-of-Normal (ULN). (ii) Bland and Altman comparison, for the same age range as in the corresponding study, between CLA and ELA. ResultsThe mean±SD (95% confidence interval) of the total sample CLA and height were 48.8±13.1 (47.7–49.9) years and 164±10 (163–165) cm. (i) The percentages of healthy subjects with a deltaLungAge>ULN varied from 1% (Newbury) to 64% (Hansen) in men, and from 20% (Yamaguchi) to 51% (Hansen, Morris and Temple) for women. (ii) Mean±SD ELA was significantly underestimated by 17±19years (Hansen), by 12±23years (Morris and Temple) and was significantly overestimated by 4±19years (Newbury). Mean±SD ELA from Yamaguchi et al. [10] was not statistically different from the CLA (1±14years). ConclusionThe published reference equations did not reliably predict CLA data in the Tunisian population. Awaiting the establishment of reliable equation proper to North African population, we recommend the use of the Yamaguchi et al.’s [10] reference equations.

Characterization of Maximal Respiratory Pressures in Healthy Children

Background: Measurements of maximal voluntary inspiratory (P<smlcap>i</smlcap>_max) and expiratory (P<smlcap>e</smlcap>_max) pressures are used in the management of respiratory muscle disease. There is little data on the appropriate reference range, success rates, or repeatability of P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max in children or on methodological factors affecting test outcomes. Objectives: To determine P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max in healthy children and examine which published reference equations are best suited to a contemporary population. Secondary objectives were to assess within-test repeatability and the influence of lung volumes on P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max. Methods: Healthy children were prospectively recruited from the community on a volunteer basis and underwent spirometry, static lung volumes, and P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max testing. Results: Acceptable and repeatable (to within 20%) P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max were obtained in 156 children, with 105 (67%) children performing both P<smlcap>i</smlcap>_max and P<smlcap>e</smlcap>_max measurements to within 10% repeatability. The reference equations of Wilson et al. [Thorax 1984;39:535–538] best matched our healthy Caucasian children. There was an inverse relationship between P<smlcap>i</smlcap>_max and the percent of total lung capacity (TLC) at which the measurement was obtained (beta coefficient –0.96; 95% CI –1.52 to –0.39; p = 0.001), whereas at lung volumes of >80% TLC P<smlcap>e</smlcap>_max was independent of lung volume (p = 0.26). Conclusion: We demonstrated that the Wilson et al. [Thorax 1984;39:535–538] reference ranges are most suited for contemporary Caucasian Australasian children. However, robust multiethnic reference equations for maximal respiratory pressures are required. This study suggests that 10% within-test repeatability criteria are feasible in clinical practice, and that the use of lung volume measurements will improve the quality of maximal respiratory pressure measurements.

P234 The importance of appropriate reference equations for spirometry: lessons learned from the Cystic Fibrosis Gene Therapy “Run-In” study

Introduction and ObjectivesThe “Run-In” study is an on-going longitudinal, observational study of CF patients assessing outcome measures for a future gene therapy trial. Spirometry is performed at each visit and...

Spirometry values in a Greek population: Is there an appropriate reference equation?

Most published reference values for lung function test (LFT) parameters introduce systematic bias. The aim of this study was to compare measured values of FEV(1) and FVC with the corresponding normal predicted values in a Greek population, and to produce reference equations for LFT parameters in this population. In a cross-sectional study conducted in Macedonia, Greece, 1080 adult healthy, non-smokers (432 men, 648 women, aged 18-80 years), underwent spirometry. Measured values of FVC and FEV(1) were compared with predicted values determined using three existing sets of reference equations: one recently derived from a European population and two others widely used in Europe (European Coal and Steel Community; ECSC) and the USA (National Health and Nutrition Examination Survey; NHANES III). Height and age were entered into the multivariate regression analysis to produce reference equations for LFT parameters. All three published sets of equations underpredicted FEV(1) in men. FVC was accurately predicted by all equations except NHANES III. The discrepancy was even greater among women; the ECSC equation underpredicted both FEV(1) and FVC, the NHANES III equation overpredicted both FEV(1) and FVC, while the third set of equations accurately predicted FEV(1) but overpredicted FVC. The derived reference equation for FEV(1) in men was -0.28 × age + 0.057 × height - 4.91, and in women -0.021 × age + 0.039 × height - 2.58. The derived reference equation for FVC in men was -0.28 × age + 0.071 × height - 6.763, and in women -0.019 × age + 0.056 × height - 5.018. Measured FEV(1) and FVC values in a Greek population differed significantly from those predicted using previously published reference equations. The new locally derived spirometry reference equations may be more suitable for evaluation of lung function in everyday practice.

