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Interpretation of Pulmonary Function Tests (PFTs) Course # 1612 2:00 5:00pm Friday February 22, 2013 Lung Pathophysiology & PFTs Mark F. Sands MD, FCCP, FAAAAI Division of Allergy, Immunology & Rheumatology AAAAI 2013 Annual Meeting

Faculty for Course #1612 Donald W. Cockroft, MD, FAAAAI Professor in Respiratory Medicine, University of Saskatchewan Meredith C. McCormack, MD, MHS Asst. Professor of Medicine, Johns Hopkins School of Medicine Riccardo Polosa, MD, PhD, FAAAAI Professor of Medicine Departimento di Medicinea Interna e Specialistica, U. of Catania Mark F. Sands, MD, FAAAAI Assoc. Professor of Medicine, SUNY Buffalo School of Medicine Donald P. Tashkin, MD Professor of Medicine, David Geffen School of Medicine, UCLA John M. Weiler, MD, FAAAAI Professor Emeritus Department of Internal Medicine University of Iowa

Conflicts of Interest I have no known conflicts of interest. Disclosures: I have nothing to disclose.

Outline Lung Volumes & Capacities Tests defined Spirometry Indications Readouts Complete PFT Gas dilution Plethysmography DL,CO Flow/Volume Loops Lung pathophysiology Obstructive mechanics Restrictive mechanics References

Lung Volumes and Capacities Maximal inspiratory level Resting expiratory level Maximal expiratory level VC IRV V T IC TLC ERV FRC RV ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; V T, tidal volume; VC, vital capacity. Adapted from Gold. Pulmonary function testing. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. 3rd ed. Philadelphia, Pa: Saunders; 2000:783.

Maximal inspiratory level IRV IC Lung Volumes Resting expiratory level Maximal expiratory level VC V T ERV FRC RV TLC ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; V T, tidal volume; VC, vital capacity. Tidal volume (TV) - Amount of air inhaled or exhaled with each breath during quiet breathing* (~0.5 L) Inspiratory reserve volumes (IRV) Adapted from Gold. Pulmonary function testing. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. 3rd ed. Philadelphia, Pa: Saunders; 2000:783. - additional volume inhaled after quiet inspiration (~2L) Expiratory reserve volumes (ERV) -additional volume exhaled after quiet expiration ~1.2L) Residual Volume (RV)- Amount of air remaining in lungs after maximal expiration (~2L) *or as specified (eg. exercise)

Maximal inspiratory level Lung Capacities Resting expiratory level Maximal expiratory level VC IRV IC V T TLC ERV FRC RV TLC- volume of gas in lungs after maximal capacity. inspiration (RV + ERV + TV + IRV) = (FRC + IC) ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IR inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; V T, tidal volume; VC Adapted from Gold. Pulmonary function testing. In: Murray JF, Nadel JA, eds. Textbook of Respirat Medicine. 3rd ed. Philadelphia, Pa: Saunders; 2000:783. FRC- lung volume present at end-expiration during tidal breathing (RV + ERV) VC- volume change at mouth between full inspiration and full expiration. ERV +TV +IRV) Slow inspiratory - IVC Slow expiratory - EVC Forced vital capacity -FVC

Maximal inspiratory level Lung Capacities Resting expiratory level Maximal expiratory level VC IRV IC V T TLC ERV FRC RV ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IR inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; V T, tidal volume; VC capacity. FVC- amount forcibly exhaled from full inspiration (TLC) to full exhalation (RV). IC- (TV + IRV) Adapted from Gold. Pulmonary function testing. In: Murray JF, Nadel JA, eds. Textbook of Respirat Medicine. 3rd ed. Philadelphia, Pa: Saunders; 2000:783. American Thoracic Society and National Heart, Lung, and Blood Institute Consensus Document 12 Nov 03. Eur Resp J. 2005; 26.

Definition of tests FEV 1 : forced exhaled volume in first second. FEF 25-75 : Average flow rate over mid 50% of FVC (from 25% to 75%) PEF or PEFR: Peak expiratory flow rate The maximum flow rate generated with a forceful expiration (recorded as L/sec or L/min) from TLC FEV 1 /FVC ratio: (FEV 1 %) indicator of obstruction if less than 70%. If high, may reflect restrictive disease.

