Pulmonary function testing: Applying techniques in infants

Pulmonary function testing is an important part of the evaluation of patients with respiratory signs and symptoms. Until recently, such testing was restricted to adults and children who were old enough to cooperate with the required maneuvers. However, certain techniques can be useful in the assessment and treatment of young children and infants with respiratory disease.

Pulmonary function tests have not been widely used in infants for several reasons, including the need for specialized equipment, which frequently is assembled only in specialized centers, and the need for experienced personnel and extended time for testing. Several of the techniques require sedation, and some require placement of an esophageal catheter to estimate pleural pressure; thus, these tests are considered invasive.

Infants are commonly sedated with the hypnotic chloral hydrate, which can provide up to several hours of sleep while maintaining spontaneous respirations. This sedation, although quite safe, requires careful monitoring of vital signs during testing by personnel trained in airway management and resuscitation.

Pulmonary function tests may have many applications in infants and young children with respiratory disease; these applications are generally the same as those in older children.¹ The most common uses include documenting the presence of disease states (such as obstructive or restrictive disease) and determining the most appropriate treatment (for example, bronchodilators or diuretics).

In addition, serial measurements may help predict the course of a disease such as cystic fibrosis. Finally, pulmonary function tests in infants can provide information about normal lung and airway growth, an area that has been poorly understood.

In this article, we will review the techniques that are used in pulmonary function testing in infants and young children.

Tidal breathing analysis

These tests involve measurements that can be made during spontaneous breathing. Advantages of tidal breathing tests are that they are noninvasive and do not require special maneuvers by the infant.

The most common method involves placement of a mask, to which a pneumotachograph is connected, over the infant's face to measure airflow. Volume (such as tidal volume [Vt]) is calculated by integrating the flow signal with time.

An alternative method of measuring tidal breathing involves respiratory inductive plethysmography. This technique uses coiled wires within 2 sets of elastic bands that encircle the chest and abdomen. A small electrical current is passed through the wires, and changes in a cross-sectional area of the abdomen and rib-cage compartments result in a change in conductance through the wires.

This change in conductance is proportional to the change in volume of each compartment, the sum of which reflects the Vt. Flow can be calculated by mathematically differentiating the volume-time signal.

Respiratory inductive plethysmography does not require placement of a mask over the infant's mouth or sedation and therefore can be used for prolonged data collection. Parameters related to the timing of the respiratory cycle can be measured from a flow-time, volume-time, or flow-volume waveform and can be derived by either of these techniques (Figure 1).

From volume-time tracings, variables such as respiration rate, Vt, inspiratory time, expiratory time (Te), and total respiratory cycle time can be measured. Flow-time tracings yield time to peak inspiratory flow (Tpif) or time to peak expiratory flow (Tpef).

From these values, various ratios can be calculated that reflect respiratory drive or mechanics. For example, infants and adults with obstructive lung disease reach peak expiratory flow sooner in the expiratory cycle (have a shorter Tpef:Te ratio) than do healthy controls.

Despite the appeal of the noninvasiveness of these tests, several studies have suggested that measurements of tidal breathing variables are probably not sensitive enough to detect changes in airway function in individual patients.^2,3 They may be more useful in population studies, such as those on therapeutic interventions.

Flow-volume curve analysis

For many years, analysis of the shape of the tidal flow-volume loop has been used to detect abnormalities in the central airways of adults.⁴ As in older children and adults, obstructive processes that limit flow in the intrathoracic airways of infants may be evidenced by concavity of the expiratory flow-volume curve (Figure 2).

Fixed central airway obstructions (such as from subglottic stenosis) are identified by biphasic flattening of the flow-volume curve. The precise site of obstruction cannot be determined using this technique alone, but the noninvasive nature of the test is attractive.

