Pulmonary Function Testing: Concepts and Clinical Applications. Potential Conflict Of Interest. Objectives. Rationale: Why Test?

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Pulmonary Function Testing: Concepts and Clinical Applications David M Systrom, MD Potential Conflict Of Interest Nothing to disclose pertinent to this presentation BRIGHAM AND WOMEN S HOSPITAL Harvard Medical School Objectives Understand common indications for testing Review components of PFTs Recognize patterns of PFT abnormalities in disease Gain familiarity with interpretation strategies Rationale: Why Test? Evaluate symptoms/signs of respiratory disease Monitor course of disease and response to therapy Prognosticate Screen patients at risk pre-operative systemic disease or systemic therapy with known pulmonary effects occupational exposure Evaluate disability Components of Pulmonary Function Testing Routine Exhaled volume and flow rates -spirometry Lung volumes-helium dilution or plethysmography Diffusion characteristics -diffusion capacity Airway reactivity-bronchodilator response or methacholine challenge Oxygenation/Ventilation-pulse oximetry or arterial blood gas analysis Components of Pulmonary Function Testing Specialized Respiratory muscle strength-maximal inspiratory and expiratory pressures (MIPs and MEPs) Heart-lung interaction-integrated integrated cardiopulmonary exercise testing Novel assays of exhaled gas

Spirometry Most basic and widely used formal pulmonary function test Easily performed in the office setting Part of the initial evaluation of patients with undiagnosed chest complaints Sensitive and specific test for the presence of airflow obstruction as may occur in asthma, COPD, bronchiectasis Less specific test for restrictive lung disease FVC 1.56 66 FEV 1 0.66 36 FEV 1 /FVC 0.42 56 PEFR 1.56 31 0.26 16 63 y/o Man with Dyspnea A. Obstruction due to the reduced B. Restriction due to the reduced FVC C. Obstruction due to the reduced FEV 1 /FVC D. Inadequate effort on the basis of marked expiratory coving of the flow-volume loop FVC 1.56 66 FEV 1 0.66 36 FEV 1 /FVC 0.42 56 PEFR 1.56 31 0.26 16 63 y/o Man with Dyspnea Spirometry Spirometry measures inhaled and exhaled gas volumes and gas flows during a forced vital capacity maneuver A. Obstruction due to the reduced B. Restriction due to the reduced FVC C. Obstruction due to the reduced FEV 1 /FVC D. Inadequate effort on the basis of marked expiratory coving of the flow-volume loop Definitions and Terms FEV 1 -forced expiratory volume in the first second FVC -forced vital capacity FEV 1 /FVC-ratio of the FEV 1 to FVC (as a %) - average forced expiratory flow during the mid portion of the FVC PEFR-peak expiratory flow rate Definition of Normal Values Predicted values are standardized to age, sex, height, and race; measured values are expressed as a percentage of predicted Current ATS guidelines suggest that values below the 95% CI be considered abnormal This recommendation has not been universally adopted

22 y/o Woman with Wheezing and Chest Tightness FVC 2.28 75 FEV 1 1.40 57 FEV 1 /FVC 0.62 78 PEFR 3.23 56 FEF 75-25 0.74 29 A. Obstruction due to the reduced PEFR B. Restriction due to the reduced FVC and FEV 1 C. Obstruction on the basis of marked expiratory coving of the flow-volume loop D. Obstruction due to the reduced FEV 1 /FVC 22 y/o Woman with Wheezing and Chest Tightness FVC 2.28 75 FEV 1 1.40 57 FEV 1 /FVC 0.62 78 PEFR 3.23 56 FEF 75-25 0.74 29 A. Obstruction due to the reduced PEFR B. Restriction due to the reduced FVC and FEV 1 C. Obstruction on the basis of marked expiratory coving of the flow-volume loop D. Obstruction due to the reduced FEV 1 /FVC Spirometry- Obstructive pattern Limitation to expiratory flow characterized by reduced FEV 1, relatively preserved FVC, reduced FEV 1 /FVC Emphysema loss of elastic recoil Chronic bronchitis mucus hypersecretion mucosal thickening bronchospasm Asthma smooth muscle contraction airway edema Bronchiolitis mucosal inflammation 22 y/o Woman with Wheezing and Chest Tightness FVC 2.28 75 FEV 1 1.40 57 FEV 1 /FVC 0.62 78 PEFR 3.23 56 0.74 29 What should be ordered next? A. diffusion capacity B. post-bronchodilator spirometry C. methacholine challenge D. ambulatory peak flow monitoring E. allergen skin testing 22 y/o Woman with Wheezing and Chest Tightness FVC 2.28 75 FEV 1 1.40 57 FEV 1 /FVC 0.62 78 PEFR 3.23 56 0.74 29 What should be ordered next? A. diffusion capacity B. post-bronchodilator spirometry C. methacholine challenge D. ambulatory peak flow monitoring E. allergen skin testing Bronchodilator Testing Assessment of lung function (spirometry) pre- and 15 minutes post- administration of a bronchodilator document reversible airflow obstruction asthma diagnosis prognosticate in COPD may imply an increased likelihood of response to CS immediate feedback to patients may increase compliance lack of an acute response does not imply lack of response to long-term therapy

