European Respiratory Society
Lung Function Testing

Although diagnosis always begins with a careful history and physical examination and a physician is obligated to consider more than the diseased organ, testing of lung function has become standard practice to confirm the diagnosis, evaluate the severity of respiratory impairment, assess the therapy response and follow-up patients with various cardio-respiratory disorders. Ventilation, diffusion, blood flow and control of breathing are the major components of respiration and one or more of these functional components can be affected by any disorder. Frequently, no single pulmonary function test yields all the information in an individual patient and multiple tests have to be combined to allow proper evaluation. The pulmonary function laboratory is therefore very important in pulmonary medicine to provide accurate and timely results of lung function tests. This issue of the European Respiratory Monograph not only offers the reader a state-of-the-art approach to pulmonary function testing, but also contributes significantly to a better understanding of the pathophysiological processes underlying various diseases and contributing to the morbidity of patients.

  1. Page vii
  2. Page viii
  3. Page 1
    Correspondence: P. Enright, 4460 East Ina Road, Tucson, AZ 85718, USA.

    Office spirometry in the primary care setting can be most helpful for the detection (case finding) and management of asthma and chronic obstructive pulmonary disease (COPD). The severity of asthma is underestimated by history and physical examination alone in some patients. Only spirometry has been shown to detect COPD in its early stages. The cost and side-effects of medications for asthma and COPD drives the need for objective measurement of their response, by measuring the forced expiratory volume in one second during follow-up visits. The value of population-based screening for these diseases needs further evidence. The new generation of office spirometers are less expensive, include quality checks, and make spirometry easier using six second manoeuvres. However, enthusiastic coaching for correct breathing manoeuvres remains important to reduce the risk of misclassification, which is substantial in the primary care setting.

  4. Page 15
    Correspondence: M.D. Goldman, David Geffen School of Medicine, University of California, Los Angeles, USA.

    The aim of this chapter has been to describe the unique and clinically relevant information provided by whole-body plethysmography. Primary among this information is the measurement of absolute TGV. Plethysmographic TGV (FRCpleth) is considered the gold standard of absolute volume measurements and includes the nonventilated airspace. Because the whole-body plethysmograph provides a measure of true change in TGV, an increased use of the combination pressure-corrected integrated-flow (transmural) plethysmograph is to be expected in the evaluation of patients with chronic airflow obstruction. The use of thoracic volume measurements rather than integrated mouth flow has provided more precise characterisation of pulmonary mechanical parameters as a function of lung volume.

    The clinical measurement of plethysmographic airflow resistance is also considered to be the gold standard, and is more widely applied than either pulmonary resistance measured invasively via oesophageal balloon or forced oscillatory resistance measured noninvasively. It is emphasised that the plethysmographic measurement of resistance requires two separate measurements: first, that of sRaw, and secondly, the measurement of TGV itself. Both plethysmographic and forced oscillatory resistance are influenced by the subject's spontaneous breathing pattern and both require further complementary measurements to define more precisely the extent of pathophysiological disturbances in patients with chronic airflow obstruction. Measurement of resistance as a function of lung volume provides a useful extension of currently utilised methodology and more clearly delineates effects of small airway obstruction.

    Technological developments have now permitted incorporation of the transmural function in commercially manufactured plethysmographs, thereby expanding the utility of whole-body plethysmography, and increasing its utility in distinguishing between flow resistive and compression effects, both dynamic airway compression and airway closure (nonventilated airspaces). While this capability has hitherto been utilised primarily in FVC efforts, increased interest in new treatments for COPD may stimulate use of this capability during tidal breathing. Whole-body plethysmography may be further developed to include measurement of TGV during tidal breathing without panting efforts against a closed airway shutter, and measurement of instantaneous Raw during tidal breathing.

    The sensitivity of plethysmography imposes demands for vigilance on the operator, who must ensure stable body posture, attention to physical support of the oral cavity and cooperation of the subject during testing procedures. Cooperation may be improved by careful instructions to the patient, careful attention to the patient during testing and informing the patient that they can remove the mouthpiece if breathing becomes obstructed or too difficult. Posture must be supported to maintain subject comfort and the instrument mouthpiece must be brought to an appropriate level for the subject to avoid unusual neck posture. The usual clinical testing procedure of at least three replicate measures may be usefully augmented by increased testing replicates in circumstances where acute response to intervention is desired.