For example, Filippone and associates⁵ analyzed flow-volume loops during tidal breathing in 113 children who presented with noisy breathing; these findings were compared with those from bronchoscopy.Three abnormal flow-volume patterns were described: inspiratory fluttering, expiratory limb flattening, and a concave expiratory loop.

The inspiratory fluttering pattern was associated with findings of laryngomalacia during bronchoscopy. The flattened expiratory limb with a normal inspiratory limb was associated with airway obstruction between the glottis and main bronchi, such as obstruc- tion caused by hemangiomas, stenosis, laryngeal web, and primary tracheomalacia.

Dynamic tidal mechanics

The mechanics of the lungs, including compliance and resistance, can be measured during quiet spontaneous breathing. Compliance is defined as the change in volume resulting from a change in pressure, while resistance is the amount of pressure required for a given flow rate.

The mechanics of the airways, lungs, or entire respiratory system can be measured separately. For example, by determining pressures at the mouth (airway opening) and in the esophagus (estimating pleural pressure), the airways and lung parenchyma are included but the chest wall is excluded; the resulting calculation is one of transpulmonary pressure. The mechanics measurements thus obtained represent pulmonary compliance and resistance (Figure 3).

Such determinations can be made in a sleeping or sedated infant during quiet breathing by simultaneously measuring transpulmonary pressure with an esophageal catheter and flow with a pneumotachograph, whose signal can then be digitally integrated to yield volume. Measurements of tidal lung mechanics have been used to evaluate lung growth and recovery from injury and the effects of various interventions on lung function.

Passive respiratory mechanics

These techniques involve measurement of total respiratory system mechanics during a passive exhalation.⁶ Passive respiratory mechanics do not require intraesophageal pressure measurements and can be performed in spontaneously breathing infants. However, the respiratory muscles must be completely relaxed. The techniques assume that alveolar pressure equilibrates with airway opening (mouth) pressure during occlusions; this assumption may not be valid in some disease states.

The most common way to achieve respiratory muscle relaxation is by eliciting the Hering-Breuer (inspiratory) reflex. The airway is occluded at a lung volume above functional residual capacity (FRC), such as end-inspiration. As a result, a brief apnea is induced and the muscles of respiration relax. When the occlusion is relieved, the subsequent exhalation is entirely passive, and the resulting pressure, flow, and volume changes represent the characteristics of the airways, lung parenchyma, and chest wall.

The single-breath occlusion technique involves occluding the airway at end-inspiration to invoke the Hering-Breuer reflex, and the resultant passive expiratory flow is measured and plotted against exhaled volume. This flow-volume curve can be used to calculate compliance (Figure 4).

This technique assumes that the entire lung behaves as a single compartment that empties uniformly. The time constant, which is the product of resistance (cm H₂O/L/s) and compliance (mL/cm H₂O), describes how quickly the lung empties. It is calculated as the inverse of the slope of the descending limb of the passive flow-volume curve (mL/mL/s), thus yielding units of seconds.

Longer time constants imply slower lung emptying. The compliance is calculated as the volume of the exhaled breath (extrapolated to 0 flow) divided by the mouth pressure at the beginning of the occlusion. The resistance of the respiratory system can then be calculated by dividing the time constant by compliance. Limitations of this technique include failure to invoke the Hering-Breuer reflex and violation of the single-compartment hypothesis, both of which can occur in infants with severe obstructive lung disease.

Forced expiratory flows

Detection of airflow obstruction, by physical examination or by quantitative measurement techniques, is facilitated by increasing expiratory flow rates. When performing spirometry, older children are coached to inspire to near-total lung capacity (TLC) and then to exhale rapidly and forcefully down to residual volume. The maximal flows generated indicate airway size.

Because infants and toddlers cannot usually cooperate with spirometry, other techniques have been used.⁷ The rapid thoracic compression (RTC) technique involves rapidly inflating a jacket that encircles the chest and abdomen of a sedated infant; the inflation is timed to occur at end-inspiration.⁸ Expiratory flow (and volume by integration) is measured via a face mask and pneumotachograph, and a flow-volume curve over the tidal range of breathing (partial forced expiratory flow) can be constructed (Figure 5).

