1. PFT STANDARDS AND INTERPRETATION: RECOMMENDATIONS OF RECENT GUIDELINES Ankara University Medical School Department of Pulmonary Diseases Prof Dr Sevgi BARTU SARYAL

2. STANDARDISATION OF SPIROMETRY: WHY? Lung function tests are more useful to the cliinician when performed with appropriate technique with an accurate system. Using standard techniques for the performance of the tests minimize diagnostic and therapeutic errors. Standardisation reduces the noice in lung function measuremnts and improves the identification of the signal of interest. Crapo RO Respir Care 2003;48:764 Crapo RO Respir Care 2003;48:764

3. Effect of smoking on FEV1 Age Ethnical group Socioeconomic factors Occupation Technical Gender Height SOURCES OF NOICE IN SPIROMETRY Signal: The parameter primarily sought by PFT Noice: Other sources of variation that mask the signal Crapo RO Respir Care 2003;48:764

4. SOURCES OF INTERINDIVIDUAL VARIABILITY Technical Ethnic origin Other ( illness, exposure, socioeconomic) Height Gender Age Becklake MR. Am J Med 1986;80:1158

5. GUIDELINES FOR STANDARDISATION OF SPIROMETRY 1979- ATS. Snowbird Workshop on Standardization of spirometry 1983- ECSC. Standardized Lung Function Testing 1987-ATS. Standardization of Spirometry. Update. 1993- ERS (ECSC). Lung Volumes and Forced Ventilatory Flows: Report of Working Party, Standardization of Lung Function Tests 1995- ATS. Standardization of Spirometry 2005-ATS/ERS Task Force: Standardisation of Lung Function Testing

6. ATS/ERS Task Force: Standardisation of Lung Function Testing ERJ 2005 Pellegrino R, Viegi G, Brusasco V, Crapo RO, Casaburi R, Coates A Enright P Van der Grinten C Gustafsson P Jensen R Johnson DC Pedersen OF Wanger J Miller MR MacIntyre N, McKay R Navajas D Hankinson J

7.  GENERAL CONSIDERATIONS Miller MR. General considerations for lung function testing. ERJ 2005;26:153  SPIROMETRY Miller MR. Standardisation of spirometry. ERJ 2005;26:319  LUNG VOLUMES Wanger J. Standardisation of the measurement of lung volumes. ERJ 2005;26:511  DIFFUSING CAPACITY MacIntyre N. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. ERJ 2005;26:720  INTERPRETATION Pellegrino R. Interpretative strategies for lung function tests. ERJ 2005;26:948 ATS/ERS Task Force 2005

8. INDICATIONS FOR SPIROMETRY DIAGNOSTIC  To evaluate symptoms, signs or abnormal laboratory tests bulgularının değerlendirilmesi  To measure the effect of disease on pulmonary function  To screen individuals at risk of having pulmonary disease  To assess prooperative risk  To assess prognosis  To assess health status before strenuous exercise MONITORING  To assess therapeutic intervention  To monitor people exposed to injurious agents  To monitor for adverse reactions to drugs with known pulmonary toxicity DISABILITY / IMPAIRMENT EVALUATIONS  To assess patients as part of a rehabilitation programme  To assess risks as part of an insurance evaluation  To assess individuals for legal reasons PUBLIC HEALTH  Epidemiological surveys  Derivation of reference equations  Clinical research

9. SPIROMETRY STANDARDISATION EQUIPMENT PERFORMANCE CRITERIA EQUIPMENT VALIDATION QUALITY CONROL SUBJECT/PATIENT MANOEUVRES MEASUREMENT PROCEDURES ACCEPTABILITY REPEATABILITY REFERENCE VALUE/INTERPRETATION CLINICAL ASSESSMENT QUALITY ASSESSMENT FEEDBACK TO TECHNICIAN ATS 1994 ATS/ERS 2005

10. PERFORM FVC MANEUVER Meet acceptibility criteria Acceptible maneuvers  3 Meet reprodubility criteria Best test curve: Largest sum FVC+FEV1 Determine other parameters STORE AND INTERPRET Determine largest FVC and FEV1 YES NO ATS 1994 ATS/ERS 2005

11. SPIROMETRY ACCEPTABILITY CRITERIA  No artefacts : Cough or glottis closure during the first second of exhalation, early termination or cutoff, variable effort, leak, obstructed mouthpiece  Have good starts: Extrapolated volume less than 5% of FVC or 0.15 L OR; time to PEF of less than 120 ms  Have a satisfactory exhalation: 6 sn of exhalation and/or a plateau in the volume-time curve OR; reasonable duration of a plateau in the volume- time curve OR; if the subject cannot or should continue to exhale