  5. Page 44
    Correspondence: P.M.A. Calverley, University Hospital Aintree, Liverpool, UK.

    The maintenance of blood gas homeostasis is dependent on the balance between respiratory drive and peripheral, mechanical and chemoreceptor responses. No single measurement encapsulates all aspects of this complex control system. Most investigators and clinical tests rely on relatively short-term changes in inspired gas concentrations and/or additional predominantly inspiratory mechanical loading to determine how the control system responds. Usually ventilation or an index of neural drive, such as mouth occlusion pressure, is used as the output measurement. Changes in the mechanical properties of the lungs make interpretation of these tests difficult and in common diseases such as chronic obstructive pulmonary disease, asthma and interstitial lung diseases the usual index of ventilatory control abnormality is a change in the arterial blood gas tension. In some conditions, e.g. hypo- or hyperventilation syndromes, investigation of respiratory control mechanisms may be useful. Studies of disordered respiratory control have helped understanding of the pathophysiology of disease and continue to inform current clinical practice, e.g. in the prescription of high-flow oxygen. Future developments using modern computerised methods to analyse breathing pattern and relate this to neural activation may offer more appropriate clinical tools.

  6. Page 57
    Correspondence: T. Troosters, Respiratory Division and Respiratory Rehabilitation, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium.

    Respiratory muscle weakness has serious clinical consequences. The assessment of respiratory muscle function and the detection of respiratory muscle weakness has a place in the clinical decision tree of many diseases, including lung disease, neuromuscular diseases and others. Equipment to measure respiratory muscle strength has become available and assessment of respiratory muscle force through the assessment of maximal in- and expiratory pressures at the mouth (PI,max, PE,max), has become a routine assessment in many lung function laboratories. In rare cases more elaborate measurements, including transdiaphragmatic pressures, cough pressures or measurements applying electrical or magnetical stimulation of the phrenic nerve, can be helpful in the diagnostic process. Clinicians should be aware that respiratory muscle force is approached indirectly by measuring the pressure generated by the respiratory pump. The mechanics of the pump should be taken into account when interpreting the results. Normal values are available, but large variability is present. Part of this variability is explained by the methodological differences described in this chapter.

    Nevertheless, since respiratory muscle weakness can be treated in many cases by respiratory muscle training, or tapering of treatment with drugs that may induce respiratory muscle weakness (e.g. corticosteroids) or may help clinicians decide on mechanical ventilation strategies, knowledge of respiratory muscle dysfunction opens a window of clinical treatment opportunities. Hence, properly performed assessment of respiratory muscle function should be possible in any well-equipped lung function laboratory.

  7. Page 72
    Correspondence: H.J. Smith, Research in Respiratory Diagnostics, Bahrendorfer Str. 3, 12555 Berlin, Germany.

    The aim of this chapter has been to describe the unique and clinically relevant information that forced oscillation technique (FOT) provides. This may be derived without mathematical mastery of technological principles of the equipment and/or of numerical models. It is emphasised that recognition of the change in respiratory mechanical parameters as a function of oscillation frequency is necessary to appreciate the outstanding value of FOT in its ability to assess peripheral airway function. This has been one of the major challenges in respiratory diagnostics up to the present time.

    The short duration of the FOT test, 20–30 s, makes it particularly useful as part of a diagnostic programme of lung function testing; it is not suggested that FOT be used in lieu of conventional pulmonary function testing, but rather in addition. FOT measures resting breathing while spirometry assesses maximal respiratory performance of the patient. The special value of FOT in terms of short-term response to bronchial and therapeutic challenge has been emphasised as well as its value in monitoring long-term trend responses to therapy.

    The simplicity of FOT measurements and its minimal requirements on subject cooperation are in rather sharp contrast to its current limited clinical acceptance. Two primary reasons for the present limited application of FOT include the need for viewing respiratory mechanical parameters over a range of frequencies and the resultant central-peripheral specificity of oscillatory parameters, with specific emphasis on the reflection of peripheral airway function by low-frequency reactance. Indeed, lack of awareness of this ability of FOT to assess peripheral airway function has turned physicians to the use of multiple replicates of high-resolution computed tomography lung scans to assess small airway function. Other reasons for limited use of FOT currently may include the greater variability of FOT measures compared with spirometry. Despite such variability, use of at least three replicate FOT measures combined with therapeutic challenge can provide sensitive evaluation of small airway function.

    The freedom allowed to the subject to breathe “naturally” imposes increased demands for vigilance on the operator, who must maintain a quiet environment for forced oscillation technique testing. Operators must also reassure subjects that their relaxation is needed, except for the facial musculature ensuring tight lip closure on the mouthpiece. Posture must be supported to maintain subject comfort and the instrument mouthpiece must be brought to the subject to avoid stretching of the neck. Finally, the availability of results from a brief test must not lead the operator to accept a single measurement, but rather, the usual clinical testing procedure of at least three replicate measures is required.