Infection, Inflammation, and Lung Function Decline in Infants with Cystic Fibrosis

Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies. To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation. Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV(0.5)), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing. Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were -0.8 (1.0), -0.9 (1.1), and -1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV(0.5) were -1.4 (1.2), -2.4 (1.1), and -4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P=0.003), and FEV(0.5) z-scores 0.96 lower (P=0.001), respectively. Significantly greater decline in FEV(0.5) z-scores occurred in those infected with Staphylococcus aureus (P=0.018) or Pseudomonas aeruginosa (P=0.021). In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.

Reference values for paediatric pulmonary function testing: The Utrecht dataset

Since populations evolve, measurement protocols and equipment improve and analysis techniques progress, there is an ongoing need to reassess reference data for pulmonary function tests. Furthermore, reference values for total lung capacity and carbon monoxide diffusion capacity are scarcely available in children. We aimed to provide updated reference equations for most commonly used pulmonary function indices in Caucasian children. In the 'Utrecht Pulmonary Function Reference Data Study' we collected data in Caucasian children aged 2-18 years. We analyzed them using the 'Generalized Additive Models for Location Scale and Shape' (GAMLSS) statistical method. Measurements of interrupter resistance (R(int)) (n=877), spirometry (n=1042), body plethysmography (n=723) and carbon monoxide diffusion/helium dilution (n=543) were obtained in healthy children. Height (or the natural logarithm of height) and age (or the natural logarithm of age) were both significantly related to most outcome measures. Also sex was a significant determinant, except for RV, RV/TLC, FRC(pleth), Raw(0,5), Raw(tot), R(int) and FEF values. The application of previously published reference equations on the study population resulted in misinterpretation of pulmonary function. These new paediatric reference equations provide accurate estimates of the range of normality for most commonly used pulmonary function indices, resulting in less underdiagnosis and overdiagnosis of pulmonary diseases.

Potential misinterpretation of infant lung function unless prospective healthy controls are studied

SUMMARY RATIONALE: Reliable interpretation of pulmonary function tests relies on appropriate reference data, which remain very limited for infants. This study aimed to assess the validity of published reference equations for forced expiratory flow-volume (FEFV) data in infants when using current, commercially available equipment, and how this could impact on interpretation of results from infants with lung disease. The Jaeger Masterscreen BabyBody (v4.67) equipment was used to perform partial and raised volume FEFV maneuvers in healthy infants and those with cystic fibrosis (CF). Results were initially expressed as Z-scores using published reference equations. Multilevel modeling was used to calculate differences, if any, from predicted scores in healthy infants. Data were available from 66 healthy full term infants on 89 test occasions; [median (range) postnatal age 49.4 (12-101) weeks. All FEFV outcomes were significantly lower than predicted, with mean (SD) Z-score differences of -0.4 (1.1) for FVC; -0.6 (1.0) for FEV(0.5); -1.0 (1.0) for FEF(25-75) and -1.4 (1.1) for V'(maxFRC). After adjustments using multilevel modeling, mean Z-scores were within 0.1 (SD approximately 1.0) predicted for all outcomes in healthy infants. Among 50 infants with CF, studied on 85 test occasions, results were "abnormal" (<-1.96 Z-scores) on 35 (41%) and 37 (45%) test occasions for FEV(0.5) and FEF(25-75), respectively, when using published equations. This fell to 24 (28%) and 20 (24%), respectively, after adjustment. Dependence on published equations for interpreting FEFV data in infants may lead to misinterpretation of lung function status, which could impact adversely both in the research setting and on clinical management. Use of a contemporary control group or establishment of equipment-specific reference data is essential for meaningful interpretation of infant lung function data.

Reference values for lung function: past, present and future

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 (FEV(1)) or 0.70 FEV(1)/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.