Definitions of tests FEV 1 (% predicted): (don t confuse with FEV1%) (patient FEV 1 / "normal" FEV 1 ) x 100 the FEV 1 of the subject as a % of predicted for the reference group; normal is > 80%. MVV: The maximum volume of air a subject can breathe over a specified period of time (12 s for normal subjects) expressed in L min-1 at BTPS

Lung Volumes & Capacities Modified from Middleton s Allergy Principles & Practice 6 th Ed. 2003

Spirometry Defined A physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. Output is numeric and graphic Volume-time tracing and/or Flow-volume loop

Indications for Spirometry Diagnostic Evaluate Sx, signs, abnormal lab tests Effect of disease on PFT Screen those at risk for pulmonary disease Pre-operative risk ( or pre-exercise risk) Prognosis Monitoring Response to therapy Disease progression Adverse exposure/drug effect Disability/Impairment Public Health Eur Respir J 2005; 26: 319 338

Spirometry: Measured Forced Vital Capacity (FVC) Forced Expiratory Volume in One Second (FEV 1 ) FEV1 to FVC ratio (FEV 1 /FVC, %) Peak Expiratory Flow Rate (PEF) MMEF (FEF 25-75 ) MVV (Max Voluntary Ventilation) Other VC (Slow) IC (Slow) ERV IRV Not Measured RV FRC TLC DL,CO Compliance Resistance

Normal Spirometry Flow-Volume Loop Volume-Time Plot Observed LLN FVC 6.00 3.88 FEV 1 4.80 3.12 FEV 1 /FVC 80% 71% Courtesy D. Tashkin

Spirometry Exhaled volume (L) 4 3 2 1 FEV1 FEV1 Before bronchodilator After bronchodilator FVC 1 2 3 4 5 6 Time (seconds) Asthma

MMEF (FEF 25-75 )

Measures the FRC Allows determination of the RV Allows determination of TLC Diffusing capacity CO uptake test (not a capacity) Measurement of FRC methods: Gas dilution (Helium) Nitrogen washout Plethysmography SG aw Complete PFT TLC FRC Lung volume alterations in obstructive and restrictive patterns. FR of VC, TLC increases. In restrictive disease TLC, FR RV Obstruction TLC ERV FRC FRC RV Normal ERV TLC

Determining the Elusive TLC Must assess the RV by other than exhalation maneuver. Gas Dilution methods Helium Dilution (He inspired, equilibrates with lung) * Nitrogen Washout (O 2 inspired washes out lung N 2 ) Plethysmography (compressible gas vol.) Has advantage of not underestimating lung volume due to uneven ventilation and incomplete gas mixing or trapped gas in non-communicating or poorly communicating air spaces (e.g., bullae). *note: inspired gas may diffuse into volume less than true lung vol. so final gas concentration too high, making volume look too low.

Helium Dilution Helium Concentration Starting = Final Volume of System Helium Concentration Final Initial Volume of System FRC uncorrected = (C 1 -C 2 ) (Vds + Vadded) Vmp C 2 Fig. Courtesy D. Tashkin

Nitrogen Washout Again, by measuring N 2 concentration and volume of expired gas, and knowing the original concentration of N in the lung, solve for lung gas volume. Courtesy D. Tashkin

Plethysmograph Pressure Box Cotes JE. Lung Function. 6 th Ed.

Plethysmography Concepts TGV (VTG) = plethysmograph measure of intrathoracic gas at time airflow occluded. FRCpleth = lung gas volume with occlusion at FRC Other volumes (e.g., IC and ERV) by breathing maneuvers following measurement of FRC. Boyle s law is underpinning

Plethysmography 101 Boyle s Law (simplified): When a constant mass of gas is compressed (or expands), gas volume decreases (or increases) and gas pressure changes such that the product of vol. and pressure at any moment is constant. P1 x V1 = P2 x V2

Slope of Scope Readout Allows Vpleth Calculation Tanθ VTG= ΔP/ ΔPbox X P B VTG= ΔV/ ΔP X P B Cotes JE. Lung Function. 6 th Ed.

DL,CO: Diffusing capacity Also known as the confusing capacity, Neither a capacity nor a direct measurement of oxygen diffusion. A carbon monoxide transfer test. Measures CO uptake by Hgb in the lung. Any blood in the lung, intra- or extravascular, can take up CO.

Diffusing Capacity DL,CO Breathing minute amounts of CO Transfer/absorption of CO depends upon Ventilation presenting CO to alveolus CO transfer from alveolus through wall Movement across interstitium Uptake by Hgb in RBC in capillary [Hgb] important (correction factor) Correction factors include: Alveolar Volume (VA) DLCO/VA = KCO (controversial) Hemoglobin concentration

DL,CO: Maneuver Single breath of gas with low conc. of carbon monoxide, and an inert gas (He or CH 4 ). Start at RV and inhaled to TLC. 10 sec. breath hold at TLS followed by full exhalation exhaled alveolar gas sampled for [CO] and [He] or [CH 4 ). drop in CO indicates how much diffusion has occurred, He (or CH 4 ) allows for the callculation of volume. Normally 20-30 ml of CO/min/mm Hg occurs.