  8. Page 106
    Correspondence: J.M.B. Hughes, 4 Cedars Road, London SW13 0HP, UK.
    1. 1.

      The arterial oxygen tension (Pa,O2) in normal subjects is affected by several factors, principally age, altitude and the inspired oxygen fraction (FI,O2). The arterial carbon dioxide tension (Pa,CO2) is not affected by age, but is lowered by the hyperventilation of pregnancy and by anxiety. In arterial blood 98–99% of oxygen is bound to haemoglobin (Hb). Pulse oximetry is a simple noninvasive way of estimating the oxygen saturation of Hb in arterial blood (Sa,O2) [normal=97.5%]. In anaemia, with Hb concentration 50% normal, Sa,O2 and Pa,O2 will be normal, but arterial oxygen content (Ca,O2) will be only 50%.

    2. 2.

      The commonest clinical cause (in 90% of cases) of a low Pa,O2 is uneven distribution of alveolar ventilation (V′A) and perfusion (Q′), so-called V′A/Q′ mismatch. The cause is intrapulmonary disease affecting the bronchi, alveoli and/ or pulmonary circulation. The second cause (in 8%) is extrapulmonary (e.g. respiratory muscle weakness, loss of CO2 chemosensitivity), involving insufficient total ventilation, often with a tidal volume that is too small to clear the obligatory anatomic dead space completely.

    3. 3.

      In chronic respiratory failure, the Pa,O2 and Sa,O2 are severely reduced (Pa,CO2 may be low, normal or high). In acute respiratory failure, often associated with shallow breathing and an extrapulmonary cause, the Pa,CO2 is usually raised as much as the Pa,O2 is lowered. An increase in FI,O2 restores Pa,O2 to a “normal” level for air breathing, whatever the cause of the respiratory failure. In the acute on chronic respiratory failure of chronic obstructive pulmonary disease (COPD), an FI,O2 increase may exacerbate the shallow breathing and lead to a further rise in Pa,CO2.

    4. 4.

      The relationship between the oxygen content (CO2) of blood and its partial pressure (PO2) – the oxygen dissociation curve (ODC) – is sigmoid in shape. The position of the curve on the PO2 axis is defined by the PO2 at half maximum blood oxygen concentration (∼SO2 50%) - the P50). A left shift (low P50) promotes oxygen loading in the lung, and a right shift increases oxygen unloading to the tissues. Both may be advantageous in the right circumstances – the left shift in the foetus, and at extreme altitude (though the left shift in carbon monoxide poisoning may be fatal), and the right shift in strenuous exercise.

    5. 5.

      The normal range for Pa,O2 is quite wide. The “efficiency” of pulmonary gas exchange is often assessed, on a quantitative basis, in terms of a physiological dead space/tidal volume ratio (VD/VT), reflecting abnormally high V′A/Q′ ratios, physiological shunt (Q′s/Q′T) or alveolar–arterial oxygen tension gradients (A–a PO2), reflecting the low V′A/Q′ units.

    6. 6.

      Apart from V′A/Q′ mismatch and hypoventilation, a low Pa,O2 can be caused by diffusion limitation or an anatomic shunt (either intrapulmonary or intracardiac). The hepatopulmonary syndrome (HPS), with microvascular dilatations, is an example of a low Pa,O2, which could be due to either or both of these causes, depending on one’s point of view.

    7. 7.

      The passage of oxygen from terminal bronchioles to red cells is principally by molecular diffusion, the final step being chemical combination with intra-red cell Hb. The process is super-efficient, and only breaks down clinically when the surface area for exchange is reduced by alveolar destruction (a low oxygen diffusing capacity (DL,O2)) and pulmonary blood flow (∼cardiac output) is high (e.g. on exercise), giving a low DL/Q′ ratio.

    8. 8.

      The multiple inert gas elimination technique (MIGET) is a research tool for measuring V′A/Q′ distribution in a 50 compartment model of the lung, which gives insights into the pathogenesis of intrapulmonary disease.