12. UNACCEPTABLE TESTS Cough Leak Variable effort Early termination Glottis closure

13. SPIROMETRY REPEATABILITY CRITERIA  After 3 acceptable spirograms: The two largest FVC values must be within 0.15 L The two largest FEV 1 must be within 0.15 L TEST SESSION MAY BE COMPLETED  If these criteria are not met, continue test until Both criteria are met with new tests OR; 8 tests are performed OR; The subject cannot or should not continue  Save the three satisfactory manoeuvres

14. INTERPRETATION Review and comment on test quality Comparison of test results with reference values Comparison with known disease or abnormal physiological patterns (obstruction, restriction) Self comparison with former values Answer the clinical question that prompted the test

15. REFERENCE EQUATIONS Predicted values should be obtained from studies of healthy subjects with the same anthropometric (sex, age, height) and ethnic characteristics. Height and weight should be measured at the time of testing If possible, all parameters should be taken from the same reference source

16. REFERENCE EQUATIONS AND ETHNIC DIFFERENCE Race-ethnic reference equations should be used if possible. If such equations are not available, a race/ethnic adjustment factor based on published data may be used for lung volumes. Caucasian formulas tend to overpredict values in Black subjects by  12 % for TLC, FEV1 and FVC,  7 % for FRC and RV. An adjustment factor of 0.94 is also recommended for Asian-Americans. NHANES equations for USA and ECSC equations for Europe are recommended.

17. National Health and Nutrition Examination Survey ( NHANES III). For average sized men, the differences between 3 ethnic groups are not constant with age. Ethnic differences in lung function cannot be controlled by applying a single correction factor to white-based reference values Hankinson JL. AM Rev Respir Dis 1999;159:179

18. LABORATORY NORMALS Formerly (ATS 1991) comparison of selected reference equations with measurements performed by a representative sample of healthy subjects (20-40) tested in each laboratory was recommended. The reference equations that provided the sum of residuals ( observed – predicted ) closest to zero was considered appropriate for that laboratory. However, in the last consensus it has been stated that larger samples (n= 100) are needed, therefore this is impractical.

19. UPPER AND LOWER LIMITS OF NORMAL Publications on reference equations should include explicit definitions of the upper and lower limits of normal range. For every functional parameter, values below the 5th percentile of the frequency distribution of values, measured in the reference equation are considered to be below the expected normal range.

20. Mean and 5th percentile of FEV1 in men of 1.80 m height as a function of age, data form healthy never smoking men aged 18-60 years BRANDLI, O et al. Thorax 2000;55:172 REFERENCE EQUATIONS FOR 5th PERCENTILE MEAN and 5th PERCENTILE in MEN SAPALDIA Study conducted on 1267 men and 1890 women:

21. BRANDLI, O et al. Thorax 2000;55:172 Mean and 5th percentile of FEV1 in women of height 1.65 m as a function of age, data from healthy never smoking women aged 18- 60 years. REFERENCE EQUATIONS FOR 5th PERCENTILE MEAN and 5th PERCENTILE in WOMEN SAPALDIA Study conducted on 1267 men and 1890 women:

22. TYPES OF VENTILATORY DEFECTS Obstructive abnormalities Restrictive abnormalities Mixed abnormalities

23. OBSTRUCTIVE ABNORMALITIES An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to maximal volume (VC) that can be displaced from the lung. Is defined by a reduced FEV1/VC ratio below the 5th percentile of the predicted value.

24. OBSTRUCTION in EARLY and ADVANCED DISEASE EARLY PHASE : A slowing in the terminal portion of the spirogram due to airflow obstruction of small airways occurs. This slowing of expiratory flow is reflected in a concave shape of flow-volume curve. Proportionally greater reduction in FEF75 or FEF25- 75 than FEV1 occurs. ADVANCED PHASE: Central airways are involved with reduction in FEV1 out of proportion to the reduction in VC.

25. OBSTRUCTION and OTHER PARAMETERS Measurement of lung volumes is not mandatory to identify an obstructive defect. An increase in TLC, RV or the RV/TLC ratio above the upper limits of natural variability may suggest the presence of emphysema, asthma or the degree of lung hyperinflation. Airflow resistance is more sensitive for detecting narrowing of extrathoracic or large central intrathoracic airways than peripheral intrathoracic airways. It may be useful in patients unable to perform a maximal forced expiratory manoeuvre.