22 y/o Woman-Bronchodilator Response % pred post %change FVC 2.28 75 2.45 7 FEV 1 1.40 57 1.63 16 FEV 1 /FVC 0.62 78 0.66 6 PEFR 3.23 56 5.03 55 0.74 29 0.94 27 Positive response: 12% increase in FEV 1 or FVC, and an increase of 200 cc Bronchodilator Testing When to test suspected new diagnosis of obstructive lung disease asthma, COPD, emphysema, bronchiolitis, bronchiectasis f/u to assess efficacy of treatment corticosteroids and long-acting bronchodilators (salmeterol) may alter bronchodilator response 38 y/o Man with Episodic Cough 38 y/o Man with Episodic Cough Close friend recently hospitalized with asthma Spirometry: FVC 4.99 98 FEV 1 4.09 97 FEV 1 /FVC 0.82 100 PEFR 8.45 90 3.45 78 What should be ordered next to r/o asthma? A. diffusion capacity B. post-bronchodilator spirometry C. methacholine challenge D. ambulatory peak flow monitoring E. allergen skin testing Close friend recently hospitalized with asthma Spirometry: FVC 4.99 98 FEV 1 4.09 97 FEV 1 /FVC 0.82 100 PEFR 8.45 90 3.45 78 What should be ordered next to r/o asthma? A. diffusion capacity B. post-bronchodilator spirometry C. methacholine challenge D. ambulatory peak flow monitoring E. allergen skin testing Bronchial Challenge Testing Bronchial challenge testing detects airway hyper- reactivity as may occur in asthma, COPD, and bronchiectasis Methacholine is administered by nebulizer in increasing concentrations spirometry is measured at baseline and after each concentration. the degree of airflow obstruction present after any given concentration is a reflection of airway reactivity patients with hyper-reactive reactive airways will bronchoconstrict at lower concentrations FEV 1 (% baseline) Bronchial Challenge Testing Hyper-reactive 100 80 60 40 20 PC 20 = 6.2 mg/ml 0 0 1 2 3 4 5 6 7 8 9 10 McH (mg/ml) FEV 1 (% baseline) 100 80 60 40 20 Non-reactive PC 20 =? 0 0 1 2 3 4 5 6 7 8 9 10 McH (mg/ml)

Bronchial Challenge Testing The concentration required to induce a 20 % fall in FEV 1 (PC 20 ) is reported. < 8 mg/ml is hyper- reactive Airway hyper-reactivity reactivity may be present in ~15% of normal A negative methacholine challenge excludes asthma in the absence of concurrent therapy with: corticosteroids (6 wks) leukotriene modifiers (48 hours) long-acting bronchodilators (48 hours) theophyline (1 week) cromolyn (1 week) Bronchial Challenge Testing Indications suspicion of asthma with normal spirometry and a negative bronchodilator response chronic cough nocturnal cough episodic chest tightness unexplained exercise intolerance recurrent bronchitis 30 y/o Man with Dyspnea and Cough Spirometry: FVC 1.12 19 FEV 1 1.04 21 FEV 1 /FVC 0.93 115 PEFR 5.75 72 2.2 48 A. Suggested obstruction due to the reduced PEFR B. Restriction due to the increased FEV 1 /FVC C. Obstruction on the basis of the reduced FEV 1 D. Suggested restriction due to the reduced FEV 1 and FVC 30 y/o Man with Dyspnea and Cough Spirometry: FVC 1.12 19 FEV 1 1.04 21 FEV 1 /FVC 0.93 115 PEFR 5.75 72 2.2 48 A. Suggested obstruction due to the reduced PEFR B. Restriction due to the increased FEV 1 /FVC C. Obstruction on the basis of the reduced FEV 1 D. Suggested restriction due to the reduced FEV 1 and FVC Spirometry: Restrictive pattern Reduction in gas volume of the chest characterized by symmetric reduction in FEV 1 and FVC; FEV 1 /FVC is preserved reduced chest wall compliance loss of parenchyma (i.e. s/p resection) increased parenchymal stiffness respiratory muscle weakness Spirometry can measure only exhaled gas, not the total gas in the chest; it can only suggest a diagnosis of restriction Absolute Lung Volumes After complete exhalation, residual air remains in the lung (RV) Without quantification of the RV, the total volume of gas in the chest (TLC) cannot be determined Direct measurement of lung volumes is necessary for the formal diagnosis of restriction

