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ERS Annual Congress Amsterdam

26–30 September 2015

EDUCATIONAL MATERIAL

Meet the expert 10

Paediatric lung function tests reference values

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3

Paediatric Lung Function Tests: Reference Values

Dr Sanja Stanojevic Division of Respiratory Medicine

Hospital for Sick Children 555 University Avenue

M5G 1X8 Toronto CANADA

sanja.stanojevic@sickkids.ca

AIMS: To review the key points regarding the use of appropriate reference values for lung function testing in children and their correct interpretation. The session will focus on both spirometry and the reference values for lung function techniques in preschool children. TARGET AUDIENCE: Caretakers who use lung function testing to manage paediatric patients, paediatric pulmonologists, paediatric nurses, and paediatric lung function technicians.

AIMS

Describe why reference equations are important and relevant to daily practice Describe the Global Lung Function Initiative and its advantages Discuss interpretation of lung function results in different ethnic groups Discuss different approaches to interpreting lung function test results Review several examples of paediatric lung function tests and how to interpret results

SUMMARY

Lung function results can help with establishing a diagnosis, with assessment of treatment effects and with making a prognosis. However, arbitrary differences in the way lung function is expressed and interpreted may result in mismanagement of patients as well as hindering our understanding of the global burden of lung disease. In this session I will summarise the Global Lung Function Initiative spirometry reference equations and dispel some common myths related to the use and interpretation of spirometry results. REFERENCES 1. Kirkby J, Aurora P, Spencer H, Rees S, Sonnappa S, and Stocks J, Stitching and switching: the impact

of discontinuous lung function reference equations. Eur Respir J, 2012. 39(5): p. 1256-7. 2. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS,

Zheng J, Stocks J, ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J 2012: 40(6): 1324-1343.

3. Stanojevic, S., Qunajer, P., Miller, M.R., Stocks, J. The Global Lung Function Initiative: dispelling some myths of lung function test interpretation. Breathe: 2013: 9(6): 462-474

4. Quanjer PH, Pretto JJ, Brazzale DJ, Boros PW. Grading the severity of airways obstruction: new wine in new bottles. European Respiratory Journal 2014. 43(2):505-12

44

5. Quanjer PH, Weiner DJ. Interpretative consequences of adopting the global lungs 2012 reference equations for spirometry for children and adolescents. Pediatr Pulmonol 2014: 49(2):118-25:

EVALUATION

1. If the pulmonary function test is done according to the ATS/ERS guidelines, does it not matter what reference equation is use.

a. No, it is only necessary to evaluate the absolute lung function results b. No, every reference equation produces the same percent predicted results c. Yes, reference equations should be representative of the study population, based on a large

representative sample of the study population and developed using appropriate methods to consider how the lungs grow and develop

d. Yes, you should always use reference equations derived at your centre, as long as there are more than 20 patients included in the sample

2. Before performing a lung function test, a patients height should be:

a. Measured at each visit b. Measured once at the first visit c. Measured in children, but adults can self-report their height d. Self-reported in children, but measured in adults

3. When can you start using the Global Lung Function Initiative Reference Equations a. As soon as I buy new equipment for my laborartory b. As soon as the GLI equations are available for all lung function tests (i.e. TLCO, lung volumes). c. As soon as I confirm the equations are in my equipment d. As soon as GLI equations are available for the ethnic group represented in my country

4. In addition to the appropriate reference equations, interpretation of a lung function test results should include (select all that apply):

a. A good effort, that meets current ATS/ERS standards b. An assessment of the patients clinical symptoms and other clinical findings c. Whether the lung function results is within the normal range d. The change in lung function from the previous visit

55

Paediatric Lung Function Tests: Reference Values

Sanja Stanojevic PhD

Division of Respiratory MedicineHospital for Sick Children

Toronto, Canada66

Disclosures

• I have no conflicts to disclose

77

Reference Equations and Zzzzzzzz-Scores

88

Aims

• Describe why reference equations are important and relevant to daily practice

• Describe the Global Lung Function Initiative and its advantages

• Discuss interpretation of lung function results in different ethnic groups

• Discuss different approaches to interpreting lung function test results

• Review several examples of paediatric lung function tests and how to interpret results

99

How big should my lungs be?

Ethnicity

Age

Photos courtesy of www.london2012.com 1010

1111

Choice of 34 equations for spirometry in same commercial equipment!

1212

Switched and stitched into 14 different modules to cover various age ranges and

all possible outcomes

1313

Switched and stitched into 14 different modules to cover various age ranges and

all possible outcomes

1414

Why is this important?