26. The definition of obstructive ventilatory defect in ATS/ERS task force is consistent with 1991 ATS Statement but contrasts with the definitions suggested by GOLD and ERS/ATS guidelines on COPD in preference of VC rather than FVC and 5th percentile rather than fixed FEV1/FVC ratio of 0.70. FVC has been replaced by VC because FVC is more dependent on flow and volume. FEV1/VC ratio is more capable of accurately identifying more obstructive patients. In contrast with a fixed value (0.70) 5th percentile does not lead to overestimation of ventilatory defect in older people with no history of exposure to noxious particles or gases. FIXED VALUES vs 5th PERCENTILE

27. LOWER LIMIT OF NORMAL A decrease in major spirometric parameters such as FEV1, VC, FEV1/VC and TLC below 5th percentile is useful in clinical practice. When these variables lie near the upper or lower limits of normal; tests including bronchodilator response, DLCO, gas exchange evaluation, respiratory muscle strength or exercise testing are recommended.

28. GOLD2007Postbronkodilator FEV1/FVC FEV1 ERS/ATS2004 NICE 2004 FEV1 FEV1 MildModerateSevere Very severe <% 70  %80 <% 70 %50-80 <% 70 %30-50 <% 70 < 30  0.7  %80  0.7 % 50-80  0.7 % 30-50  0.7 <% 30 % 50-80 % 30-49 < % 30

29. Hansen, J. E. et al. Chest 2007;131:349-355 NHANES III: Underidentification (30-50 years of age) and overidentification (elderly) of airway obstruction, by decade, in 5,906 never-smokers and 3,497 current-smokers using the GOLD of FEV1/FVC< 70% as a criterion The GOLD guidelines misidentify one half of abnormal younger adults as normal and 1/5 of normal adults as abnormal.

30. Area under LLN’ın Normal False negative False positive NHANES III. The ratio of FEV1/FVC in healthy white women falls below 0.70 at about age 52. This would occur in men in their early 40’ s. Hankinson JL. AJRCCM 1999;159:179

31. According to GOLD criteria, FEV1/FVC< 0.70 and FEV1  % 80 means Stage I disease. In ages 47-49 when LLN for FEV1/FVC is % 80 normal subjects may be regarded as having mild COPD. Over age 50, LLN for FEV1 < % 80 may be regarded as having moderate disease although they are normal.

32. Spirometry record of 18.112 adults showed overall 11.7 % discordance between % pred and 5th percentile. More discordence was observed in women and in shorter and older patients. Aggarwal AN. Respir Care 2006;51:737

33. RESTRICTIVE ABNORMALITIES A restrictive ventilatory defect is characterised by a reduction in TLC below 5th percentile of the predicted value and a normal FEV1/VC. Restrictive ventilatory defect should be suspected when VC is reduced, FEV1/VC is increased(>85-90%) and the flow-volume curve shows a convex pattern.

34. A reduced VC and a normal or slightly increased FEV1/VC is often caused by submaximal inspiratory or expiratory efforts and/or patchy peripheral airflow obstruction and a reduced VC itself does not mean a restrictive defect. Pneumothorax and noncommunicating bullae are characterised by a normal FEV1/VC and TLCPL but low FEV1 and VC values. In these conditions, TLC measured by gas dilution techniques will be low. A low TLC from a single-breath test (such as VA from DLCO test) should not be interpreted as restriction since such measurements underestimate TLC. COMMENTS ON LUNG VOLUMES

35. Categorisation of Restrictive Pattern SEVERITY ATS/ERS 2005 ATS1991 MildModerate Moderately severe Severe Very severe FEV1%  70 FEV1% 60-69 FEV1% 50-59 FEV1% 35-49 FEV1% < 35 VC %  70 VC % < 70-  60 VC % < 60-  50 VC % < 50-  35 VC % < 35

36. Venkateshiah SB. Lung 2008;186:19 The aim of the retrospective study was to determine the utility of FVC, FEV1 ve FEV 1/FVC ratio in diagnosing restriction proven by measurement of lung volumes in 2213 restrictive cases.  The negative predictive value for normal FVC was high ( % 95.7)  Combined criterion of FVC< LLN ve FEV1/FVC  LLN was not so sensitive for excluding restrictive defect. THE UTILITY OF SPIROMETRY IN ASSESSMENT OF RESTRICTION

37. MIXED ABNORMALITIES A mixed ventilatory defect is characterised by the coexistence of obstruction and restriction. Is defined as FEV1/VC ratio and TLC below the 5th percentiles of the predicted. Since VC may be equally reduced in obstruction and restriction, the presence of a restrictive component in an obstructed patient cannot be detected from measurements of FEV1 and VC. If FEV1/VC and VC is low, restriction cannot be differentiated from hyperinflation. When FEV1/VC is low but VC is normal a superimposed restriction can be ruled out.

38. Severity scores are closely related with independent indices of performance such as; Ability to work Function in daily life MorbidityPrognosis

39. CLASSIFICATION OF SEVERITY The severity of pulmonary function abnormalities is based on FEV1 % pred. This does not apply to upper airway obstruction. In addition, it might not be suitable for comparing different pulmonary diseases. At very severe stages of diseases FEV1 may fail to identify exact severity. FEV1 % pred correlates poorly with symptoms and may not accurately predict clinical severity or prognosis.

