Abstract
Gas exchange between organism and external ambient is the ultimate task of the respiratory system. Its efficiency is critically dependent on the efficiencies of ventilation and gas transport across the airspaces and lung tissues. Therefore, the knowledge of physiological principles underlying tests of lung function at different levels is basic to the understanding of the mechanisms limiting respiratory efficiency under different conditions, such as exercise and disease. The first step of lung function testing in clinical practice is spirometry, but it does not allow distinguishing the causes of airflow obstruction, i.e. airway disease versus emphysema, or establishing a diagnosis of lung restriction. Moreover, the effects of volume history and thoracic gas compressions may complicate its interpretation. Therefore, measurements of lung volumes are often necessary not only to confirm restriction in subjects with restrictive spirometric pattern but also for the assessment of lung hyperinflation. The latter may be due to either static (loss of elastic recoil) or dynamic (airflow limitation) mechanisms. The inhomogeneity of lung mechanics can be assessed by forced oscillations and/or nitrogen washout and may be more sensitive than spirometry to early obstruction of peripheral airways. The final step of lung function testing in clinical practice is the assessment of lung diffusing capacity for carbon monoxide. This test reflects the transport of gases from airspaces to blood across the alveolar-to-capillary barrier. Its interpretation is not always easy because the major resistance to carbon monoxide transfer is in the red cells rather than in the alveolar-to-capillary membrane.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agostoni E, Hyatt RE. Static behaviour of the respiratory system. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing. Section 3, part 1, vol. III. Bethesda: American Physiological Society; 1986. p. 113–30.
Loring SH, O'Donnell CR, Butler JP, et al. Transpulmonary pressures and lung mechanics with glossopharyngeal insufflation and exsufflation beyond normal lung volumes in competitive breath-hold divers. J Appl Physiol. 2007;102:841–6.
Seccombe LM, Rogers PG, Mai N, et al. Features of glossopharyngeal breathing in breath-hold divers. J Appl Physiol. 2006;101:799–801.
Gibson GJ, Pride NB, O'cain C, et al. Sex and age differences in pulmonary mechanics in normal nonsmoking subjects. J Appl Physiol. 1976;41:20–5.
Younes M, Kivinen G. Respiratory mechanics and breathing pattern during and following maximal exercise. J Appl Physiol. 1984;57:1773–82.
Woolcock AJ, Read J. Lung volumes in exacerbations of asthma. Am J Med. 1966;41:259–73.
Pride NB, Macklem PT. Lung mechanics in disease. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing. Section 3, part 2, vol. III. Bethesda: American Physiological Society; 1986. p. 659–92.
Leith DE, Mead J. Mechanisms determining residual volume of the lungs in normal subjects. J Appl Physiol. 1967;23:221–7.
Hutchinson J. On the capacity of the lungs, and on the respiratory movements, with the view of establishing a precise and easy method of detecting disease by the spirometer. Lancet. 1846;1:630–2.
Aaron SD, Dales RE, Cardinal P. How accurate is spirometry at predicting restrictive pulmonary impairment? Chest. 1999;115:869–73.
Vinegar A, Sinnett EE, Leith DE. Dynamic mechanisms determine functional residual capacity in mice, Mus musculus. J Appl Physiol. 1979;46:867–71.
Pellegrino R, Brusasco V, Rodarte JR, et al. Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol. 1993;74:2552–8.
Pellegrino R, Violante B, Nava S, et al. Relationship between expiratory airflow limitation and hyperinflation during methacholine-induced bronchoconstriction. J Appl Physiol. 1993;75:1720–7.
Duranti R, Filippelli M, Bianchi R, et al. Inspiratory capacity and decrease in lung hyperinflation with albuterol in COPD. Chest. 2002;122:2009–14.
Pepe PE, Marini JJ. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: the auto-PEEP effect. Am Rev Respir Dis. 1982;126:166–70.
Anthonisen NR. Tests of mechanical function. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing. Section 3, part 2, vol. III. Bethesda: American Physiological Society; 1986. p. 753–84.
DuBois AB, Botelho SY, Comroe JH Jr. A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. J Clin Invest. 1956;35:327–35.
Miller RD, Offord KP. Roentgenologic determination of total lung capacity. Mayo Clin Proc. 1980;55:694–9.
Krayer S, Rehder K, Beck KC, et al. Quantification of thoracic volumes by three-dimensional imaging. J Appl Physiol. 1987;62:591–8.
Rodenstein DO, Stănescu DC. Reassessment of lung volume measurement by helium dilution and by body plethysmography in chronic air-flow obstruction. Am Rev Respir Dis. 1982;126:1040–4.
O'Donnell CR, Bankier AA, Stiebellehner L, et al. Comparison of plethysmographic and helium dilution lung volumes: which is best for COPD? Chest. 2010;137:1108–15.
Shore SA, Huk O, Mannix S, et al. Effect of panting frequency on the plethysmographic determination of thoracic gas volume in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1983;128:54–9.
