Pediatric Pulmonology 20:135-I36 (1995)

Guest Editorial -

Infant Lung Function and Tidal Breathing Patterns

Recent studies have aroused increasing interest in the use of tidal breathing parameters for evaluating lung function in infants, following initial observations in adults made over 14 years ago by Morris and Lane.' They analyzed tidal expiratory flow patterns in adults with and without airway obstruction and reported correlations between forced expiratory volume in one second (FEV,) and sev- eral tidal breathing parameters. Some years later, one particular tidal breathing parameter, the ratio of the time to tidal peak expiratory flow to total tidal expiratory time, Tme/Te (also known as $,,&,), was studied in a cohort of young infants; a low value was shown to be a predictor for subsequent lower respiratory illness.' This was an exciting and promising observation, because the mea- surement of tidal flow, either with a face-mask or by body-surface movement detectors, is relatively noninva- sive. In contrast, established methods for measuring me- chanical properties of the lungs place great demands on both operator and infant. First, sedation is usually re- quired. This limits most studies of lung function to healthy infants or to symptom-free intervals in infants with respiratory disease. Secondly, specialized equip- ment is needed to achieve adequate sensitivity and accu- racy. In miniaturizing a flow-measuring device, a bal- ance has to be maintained between reducing the dead space of the equipment and increasing its resistance, both of which may affect breathing. A technique by which infant lung function could be assessed during tidal breath- ing, possibly in unsedated infants, would therefore repre- sent a great advance.

In this issue of Pediatric Pulmonology, Adler et al. report their observations on the relationship between one index of tidal breathing, the ratio of the time to tidal peak flow to total tidal expiratory time, TmeiTe (&fit,), and lower respiratory illness (LRI) in the first year of life. They studied lung function in a group of infants before the onset of any lower respiratory illness and subse- quently. In infants in whom measurements were made during the first 10 weeks of life, Tme/Te did not differ significantly between those who subsequently developed LRI and those who did not. In addition, the trend for respiratory system resistance (RJ to be higher in infants who developed a LRI compared with those who remained

healthy did not reach statistical significance. There was no significant relationship between the ratio Tme/Te and either forced expiratory flow at the functional residual capacity (FRC) by the sqeeze technique [using maximal flow at FRC (VmaxFRC)] or R,,, although VmaxFRC did correlate with Rrs. The authors do not indicate whether their study had sufficient power to reveal an important relationship between Tme/Te and respiratory symptoms.

In contrast to the situation in adult pulmonology, where it is generally acknowledged that the commonly used measurements of forced expiratory flow are largely dependent on intrathoracic airway caliber, there is con- troversy in infants about the validity of tests to measure airway ob~truct ion.~ What do different techniques actu- ally measure? In a nose-breather, the upper airway, in- cluding the nose, makes a significant contribution to air- way and respiratory resistance. It is likely that forced expiratory flow by the squeeze technique, either from tidal or augmented inspiration, gives the best estimate of intrathoracic airway o b s t r ~ c t i o n , ~ , ~ unaffected by minor degrees of nasal obstruction.6 Tidal breathing techniques do not measure lung mechanics, but rather the dynamic, neuromuscular response of the infant to mechanical con- straints imposed by lung disease. Even more remotely, indices of gas exchange (PO2 and PCO,) represent an overall, integrated view of cardiopulmonary function. How can we validate the different techniques for measur- ing infant lung function?

An adequate test of airway function should distinguish between healthy infants and those with lower airway dis- ease, or between infants before and after pharmacologi- cally induced airway narrowing or bronchoconstriction. Using the first model, we have attempted to assess tidal breathing parameters in infants. In a study similar to, but smaller than the Tucson cohort study,* we were not able to detect any difference in Tme/Te between healthy in- fants and those who did or did not develop LRL7 We also looked at a group of infants with clinical asthma, and again Tme/Te was no different from healthy infants of a similar age. In comparison toVjmaxFRC, Tme/Te was an insensitive index of airflow obstruction. Only in a group of infants with severe chronic lung disease of prematu- rity, most of whom were flow limited during tidal breath- ing, was the ratio Tme/Te outside the 95% CI for healthy infants. In another study, looking at tidal breathing indi- ces during histamine challenge, even when (VmaxFRC)

0 1995 Wiley-Liss, Inc.

136 Infant Lung Function

measured by the squeeze technique fell by over 40%, there was no significant change in Tme/Te.8 The expira- tory time constant fell, the mean tidal expiratory flow rate (tidal volume/expiratory time) increased, and the respira- tory rate increased.