Jacket pressures are increased until no further increases in expiratory flow occur. Instantaneous flow rates can be measured, the most common of which is the flow rate at the FRC point, or end-expiration. By increasing flow rates over tidal flow values, the ability to detect abnormal airway function is enhanced. The RTC method has been used serially to assess normal and abnormal airway growth and to gain understanding of airway function in a variety of disease states.

One major limitation of the RTC technique is the dependence of measured flows on the lung volume at which they are measured.⁹ Furthermore, end-expiratory lung volume in infants can vary dramatically, because infants actively maintain FRC. Instability of the FRC point limits the reproducibility of the flow measurements and may decrease the sensitivity of the technique to subtle changes in airway mechanics.

A modification of the RTC technique has been used to overcome the variability in lung volume at which flow measurements are made.^10,11 In the raised volume- RTC technique, the infant's lung is first inflated to a predetermined pressure (typically, 30 cm H₂O) (Figure 6). This results in an end-inspiratory lung volume that is close to TLC (whereas the RTC technique begins measurement close to FRC).

The resultant flow-volume curves are highly reproducible, with values reported as timed volumes (such as forced expiratory volume in a half second and forced expiratory volume in three fourths of a second) in addition to instantaneous flow rates. This technique also allows for flows to be measured over a larger portion of the vital capacity.

Several studies have suggested that the raised volume-RTC technique is more sensitive than the RTC maneuver for detecting diminished pulmonary function in infants.¹² Moreover, results from the former technique are strictly analogous to the flow-volume curves obtained in cooperative children and adults during standard spirometric testing.

Lung volumes

As in older children and adults, lung volumes in infants and young children can be measured by dilutional techniques or body plethysmography.^13,14 Theoretically, both methods can be used to measure any lung volume (from residual volume to TLC), but in practice, the lung volume measured is the resting end-expiratory lung volume (FRC).

Helium dilution involves an infant breathing a gas mixture through a face mask. This mixture is in a closed circuit with volume (V₁) containing a known concentration of helium (C₁), an inert gas that does not pass through the alveolar-capillary membrane.¹⁵ After an equilibration period, the final concentration of helium is measured in the breathing circuit, and the principle of conservation of mass (C₁ 3 V₁ = C₂ 3 V₂) is used to calculate the volume that was added to the circuit (volume in lung of the infant, V₂ = V₁ + V_lung).

Leaks in the circuit (especially at the face mask) result in overestimation of the lung volume (since the final concentration of helium is artifactually low). Also, noncommunicating portions of the lung volume (such as those caused by airway obstruction) are not measured; dilutional techniques may underestimate the true lung volume in these cases.

The calculation of plethysmographic measurements of lung volume involves application of the Boyle law: (P₁ 3 V₁) = (P₁ + DP) 3 (V₁ 2 DV), where P₁ is mouth pressure, V₁ is infant's resting lung volume, and DP and DV are the pressure and volume changes during breathing efforts against an occluded airway. For these measurements, the infant is placed within a rigid closed container. The infant breathes through a face mask connected to an airway pressure gauge and a pneumotachograph to measure flow and volume.

A shutter within the face mask can briefly occlude the infant's airway; continued respiratory efforts alternately compress and rarefy the gas within the lung. Because airflow is absent when the shutter occludes the airway, pressure measurements made at the mask (airway opening) reflect alveolar pres- sure. By relating alveolar pressure changes to the volume changes in the plethysmograph (which are equal and opposite to those in the infant's lung), the volume of gas within the lung can be calculated. Plethysmographic measurements include any gas in the thorax, such as that in lung units subtended by obstructed airways.