Flow, L/sec 8 The Flow Volume Loop The Good, The Bad, and...the Unusual 6 Normal 4 Restrictive 2 Obstructive 8 6 4 2 0 Volume, L

Flow/Volume Loops: Obstructive Pattern The Bad Normal exhalation Nl. variant inhalation Asthma- mod. obstruction COPD severe obstruction

Flow/Volume Loops A B B C Normal Restrictive Mixed: Restrictive - Obstructive Eur Respir J 2005; 26

And The Unusual Eur Respir J 2005; 26: 948-68

Obstructive Asthma COPD Restrictive Parenchymal Neuromuscular Musculoskeletal Extra-pulmonary Mixed Pathophysiology

Mechanisms of Airway Obstruction Filling of Lumen Wall Thickening Loss of Tethering

Airway Resistance R = 8lŋ / πr 4 Airway resistance (R) varies (inversely) with the 4 th power of the radius of the airway. This is in laminar flow (Poiseuille s Law) Most flow in smaller airways is laminar l (length tube); ŋ (viscosity); r (radius)

Obstructive Lung Disease Defined An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume (i.e. VC) that can be displaced from the lung It implies airway narrowing during exhalation and is defined by a reduced FEV1/VC ratio below the 5th percentile of the predicted value.

Restrictive Lung Diseases Characterized by reduction in TLC below the 5th percentile of predicted, and a normal FEV1/VC. Lung volumes are reduced Alteration in lung parenchyma Diseases of the pleura, chest wall or neuromuscular apparatus Reduced compliance (pulmonary or extrapulmonary)

Restrictive Pattern in IPF Schwartz & King Interstitial Lung Disease 3 rd Ed. 1998

Course 1608 Part II PFTs & Quality Control Mark F. Sands MD

Acceptable criteria for single maneuvers 1. Satisfactory start (EV <5% or 0.15 L whichever is greater) 2. No cough during 1 st sec 3. No early termination 4. No Valsalva (e.g. glottic closure) 5. No leak 6. No obstructed mouthpiece 7. No extra breath (Usable curve meets 1 and 2 whereas acceptable curve meets all 7)

Normal Spirometry Observed LLN FVC 6.00 3.88 FEV 1 4.80 3.12 FEV 1 /FVC 80% 71%

Hesitation

Early Termination Observed LLN FVC 2.95 3.88 FEV 1 2.76 3.12 FEV 1 /FVC 94% 71%

Submaximal Effort Observed LLN FVC 4.45 3.88 FEV 1 3.00 3.12 FEV 1 /FVC 67% 71%

Cough Observed LLN FVC 5.00 3.88 FEV 1 3.47 3.12 FEV 1 /FVC 69% 71%

Acceptable & Reproducible Efforts

Non-Reproducible Peak Flows Two efforts had submaximal peak flows

Non-Reproducible End-of- Test

Non-Reproducible Exhaled Volumes Maneuvers individually acceptable but exhaled volumes not reproducible: failure to take as deep a breath as possible before 2 of the maneuvers

Selected References 1. N. MacIntyre, R.O. Crapo, G. Viegi. General considerations for lung function testing. ATS/ERS Task Force: Standardisation of lung function testing. Eur Respir J 2005; 26:13-161. 2. N. MacIntyre, R.O. Crapo, G. Viegi. Standardization of spirometry ATS/ERS Task Force: Standardisation of lung function testing. Eur Respir J 2005; 26:319-338. 3. N. MacIntyre, R.O. Crapo, G. Viegi. Standardisation of the measurement of lung volumes. Eur Respir J 2005; 26:511-522. 4. N. MacIntyre, R.O. Crapo, G. Viegi. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26:720-735. 5. N. MacIntyre, R.O. Crapo, G. Viegi. Interpretative strategies for lung function tests. Eur Respir J 2005; 26:948-968. 6. Murray JF, Nadel JA. Textbook of Respiratory Medicine 2 nd Ed. WB Saunders CO. Philadelphia, 1994. 7. Cotes JE, Chinn DJ, Miller MR. Lung Function. 6 th Ed. Blackwell Publishing 2006. 8. Dakin J, Kourteli E, Winter R. Making Sense of Pulmonary Function Tests. A hands-on guide. Arnold (Oxford University Press) N.Y. 2003.

Thank You! 67 Sands 2010