  9. Page 127
    Correspondence: H. Stam, Pulmonary Function Dept, Dept Pulmonary Diseases, Erasmus Medical Centre, Erasmus University, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

    The main function of the lungs is to establish exchange of O2 and CO2 between the environment and the capillary blood. The gas transport across the alveolar-capillary membrane can be measured by the transfer of carbon monoxide (CO). CO has a high affinity for haemoglobin and is assumed to be absent in pulmonary capillary blood. After inspiration, CO diffuses by the partial CO pressure gradient over the gas–blood barrier from the alveoli into the capillary blood and disappears from the alveolar gas. The decrease in CO fraction in the alveolar gas in a fixed time interval quantifies the diffusing capacity of the lung. As not only diffusion but also chemical reactions affect the CO transfer, the term “transfer” (T) rather than diffusion (D) is used. Traditionally, gas transfer across the alveolo-capillary membrane is described in the USA by the diffusing capacity for CO (DL,CO) and in Europe it is called the transfer factor (TL,CO). However, DL,CO and TL,CO describe the same variable and are interchangeable. Methods to determine the transfer factor TL,CO are the single breath, the intrabreath and multiple breath methods. Each has its advantages and limitations. The most important limitation of the single breath technique is the required lung volume. Vital capacity (VC) has to be >1.5 L in order to obtain reliable results. Traditional single breath measurements are inaccurate in the case of severe airway obstruction due to inadequate time for equilibration of gases in the lung. Using equipment that is based on fast responding gas analysers, conclusions of unequal distribution of the diffusion characteristics may be drawn. A minimal VC of 1.5 L is not required when using fast gas analysers. At reduced lung volume TL,CO/VA increases and this may lead to erroneous interpretation of data in patients with a restrictive lung disease. For the interpretation, it is important to take the possible influence of a reduced VA or the influence of severe airway obstruction into consideration. In patients who are not able to perform the single breath test and in small children the transfer factor is determined with multiple breath methods. From the multiple breath methods the rebreathing method is traditionally performed during hyperventilation. Patients who are too ill to perform a single breath test, will also have problems with a hyperventilation procedure. Therefore, a rebreathing method during normal, spontaneous ventilation was developed. When measuring the rebreathing transfer factor during rest ventilation, it is important to realise that results are dependent on alveolar ventilation and alveolar volume.

    To minimise the variability in the diffusion measurement it is important to standardise these tests with respect to e.g. haemoglobin correction, body position, effect of O2etc. An important step forward is the use of European Respiratory Society/American Thoracic Society guidelines.

  10. Page 146
    Correspondence: J. Roca, Servei de Pneumologia, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain.

    The role of the O2 transport/O2 utilisation system determining maximum O2 uptake has been analysed in an integrative manner. The system responses to exercise in healthy subjects (athletes and sedentary) and in common pulmonary diseases have been examined. Finally, basic principles of exercise testing and interpretation of the results have been reviewed.

  11. Page 166
    Correspondence: P.J.F.M. Merkus, Division of Respiratory Medicine, Dept of Paediatrics, Sophia Children's Hospital – Erasmus Medical Centre, PO Box 2060, 3000 CB Rotterdam, the Netherlands.
    • Measurements of ventilatory function can be carried out in children of almost all ages, except between 2–3 yrs of age, which remains a very difficult age group to assess.

    • The type of measurements that are feasible strongly depends on developmental age of the child, always requiring considerably more time and effort than measurements in adults

    • Methodological guidelines exist for most measurements in infants and schoolchildren, and are being developed for preschool children

    • It is strongly recommended to work according to published guidelines, and to choose appropriate reference equations

    • Reliable reference data need to be established for young children aged <7 yrs. Prediction of values for such children should never be based on those extrapolated from older subjects.

  12. Page 195
    Correspondence: A. Rossi, Unità Operativa Pneumologia, Ospedali Riuniti, Largo Barozzi 1, I-24128 Bergamo, Italy.

    Assessment of respiratory mechanics can play a central role in the management of critically ill patients undergoing artificial ventilation because of acute respiratory failure (ARF). This assessment is of crucial importance to understand the pathophysiology of the disease underlying ARF and to improve the patient–ventilator interaction and the medical treatment of the disease.

    Despite the great importance of monitoring lung mechanics in ventilator-dependent patients, these measurements are not regularly performed.

    The purpose of this chapter is to review briefly the most common methods and techniques for measuring and monitoring respiratory mechanics on-line and off-line at the bedside of the patient in the intensive care unit (ICU) and to be persuasive about the usefulness and the feasibility of monitoring respiratory mechanics in the congested rooms of the ICU. The chapter includes a three point analysis: 1) measurements during controlled mechanical ventilation, i.e. in the relaxed, passive patients; 2) evaluation of respiratory mechanics during assisted mechanical ventilation; 3) the issue of the patient's evaluation in the weaning process from mechanical ventilation.