Leaving aside physiological explanations, the most likely explanation for the insensitivity of Tme/Te to ma- jor changes in airway obstruction lies in the nature of the ratio itself. If respiratory rate increases with the degree of airway obstruction, then any shortening of Tme will be masked by a reduction in Te. This is the situation in infancy in contrast to adults and may explain why Tme/Te is so clearly associated with airway obstruction in adults, but not in infants. The fall in the breathing frequency during infancy (i.e., increase in Tme) provides most of the reason for the decrease in Tme/Te over the first few months of life.’

The use of a face-mask and pneumotachograph may induce a change in breathing pattern, due either to the additional mechanical constraints imposed, or to facial stimulation. Therefore, the opportunity to detect any subtle differences in tidal flow patterns might be lost. Stick and colleagues“) found good agreement between Tme/Te measured directly using a face-mask with pneu- motachograph and measurements obtained from body- surface movement by respiratory inductance plethysmog- raphy in a group of unsedated healthy infants. The application of a face-mask did not significantly affect Tme/Te, but the respiratory frequency tended to be slower, and another tidal breathing parameter, the ratio of inspiratory time to total respiratory time (Ti/Ttot), signif- icantly increased. Only healthy infants were included in this study. The effect of a face-mask might be greater in infants with lower airway obstruction.

In a large study, which was mainly community based, Dezateux and colleagues’ compared Tme/Te with air- way function measured by plethysmography . Despite their sample size of over 150 infants, they found only a weak, albeit significant, association between Tme/Te and end-expiratory specific airway conductance (EE SG,,) in infants aged over 3 months. ,Both were significantly re- duced in older infants with prior lower respiratory illness, compared with a similarly aged group of healthy infants. Benoist and colleagues’* looked at several different in- fant lung function techniques during methacholine chal- lenge in infants. These included tidal breathing parame- ters, VmaxFRC, and compliance and resistance of the respiratory system, measured with the passive expiratory flow-volume technique. Transcutaneous oxygen tension was measured as an indicator of the response to metha- choline challenge. Tidal peak expiratory flow (which

increased during challenge, as we found) and VmaxFRC were the most sensitive tests for airway obstruction. Tme/ Te, compliance, and resistance were less sensitive.

Perhaps the clue to the controversial place of Tme/Te in clinical measurement lies in deceptively simple mathe- matics. Ignore ratios at your peril; they often hide the truth!

REFERENCES

1. Moms MJ, Lane DJ. Tidal expiratory flow patterns in airflow obstruction. Thorax. 1981; 36:135-142.

2. Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med. 1988; 319:1112- 1117.

3. ATS-ERS statement. Respiratory mechanics in infants: physio- logic evaluation in health and disease. Am Rev Respir Dis. 1993; 147:474496.

4. Flucke R, Castile R, Filbrun D, Shani N, McCoy K. Measurement of full pressure volume curves of the respiratory system in sedated infants. Am J Respir Crit Care Med. 1994; 149:A694.

5 . Turner DJ, Sly PD, LeSouef PN. Assessment of forced expiratory volume-time parameters in detecting histamine-induced bron- choconstriction in wheezy infants. Pediatr Pulmonol. 1993; 15: 22G224.

6. Tepper RS, Steffan M. Airway responsiveness in infants: Com- parison of inhaled and nasally instilled methacholine. Pediatr Pul- monol. 1993; 16:54-58.

7. Clarke JR, Aston H, Silverman M. Evaluation of a tidal expiratory flow index in healthy and diseased infants. Pediatr Pulmonol. 1994; 17:285-290.

8. Aston H, Clarke J , Silverman M. Are tidal breathing indices useful in infant bronchial challenge tests? Pediatr Pulmonol. 1994; 17:225-230.

9. Dolfin T, Duffy P, Wilkes D, England S, Bryan H. Effects of a face mask and pneumotachograph on breathing in sleeping in- fants. Am Rev Respir Dis. 1983; 128:977-979.

10. Stick SM, Ellis E, LeSouef PN, Sly PI>. Validation of respiratory inductance plethysmography (“Respitrace”@) for the measurement of tidal breathing parameters in newborns. Pediatr Pulmonol. 1992; 14:187-191.

11. Dezateux CA, Stocks J, Dundas I, Jackson EA, Fletcher ME. The relationship between tmE& and specific airway conductance in infancy. Pediatr Pulmonol. 1994; 18:299-307.

12. Benoist MR, Brouard JJ, Rufin P, Delacourt C, Waernessyckle S, Scheinmann P. Ability of new lung function tests to assess meth- acholine-induced airway obstruction in infants. Pediatr Pulmonol. 1994; 18:308-316.

-Jane Clarke, MRCP Department of Thoracic Medicine

Royal Children’s Hospital Parkville, Melbourne, Victoria, Australia

-Michael Silverman, MD Department of Child Health

University of Leicester School of Medicine Leicester Royal Infirmary, Leicester, England