Clinical settings

A recent review suggested several clinical settings in which infant pulmonary function testing could be most useful (Table).¹ These include:

• The infant who presents with unexplained symptoms or signs, such as tachypnea, hypoxia, cough, and respiratory distress (for whom a definitive diagnosis is not apparent from physical examination or other initial studies).

• The infant with chronic obstructive lung disease (such as that associated with cystic fibrosis or ciliary dyskinesia) who does not respond to an adequate trial of combined corticosteroid and bronchodilator therapy.

• The infant with known respiratory disease of uncertain severity in whom there is need to justify management decisions.

Although infant pulmonary function testing techniques are available only at specialized centers, the Joint American Thoracic Society/European Respiratory Society Working Group on Infant Lung Function has been working for several years to develop better standardization of equipment and reference values. This has resulted in several publications.^{8,10,14,16,17} It is hoped that such efforts will bring infant pulmonary function testing into more widespread use.

References:

REFERENCES

1. Godfrey S, Bar-Yishay E, Avital A, Springer C. What is the role of tests of lung function in the management of infants with lung disease?

Pediatr Pulmonol.

2003;36:1-9.
2. Clarke JR, Aston H, Silverman M. Evaluation of a tidal expiratory flow index in healthy and diseased infants.

Pediatr Pulmonol.

1994;17: 285-290.
3. Aston H, Clarke J, Silverman M. Are tidal breathing indices useful in infant bronchial challenge tests?

Pediatr Pulmonol.

1994;17:225-230.
4. Miller RD, Hyatt RE. Evaluation of obstructing lesions of the trachea and larynx by flow-volume loops.

Am Rev Respir Dis.

1973;108: 475-481.
5. Filippone M, Narne S, Pettenazzo A, et al. Functional approach to infants and young children with noisy breathing: validation of pneumotachography by blinded comparison with bronchoscopy.

Am J Respir Crit Care Med.

2000;162:1795-1800.
6. Baraldi E, Filippone M. Passive respiratory mechanics to assess lung function in infants.

Monaldi Arch Chest Dis.

1994;49:83-85.
7. Morgan WJ, Geller DE, Tepper RS, Taussig LM. Partial expiratory flow-volume curves in infants and young children.

Pediatr Pulmonol.

1988;5:232-243.
8. Sly PD, Tepper R, Henschen M, et al. Tidal forced expirations. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

Eur Respir J.

2000;16:741-748.
9. Davis S, Jones M, Kisling J, et al. Effect of continuous positive airway pressure on forced expiratory flows in infants with tracheomalacia.

Am J Respir Crit Care Med.

1998;158:148-152.
10. The raised volume rapid thoracoabdominal compression technique. The Joint American Thoracic Society/European Respiratory Society Working Group on Infant Lung Function.

Am J Respir Crit Care Med.

2000;161:1760-1762.
11. Castile R, Filbrun D, Flucke R, et al. Adult-type pulmonary function tests in infants without respiratory disease.

Pediatr Pulmonol.

2000;30:215-227.
12. Ranganathan SC, Bush A, Dezateux C, et al. Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

Am J Respir Crit Care Med.

2002;166:1350-1357.
13. Morris MG, Gustafsson P, Tepper R, et al. The bias flow nitrogen washout technique for measuring the functional residual capacity in infants. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing.

Eur Respir J.

2001;17:529-536.
14. Stocks J, Godfrey S, Beardsmore C, et al. Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

Eur Respir J.

2001;17:302-312.
15. McCoy KS, Castile RG, Allen ED, et al. Functional residual capacity (FRC) measurements by plethysmography and helium dilution in normal infants.

Pediatr Pulmonol.

1995;19: 282-290.
16. Bates JH, Schmalisch G, Filbrun D, Stocks J. Tidal breath analysis for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

Eur Respir J.

2000;16:1180-1192.
17. Stocks J, Sly PD, Tepper RS, Morgan WJ, eds.

Infant Respiratory Function Testing.

New York: John Wiley & Sons; 1996.