Rodarte JR, Rehder K. Dynamics of respiration. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing. Section 3, part 1, vol. III. Bethesda: American Physiological Society; 1986. p. 131–44.
Peslin R, Fredberg JJ. Oscillation mechanics of the respiratory system. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing. Section 3, part 1, vol. III. Bethesda: American Physiological Society; 1986. p. 145–77.
Peslin R, Felicio da Silva J, et al. Respiratory mechanics studied by forced oscillations during artificial ventilation. Eur Respir J. 1993;6:772–84.
Dellacà RL, Santus P, Aliverti A, et al. Detection of expiratory flow limitation in COPD using the forced oscillation technique. Eur Respir J. 2004;23:232–40.
Hyatt RE, Wilcox RE. Extrathoracic airway resistance in man. J Appl Physiol. 1961;16:326–30.
Mead J, Whittenberger JL. Evaluation of airway interruption technique as a method for measuring pulmonary air-flow resistance. J Appl Physiol. 1954;6:408–16.
Yanai M, Sekizawa K, Ohrui T, et al. Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol. 1992;72:1016–23.
Brusasco V, Warner DO, Beck KC, et al. Partitioning of pulmonary resistance in dogs: effect of tidal volume and frequency. J Appl Physiol. 1989;66:1190–6.
Tiffeneau R, Pinelli A. Régulation bronchique de la ventilation pulmonaire. J Fr Med Chir Thorac. 1948;2:221–44.
Hyatt RE, Schilder DP, Fry DL. Relationship between maximum expiratory flow and degree of lung inflation. J Appl Physiol. 1958;13:331–6.
Hyatt RE. Forced expiration. In: Macklem PT, Mead J, editors. Handbook of physiology, The respiratory system. Mechanics of breathing, Section 3, part 1, vol. III. Bethesda: American Physiological Society; 1986. p. 295–314.
Permutt S, Riley RL. Hemodynamics of collapsible vessels with tone: the vascular waterfall. J Appl Physiol. 1963;18:924–32.
Mead J, Turner JM, Macklem PT, et al. Significance of the relationship between lung recoil and maximum expiratory flow. J Appl Physiol. 1967;22:95–108.
Dawson SV, Elliott EA. Wave-speed limitation on expiratory flow – a unifying concept. J Appl Physiol. 1977;43:498–515.
Quanjer PH, Weiner DJ, Pretto JJ, et al. Measurement of FEF 25–75% and FEF 75% does not contribute to clinical decision making. Eur Respir J. 2014;43:1051–8.
Schilder DP, Roberts A, Fry DL. Effects of gas density and viscosity on the maximal expiratory flow-volume relationships. J Clin Invest. 1963;42:1705–13.
Meadows JA 3rd, Rodarte JR, Hyatt RE. Density dependence of maximal expiratory flow in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1980;121:47–53.
Davis J, Schroter RC, Sudlow MF. The investigation of the effects of gas density and viscosity on the physics of flow in small airways during forced expiration. J Physiol. 1972;223:9P–10P.
Nadel JA, Thierney DF. Effect of a previous deep inspiration on airway resistance in man. J Appl Physiol. 1961;16:717–9.
Lim TK, Ang SM, Rossing TH, et al. The effects of deep inhalation on maximal expiratory flow during intensive treatment of spontaneous asthmatic episodes. Am Rev Respir Dis. 1989;140:340–3.
Fairshter RD. Effect of a deep inspiration on expiratory flow in normals and patients with chronic obstructive pulmonary disease. Bull Eur Physiopathol Respir. 1986;22:119–25.
Ingram RH Jr, Schilder DP. Effect of gas compression on pulmonary pressure, flow, and volume relationship. J Appl Physiol. 1966;21:1821–6.
Pellegrino R, Antonelli A, Crimi E, et al. Dependence of bronchoconstrictor and bronchodilator responses on thoracic gas compression volume. Respirology. 2014;19:1040–5.
Pellegrino R, Brusasco V. Lung hyperinflation and flow limitation in chronic airway obstruction. Eur Respir J. 1997;10:543–9.
Ninane V, Leduc D, Kafi SA, et al. Detection of expiratory flow limitation by manual compression of the abdominal wall. Am J Respir Crit Care Med. 2001;163:1326–30.
Koulouris NG, Valta P, Lavoie A, et al. A simple method to detect expiratory flow limitation during spontaneous breathing. Eur Respir J. 1995;8:306–13.
Hage R, Aerts JGJV, Verbraak AFM, et al. Detection of flow limitation during tidal breathing by the interruptor technique. Eur Resp J. 1995;8(11):1910–4.
Miller RD, Hyatt RE. Obstructing lesions of the larynx and trachea: clinical and physiologic characteristics. Mayo Clin Proc. 1969;44:145–61.
Storey WF, Staub NC. Ventilation of terminal air units. J Appl Physiol. 1962;17:391–7.
Engel LA, Anthonisen NR. Demonstration of airway closure in man. J Appl Physiol. 1975;38:1117–25.