1515

Lack of Universal Reference Equations and Limits of Normal hinders our

understanding of the global burden of lung disease

1616

Tracking of Individual Results

Kirkby et al ERJ 2012

% Predicted

1717

Kirkby et al ERJ 2012

Absolute Values

Tracking of Individual Results

1818

Spirometry from Cradle to the Grave

International GuidelinesLum et al AJRCCM 2005Beydon et al AJRCCM 2007Pellegrino et al. AJRCCM 2005 1919

Ideally Reference Ranges should span All-Ages

2020

The GLI-2012 equations based on collated results from ~74,000 healthy non-smokers aged 3-95 years to create the 1st multi-ethnic all-age lung growth charts

www.lungfunction.org

The Global Lung Function Initiative

2121

GLI Objectives

• Derive internationally valid ‘all-age’ spirometry reference equations

• Specific focus on defining normal ranges

– During early life

– Transition through adolescence

– Shift from growth to plateau

– Age related decline

• Accurate representation of ethnic differences

2222

Eur Resp J 2012; 40, 1324-1343 2323

GLI are endorsed by:

2424

GLI 2012

2525

Ethnic differences in lung function

4.1 Litres 5.9 Litres 6.8 Litres

2626

Ethnicity and spirometry

• Ethnic differences in FEV1 and FVC (shown as % reductions) when compared to white subjects

Quanjer et al ERJ 20122727

FEV1/FVC vs Age

2828

What about the LLN?

2929

What is the LLN?

3030

The ATS/ERS Recommends the 5th Centile

5th Centile-1.64 SDS/z-score

5% of healthy subjects will have values below the 5th centile

The 5% is also called the Lower Limit of Normal (LLN)

3131

Why do we use 80% predicted as a cut-off?

80%

This assumes 1 SD of the between-subject variability is 10%

120%

3232

Between-subject variability varies with age and sex.

CV = 15% ~ LLN of 70%Normal = 70-130%

CV = 10% ~ LLN of 80%Normal = 80-120%

3333

Does it make a difference?

Only 5% of observations should be <LLN in population of healthy subjects.

If use <80% FEV1 as cut off, clear age-related bias.

3434

65

70

75

80

85

0 20 40 60 80 100

FEV

1%

Pre

dic

ted

Age (yr)

Males

3535

Reference Equations and Zzzzzzzz-Scores

3636

3737

What do Z-scores translate to?

3838

Relationship Between Z-scores and % Predicted

3939

Does it make a difference?

4040

Kirkby et al ERJ 2012

Percent Predicted

4141

Kirkby et al ERJ 2012

Absolute Values

4242

GLI Equations Track Continuity

Add 3rd graph

Percent Predicted

4343

Advantages to GLI

In contrast to other commonly used equations, GLI-2012 equations allow appropriate interpretation:

– In very young children– During adolescence– During the transition from paediatric to adult care– In different ethnic groups

GLI-2012 also provides accurate LLN rather than fixed cut-offs for detecting abnormality – relevant throughout the life course

4444

How to use the GLI?

4545

Practical Recommendations

• Express results in relation to lower limit of normal not fixed thresholds

• Measure age and height to ≥ 1 decimal point accuracy to maximise accuracy of predicted values.

• Calibrate stadiometer at least annually and whenever suspect

• Do not use self reported height!

4646

• Altruistic international collaboration to improve diagnosis and management of lung disease

• First reference equations to cover different ethnicities over the entire life span

• International endorsement will streamline interpretation of lung function results

• Provides patients with a far more consistent record of their own lung health

Benefits of the GLI

4747

What about other PFTs?

4848

Acknowledgements

• Those who submitted spirometry data to the GLI

• ATS, TSANZ, ACCP, ANZSRS, APSR

4949

Discussion Slides

5050

Practicalities of Switching Equations

• Educate physiologists & clinicians– Reports must show which reference equation used

– Information sheets

• Educate patients and families– Liaise with Nurses and clinicians, patient representatives

– Information sheets on the website & in clinics

• Trend graphs– Display serial results using same equations

• Improve report format to show normal range

• for5151

Education Leaflets

5252

Practical Examples

5353

5454

5555

5656

5757

5858

5959

6060

6161

6262

Faculty disclosures There are no faculty disclosures for this session.

6363

Answers to evaluation questions

Please find all correct answers in bold below

Paediatric Lung Function Tests: Reference Values - Dr Sanja Stanojevic

1. If the pulmonary function test is done according to the ATS/ERS guidelines, does it not matter

what reference equation is use.

a. No, it is only necessary to evaluate the absolute lung function results

b. No, every reference equation produces the same percent predicted results

c. Yes, reference equations should be representative of the study population, based on a

large representative sample of the study population and developed using appropriate

methods to consider how the lungs grow and develop

d. Yes, you should always use reference equations derived at your centre, as long as there are

more than 20 patients included in the sample

2. Before performing a lung function test, a patients height should be:

a. Measured at each visit

b. Measured once at the first visit

c. Measured in children, but adults can self-report their height

d. Self-reported in children, but measured in adults

3. When can you start using the Global Lung Function Initiative Reference Equations

a. As soon as I buy new equipment for my laborartory

b. As soon as the GLI equations are available for all lung function tests (i.e. TLCO, lung

volumes).

c. As soon as I confirm the equations are in my equipment

d. As soon as GLI equations are available for the ethnic group represented in my country

4. In addition to the appropriate reference equations, interpretation of a lung function test results

should include (select all that apply):

a. A good effort, that meets current ATS/ERS standards

b. An assessment of the patients clinical symptoms and other clinical findings

c. Whether the lung function results is within the normal range

d. The change in lung function from the previous visit