Skip to main content

Tests of Lung Function: Physiological Principles and Interpretation

  • Chapter
  • First Online:
Exercise and Sports Pulmonology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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.

    Google Scholar 

  2. 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.

    PubMed  Google Scholar 

  3. Seccombe LM, Rogers PG, Mai N, et al. Features of glossopharyngeal breathing in breath-hold divers. J Appl Physiol. 2006;101:799–801.

    PubMed  Google Scholar 

  4. 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.

    CAS  PubMed  Google Scholar 

  5. Younes M, Kivinen G. Respiratory mechanics and breathing pattern during and following maximal exercise. J Appl Physiol. 1984;57:1773–82.

    CAS  PubMed  Google Scholar 

  6. Woolcock AJ, Read J. Lung volumes in exacerbations of asthma. Am J Med. 1966;41:259–73.

    CAS  PubMed  Google Scholar 

  7. 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.

    Google Scholar 

  8. Leith DE, Mead J. Mechanisms determining residual volume of the lungs in normal subjects. J Appl Physiol. 1967;23:221–7.

    CAS  PubMed  Google Scholar 

  9. 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.

    Google Scholar 

  10. Aaron SD, Dales RE, Cardinal P. How accurate is spirometry at predicting restrictive pulmonary impairment? Chest. 1999;115:869–73.

    CAS  PubMed  Google Scholar 

  11. Vinegar A, Sinnett EE, Leith DE. Dynamic mechanisms determine functional residual capacity in mice, Mus musculus. J Appl Physiol. 1979;46:867–71.

    CAS  PubMed  Google Scholar 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. 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.

    CAS  PubMed  Google Scholar 

  14. Duranti R, Filippelli M, Bianchi R, et al. Inspiratory capacity and decrease in lung hyperinflation with albuterol in COPD. Chest. 2002;122:2009–14.

    CAS  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

  16. 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.

    Google Scholar 

  17. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Miller RD, Offord KP. Roentgenologic determination of total lung capacity. Mayo Clin Proc. 1980;55:694–9.

    CAS  PubMed  Google Scholar 

  19. Krayer S, Rehder K, Beck KC, et al. Quantification of thoracic volumes by three-dimensional imaging. J Appl Physiol. 1987;62:591–8.

    CAS  PubMed  Google Scholar 

  20. 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.

    CAS  PubMed  Google Scholar 

  21. 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.

    PubMed  Google Scholar 

  22. 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.

    CAS  PubMed  Google Scholar 

  23. 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.

    Google Scholar 

  24. 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.

    Google Scholar 

  25. Peslin R, Felicio da Silva J, et al. Respiratory mechanics studied by forced oscillations during artificial ventilation. Eur Respir J. 1993;6:772–84.

    CAS  PubMed  Google Scholar 

  26. 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.

    PubMed  Google Scholar 

  27. Hyatt RE, Wilcox RE. Extrathoracic airway resistance in man. J Appl Physiol. 1961;16:326–30.

    CAS  PubMed  Google Scholar 

  28. 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.

    CAS  PubMed  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

  31. Tiffeneau R, Pinelli A. Régulation bronchique de la ventilation pulmonaire. J Fr Med Chir Thorac. 1948;2:221–44.

    CAS  PubMed  Google Scholar 

  32. Hyatt RE, Schilder DP, Fry DL. Relationship between maximum expiratory flow and degree of lung inflation. J Appl Physiol. 1958;13:331–6.

    CAS  PubMed  Google Scholar 

  33. 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.

    Google Scholar 

  34. Permutt S, Riley RL. Hemodynamics of collapsible vessels with tone: the vascular waterfall. J Appl Physiol. 1963;18:924–32.

    CAS  PubMed  Google Scholar 

  35. 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.

    CAS  PubMed  Google Scholar 

  36. Dawson SV, Elliott EA. Wave-speed limitation on expiratory flow – a unifying concept. J Appl Physiol. 1977;43:498–515.

    CAS  PubMed  Google Scholar 

  37. 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.

    PubMed  Google Scholar 

  38. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 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.