40. Degree of Severity FEV1 % pred MildModerate Moderately severe Severe Very severe 7060-6950-5935-49<35 Severity of any spirometric abnormality based on FEV1 ATS/ERS 2005 has recommended the severity classification of both obstruction and restriction according to FEV1.

41. ADDITIONAL MEASUREMENTS FOR CLASSIFICATION The degree of lung hyperinflation (TLC, FRC, RV, RV/TLC) parallels the severity of airway obstruction. Resting lung hyperinflation (IC/TLC) is an independent predictor of respiratory and all- cause mortality in COPD patients. Casanova C. AJRCCM 2005;171:591 Casanova C. AJRCCM 2005;171:591 Expiratory flow limitation is also related with increased dyspnea and cardiovascular side effects. Tidal and forced expiratory flow- volume curves can be compared. Milic-Emili J. AJRCCM 1996;154:1726 Milic-Emili J. AJRCCM 1996;154:1726

42. Can severity of restriction be classified by FEV1? The data from 361 patients with restrictive pattern were classified according to ATS 1991 and ATS/ERS 2005 classification of severity criteria and the results were compared. 212 (58.7 %) had identical severity categorisation. Of the 149 discordant results, 91 (60.1%) were placed in a better category and 58 (39.9 %) in a worse category using the new ATS/ERS classification. The new guidelines tend to underestimate the severity of restriction in 25 % of patients. It has been suggested that TLC should be measured when FVC is low and FEV1/FVC ratio is normal. Aggarwal AN. Respirology 2007;12:759

43. BRONCHODILATOR RESPONSE Bronchodilator responsiveness to bronchodilators is defined as an integrated physiological response involving airway epithelium, nerves, mediators and bronchial smooth muscle. The response to a bronchodilator can be tested either after a single dose or after a clinical trial conducted over 2-8 weeks. There is no consensus about the drug, dose or mode of administering a bronchodilator in the laboratory.

44. RECOMMENDED BRONCHODILATOR TEST Assess baseline lung function Administer salbutamol in four separate doses of 100  g through spacer Reassess lung function after 15 min. If the effect of different bronchodilator to be assessed, use the same dose and route as used in clinical practice. An increase in FEV1 and/or FVC  12% of control and  200mL constitutes a positive bronchodilator response. The lack of a bronchodilator response in the laboratory does not preclude a clinical response to bronchodilator therapy.

45. INTERPRETATION OF CHANGE IN LUNG FUNCTION Evaluation of an individual’s change in lung function following an intervention or over time may be more valuable than a single comparison with predicted values. For tracking change, FEV1 has the advantage of being most repeatable PFT parameter and one that measures changes in both obstructive and restrictive diseases. Other parameters such as VC, IC, TLC and DLCO may be tracked in ILD or severe COPD patients. When too many indices are tracked simultaneously, the risk of false-positive indications of change increases.

46. Within a day Normal subjects  5 5  5 5  13>7% COPD patients  11  13  23 Week to week Normal subjects  11  12  21 >6 units COPD patients  20  30 >4 units Year to year  15 >10% DL,CO FEF25–75% FEV1FVC ATS 1991 ATS/ERS 2005 CHANGES IN PFT PARAMETERS Year to year changes in FEV1 over 1 year should exceed 15% before being accepted as a clinically meaningful change.

47. CENTRAL AND UPPER AIRWAY OBSTRUCTION  Occurs in extrathoracic ( pharynx, larynx, extrathoracic portion of the trachea) and intrathoracic (intrathoracic trachea and main bronchi ) airways.  Does not lead to reduction in FEV1 and/or VC, but PEF can be severely affected.  Increased FEV1/PEF (mL.L -1.min -1 ) ratio must alert the clinician to the need for an inspiratory and expiratory flow- volume loop. FEV1/PEF> 8 suggests central or upper airway obstruction.  Poor initial effort can also affect this ratio.  At least three maximal and repeatable flow-volume curves are necessary. ERS/ATS 2005 CENTRAL AIRWAY OBSTRUCTION FEF50/FIF50 > 1, FEV1/FEV0.5  1.5 ERS 2003

48. Variable intrathoracic upper airway obstruction Variable extrathoracic upper airway obstruction Fixed upper airway obstruction EXTRATHORACIC OBSTRCTION VARIABLE FIXED INTRATHORACIC OBSTRUCTION PEF Decreased Normal or decreased Decreased FIF50 Normal or decreased Decreased Decreased FIF50/FEF50 > 1 < 1  1 ERS/ATS 2005