Measurement of the residual volume (RV) Significance of the TLC and RV Helium dilution Plethysmography A reduction in TLC defines restriction which may have only been suggested by a reduced FVC A normal TLC excludes restriction which may have been suggested by a reduced FVC measured by spirometry An elevated RV indicates gas trapping as can be seen in severe obstructive lung disease 30 y/o Man with Dyspnea and Cough Spirometry: FVC 1.12 19 FEV 1 1.04 21 FEV 1 /FVC 0.81 115 PEFR 5.75 72 2.2 48 TLC 2.09 28 Suggested restriction due to the reduced FEV 1 and FVC Confirmed restriction due to the reduced TLC Diffusing Capacity (D L ) quantifies the transfer of oxygen from alveolar gas to the red cell The quantity and rate of oxygen transfer depends on area (A)( ) of the alveolar- capillary membrane thickness (T)( driving pressure (ΔPo( 2 ) A ΔPo 2 DL = T Abnormalities in DLD CO Increased DLD CO supine position polycythemia alveolar hemorrhage left-to to-right shunt early CHF asthma Decreased DLD CO decreased area emphysema, s/p resection, pulmonary emboli/htn anemia increased thickness pulmonary fibrosis, pneumonconiosis,, sarcoid, drug-induced lung disease, CHF increased CO back- pressure cigarette smoking Abnormalities in TLC/DL CO FVC 1.12 (19%) FEV 1 1.04 (21%) FEV 1 /FVC.93 (100%) TLC 2.10 (28%) DL CO /V A 15 (43%) A. Emphysema B. Interstitial lung disease C. Diaphragmatic dysfunction D. Primary pulmonary hypertension

Abnormalities in TLC/DL CO FVC 1.12 (19%) FEV 1 1.04 (21%) FEV 1 /FVC.93 (100%) TLC 2.10 (28%) DL CO /V A 15 (43%) A. Emphysema B. Interstitial lung disease C. Diaphragmatic dysfunction D. Primary pulmonary hypertension Abnormalities in TLC/DL CO 37 y/o woman TLC 3.35 (71%) FVC 1.98 (57%) FEV 1 1.70 (58%) FEV 1 /FVC.86 (100%) DL CO /V A 24 (110%) Neuro-muscular weakness or Thoracic deformity Abnormalities in TLC/DL CO 49 y/o woman TLC 4.81 (102%) FVC 2.90 (92%) FEV 1 2.37 (90%) FEV 1 /FVC.82 (100%) DL CO /V A 10 (42%) Pulmonary vascular disease Hyperinflation vs. combined defect Interpretation Algorithm Obstruction? FVC low Yes No Acceptable spirogram? FEV 1 /FVC ratio low Yes Pure obstruction? Reversible with Further testing* β agonist/ Incr NO Yes No Asthma COPD No No Obstruction? FVC low Yes No Prob. Restriction Normal Further testing* * lung volumes/dl CO Interpretation Algorithm: Lung Volumes and D L CO Total Lung Capacity Low NL D L CO D L CO Low* NL Low NL Interstitial process *D L /V A < ~100% pred S/p Resection Thoracic Deformity Muscle Weakness Obesity Pulmonary Vascular Disease Normal Summary Pulmonary function testing is an essential component of the evaluation of patients with respiratory complaints Spirometry can document obstruction (through the FEV 1 /FVC ratio) and suggest restriction Novel measures of exhaled gas may assist in the diagnosis of asthma Lung volumes and DLD CO are indicated to diagnose and differentiate restrictive and vascular abnormalities