    PubMed  Google Scholar 

  40. 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.

    CAS  PubMed  Google Scholar 

  41. Nadel JA, Thierney DF. Effect of a previous deep inspiration on airway resistance in man. J Appl Physiol. 1961;16:717–9.

    CAS  PubMed  Google Scholar 

  42. 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.

    CAS  PubMed  Google Scholar 

  43. 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.

    CAS  PubMed  Google Scholar 

  44. Ingram RH Jr, Schilder DP. Effect of gas compression on pulmonary pressure, flow, and volume relationship. J Appl Physiol. 1966;21:1821–6.

    PubMed  Google Scholar 

  45. Pellegrino R, Antonelli A, Crimi E, et al. Dependence of bronchoconstrictor and bronchodilator responses on thoracic gas compression volume. Respirology. 2014;19:1040–5.

    PubMed  Google Scholar 

  46. Pellegrino R, Brusasco V. Lung hyperinflation and flow limitation in chronic airway obstruction. Eur Respir J. 1997;10:543–9.

    CAS  PubMed  Google Scholar 

  47. 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.

    CAS  PubMed  Google Scholar 

  48. 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.

    CAS  PubMed  Google Scholar 

  49. 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.

    CAS  Google Scholar 

  50. Miller RD, Hyatt RE. Obstructing lesions of the larynx and trachea: clinical and physiologic characteristics. Mayo Clin Proc. 1969;44:145–61.

    CAS  PubMed  Google Scholar 

  51. Storey WF, Staub NC. Ventilation of terminal air units. J Appl Physiol. 1962;17:391–7.

    CAS  PubMed  Google Scholar 

  52. Engel LA, Anthonisen NR. Demonstration of airway closure in man. J Appl Physiol. 1975;38:1117–25.

    CAS  PubMed  Google Scholar 

  53. 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.

    CAS  PubMed  Google Scholar 

  54. 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.

    PubMed  Google Scholar 

  55. Prisk GK. Microgravity and the lung. J Appl Physiol. 2000;89:385–96.

    CAS  PubMed  Google Scholar 

  56. 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.

    CAS  PubMed  Google Scholar 

  57. Milic-Emili J, Torchio R, D'Angelo E. Closing volume: a reappraisal (1967–2007). Eur J Appl Physiol. 2007;99:567–83.

    PubMed  Google Scholar 

  58. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Becklake MR. A new index of the intrapulmonary mixture of inspired air. Thorax. 1952;7:111–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Bouhuys A. Pulmonary nitrogen clearance in relation to age in healthy males. J Appl Physiol. 1963;18:297–300.

    CAS  PubMed  Google Scholar 

  61. 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.

    Google Scholar 

  62. 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.

    CAS  PubMed  Google Scholar 

  63. Crawford AB, Makowska M, Paiva M, et al. Convection- and diffusion-dependent ventilation maldistribution in normal subjects. J Appl Physiol. 1985;59:838–46.

    CAS  PubMed  Google Scholar 

  64. Verbanck S, Paiva M. Gas mixing in the airways and airspaces. Compr Physiol. 2011;1:809–34.

    PubMed  Google Scholar 

  65. 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.

    CAS  PubMed  Google Scholar 

  66. 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.

    Google Scholar 

  67. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 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.

    CAS  PubMed  Google Scholar 

  69. Krogh M. The diffusion of gases through the lungs of man. J Physiol. 1915;49:271–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 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.

    Google Scholar 

  72. 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.

    PubMed  Google Scholar 

  73. Hughes JM, Pride NB. In defence of the carbon monoxide transfer coefficient Kco (TL/VA). Eur Respir J. 2001;17:168–74.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  75. 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.

    CAS  PubMed  Google Scholar 

  76. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 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.

    PubMed  Google Scholar 

  78. 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.

    CAS  PubMed  Google Scholar 

  79. 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.

    PubMed  Google Scholar 

  80. 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.

    PubMed  Google Scholar 

  81. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948–68.

    CAS  PubMed  Google Scholar 

  82. 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.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vito Brusasco .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

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)

Publish with us

Policies and ethics