Fowler WS. Lung function studies. III. Uneven pulmonary ventilation on normal subjects and in patients with pulmonary disease. J Appl Physiol. 1949;2:283–99.
Comroe JH Jr, Fowler WS. Lung function studies. VI Detection of uneven alveolar ventilation during a single breath of oxygen. Am J Med. 1951;10:408–13.
Prisk GK. Microgravity and the lung. J Appl Physiol. 2000;89:385–96.
Cosio M, Ghezzo H, Hogg JC, et al. The relations between structural changes in small airways and pulmonary function tests. N Engl J Med. 1978;298:1277–81.
Milic-Emili J, Torchio R, D'Angelo E. Closing volume: a reappraisal (1967–2007). Eur J Appl Physiol. 2007;99:567–83.
Darling RC, Cournand A, Mansfield JS, et al. Studies on the intrapulmonary mixture of gases. I. Nitrogen elimination from blood and body tissues during high oxygen breathing. J Clin Invest. 1940;19:591–7.
Becklake MR. A new index of the intrapulmonary mixture of inspired air. Thorax. 1952;7:111–6.
Bouhuys A. Pulmonary nitrogen clearance in relation to age in healthy males. J Appl Physiol. 1963;18:297–300.
Oude Engberink E, Ratjen F, Davis SD, et al. Inter-test reproducibility of the lung clearance index measured by multiple breath washout. Eur Respir J. 2017;5(50):1700433.
Gustafsson PM, Aurora P, Lindblad A. Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis. Eur Respir J. 2003;22:972–9.
Crawford AB, Makowska M, Paiva M, et al. Convection- and diffusion-dependent ventilation maldistribution in normal subjects. J Appl Physiol. 1985;59:838–46.
Verbanck S, Paiva M. Gas mixing in the airways and airspaces. Compr Physiol. 2011;1:809–34.
Weibel ER, Federspiel WJ, Fryder-Doffey F, et al. Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity. Respir Physiol. 1993;93:125–49.
Scheid P, Piiper J. Diffusion. In: Crystal RG, West JB, Weibel ER, Barnes PJ, editors. The lung: scientific foundations. Philadelphia, PA: Lippincott-Raven; 1997. p. 1681–071.
Hsia CC, Wagner PD, Dane DM, et al. Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing capacity in exercising foxhounds. J Appl Physiol. 2008;105:1441–7.
Cotes JE, Dabbs JM, Elwood PC, et al. Iron-deficiency anemia: its effect on transfer factor for the lung (diffusing capacity) and ventilation and cardiac frequency during submaximal exercise. Clin Sci. 1972;42:325–35.
Krogh M. The diffusion of gases through the lungs of man. J Physiol. 1915;49:271–300.
Blakemore WS, Forster RE, Morton JW, et al. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957;36:1–17.
Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 2017;1600016:49.
Stanojevic S, Graham BL, Cooper BG, et al. Official ERS technical standards: global lung function initiative reference values for the carbon monoxide transfer factor for Caucasians. Eur Respir J. 2017;50:1700010.
Hughes JM, Pride NB. In defence of the carbon monoxide transfer coefficient Kco (TL/VA). Eur Respir J. 2001;17:168–74.
Roughton FJ, Forster RE. Relative importance of diffusion and chemical reaction rates in determining the rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J Appl Physiol. 1957;11:290–302.
Hsia CC, McBrayer DG, Ramanathan M. Reference values of pulmonary diffusing capacity during exercise by a rebreathing technique. Am J Respir Crit Care Med. 1995;152:658–65.
Carlsen E, Comroe JH Jr. The rate of uptake of carbon monoxide and of nitric oxide by normal human erythrocytes and experimentally produced spherocytes. J Gen Physiol. 1958;42:83–107.
Guénard H, Varène N, Vaida P. Determination of lung capillary blood volume and membrane diffusing capacity by measurement of NO and CO transfer. Respir Physiol. 1987;70:113–20.
Borland CD, Higenbottam TW. A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide. Eur Respir J. 1989;2:56–63.
Borland C, Bottrill F, Jones A, et al. The significant blood resistance to lung nitric oxide transfer lies within the red cell. J Appl Physiol. 2014;116:32–41.
Barisione G, Brusasco C, Garlaschi A, et al. Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias. J Appl Physiol. 2016;120:1029–38.
Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948–68.
Stam H, Hrachovina V, Stijnen T, et al. Diffusing capacity dependent on lung volume and age in normal subjects. J Appl Physiol. 1994;76:2356–63.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Brusasco, V., Barisione, G. (2019). Tests of Lung Function: Physiological Principles and Interpretation. In: Cogo, A., Bonini, M., Onorati, P. (eds) Exercise and Sports Pulmonology. Springer, Cham. https://doi.org/10.1007/978-3-030-05258-4_3
Download citation
DOI: https://doi.org/10.1007/978-3-030-05258-4_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-05257-7
Online ISBN: 978-3-030-05258-4
eBook Packages: MedicineMedicine (R0)