Published ahead of print on June 1, 2004, doi:10.1164/rccm.200401-132OC
© 2004 American Thoracic Society doi: 10.1164/rccm.200401-132OC
Elastic Properties of the Respiratory System in Infants with Cystic FibrosisDepartment of Pediatric Pulmonology and Critical Care, Indiana University School of Medicine, and James Whitcomb Riley Hospital for Children, Indianapolis, Indiana Correspondence and requests for reprints should be addressed to Robert S. Tepper, M.D., Ph.D., Department of Pediatrics, Indiana University School of Medicine, James Whitcomb Riley Hospital for Children, 702 Barnhill Drive, Room 4270, Indianapolis, IN 46202-5225. E-mail: rtepper{at}iupui.edu
Respiratory system compliance (Crs) in infants with cystic fibrosis (CF) has been reported as decreased or not different compared with healthy control subjects; however, the reported measurements of Crs were "quasi-static" or by the single-breath occlusion technique, with all measurements limited to tidal lung volume, as well as using inspiratory rather than expiratory pressures. We compared the passive elastic properties of the respiratory system of sleeping infants with CF (n = 10) and healthy control subjects (n = 34) by measuring static deflation pressure–volume (PV) curves from a lung volume at 30 cm H2O (V30) to FRC. There was no significant difference between the groups for Crs, which was measured as the slope between airway relaxation pressures of 5 and 15 cm H2O, the linear portion of the deflation PV curve. In addition, when PV curves were normalized to V30, there were no differences between the infants with CF and healthy control subjects in the fractional volumes at any airway pressure. The infants with CF had significantly lower forced expiratory flows; however, lower flows did not correlate with fractional volumes measured from the PV curve. Our findings indicate that infants with CF have normal elastic properties of the respiratory system.
Key Words: compliance • pressure–volume curves Previous measurements of the compliance of the respiratory system (Crs) of infants with cystic fibrosis (CF) have yielded conflicting results as to whether there are abnormalities in the elastic properties of the respiratory system of patients with CF early in life. Cystic fibrosis is primarily an airway disease secondary to airway infection and inflammation; however, older children and adults with CF can demonstrate decreased pulmonary elastic recoil, which can contribute to airway obstruction (1, 2). The earliest studies of infants with CF reported decreased dynamic compliance, which could result from peripheral airway obstruction and maldistribution of ventilation (3). We have previously reported decreased "quasi-static" compliance of the respiratory system in infants with CF when assessed by the weighted spirometer technique (4). However, using the single-breath occlusion technique, Mohon and coworkers reported no difference in Crs between asymptomatic infants with CF and healthy control subjects (5). Both of these later techniques may underestimate compliance as the measurements are limited to the lung volume range of tidal breathing, where airway closure may be present at this lung volume, particularly as neither of these two methods assesses the deflation pressure–volume characteristics of the respiratory system. Therefore, it remains unclear whether the elastic properties of the respiratory system of infants with CF differ from those of healthy infants. We have described a technique to obtain passive deflation pressure–volume curves from near total lung capacity (TLC) to FRC in healthy sleeping infants (4). Several inflations to near TLC elicit a respiratory pause, which permits multiple brief airway occlusions and measurement of relaxation pressures as the respiratory system passively deflates from near TLC to FRC. The purpose of the current study was to determine whether the static deflation pressure–volume characteristics of the respiratory system differ between infants with cystic fibrosis and healthy control infants.
Subjects We evaluated 10 infants with CF (41–97 weeks), who had no acute pulmonary exacerbation or respiratory symptoms for at least 3 weeks before testing. The 34 healthy control infants (0.9–101.4 weeks) were part of a larger group previously reported (4). The Indiana University (Indianapolis, IN) Institutional Review Board approved the study and parental consent was obtained.
Equipment and Measurements
Passive Deflation Pressure–Volume Curve
Forced Expiratory Flows Forced expiratory maneuvers from elevated lung volumes were performed by the rapid thoracic compression technique as previously described (6). The best flow–volume curve was selected as that curve with the highest product of FVC and the forced expiratory flow between 25 and 75% expired volume (FEF25–75). The FVC was calculated as the expired volume between V30 and residual volume. Forced expiratory flows were measured at 50 and 75% expired volume (FEF50 and FEF75, respectively), as was the FEF25–75. Each pulmonary function parameter was expressed as a Z score, using the regression equation and variance derived from a reference population evaluated in our laboratory (6).
Analysis
There were no significant differences for age, length, weight, or sex between the two groups; however, the infants with CF tended to be older than the healthy control subjects (Table 1). The CF group had significantly lower percentiles of weight and length for age (13 versus 43 and 10 versus 36, respectively; p < 0.01).
For both groups of infants there was a significant relationship between V30E and body length: the longer the infant, the larger the V30E; however, there was no significant difference in V30E between the two groups of infants, even when adjusted for length (Figure 2).
All the pressure–volume curves were linear between 5 and 15 cm H2O (r2 > 0.99). The coefficient of variation for repeat measurements of Crs was 6% for both the CF and healthy control groups. For both groups of infants there was a significant relationship between Crs and V30E: the larger the lung volume, the greater the Crs value (Figure 3). After adjusting for V30E by analysis of variance, infants with CF had lower values for Crs compared with healthy control subjects (p < 0.01). However, as the CF group tended to be older, the analysis was repeated with the group of healthy control subjects limited to those infants greater than 40 weeks of age; this cutoff resulted in there no longer being a tendency toward a difference in age for the two groups (p > 0.7) and Crs was no longer significantly different for the two groups (p > 0.5).
The quadratic equation produced a good fit for all the pressure–volume curves (r2  0.99) and the fraction of V30E was calculated for pressures of 2, 5, 10, 15, 20, 25, and 30 cm H2O. The group means for the fraction of V30E at each of these pressures were not significantly different for the CF and healthy control groups (Figure 4).
Forced expiratory maneuvers demonstrated that there was no significant difference in FVC (Z scores) for the CF and healthy control groups; however, infants with CF had significantly lower forced expiratory flows (Table 2). There were no significant correlations between the Z scores for forced expiratory flows (FEF75 and FEF50) and fraction of V30E at airway pressures of 2 or 4 cm H2O; those infants with higher fractional volumes did not have lower forced flows.
By using several inflations to an airway pressure of 30 cm H2O, we obtained deflation pressure–volume curves for infants with CF over an extended range of lung volumes, from near TLC to FRC. Compared with previous studies, in which pressure–volume measurements were limited to the range of tidal lung volume, the current methodology has the advantage of standardizing lung volume history, opening airways that may close during tidal breathing in the supine position, as well as obtaining measurements during deflation over an extended range of lung volumes. We found that our group of infants with CF demonstrated airway obstruction; however, the deflation pressure–volume curves of the respiratory system for the CF group did not differ from those obtained from healthy control subjects. This finding is consistent with the concept that the early pathophysiology of CF is limited to the airways and that the decrease in forced expiratory flow is not related to an alteration in the elastic properties of the respiratory system. Compliance of the respiratory system was measured over the linear portion of the pressure–volume curve between 5 and 15 cm H2O. Crs for the infants with CF increased with increasing lung volume, similar to our previous findings in the healthy control infants (4). The reference lung volume used was the passive exhaled volume measured just before the multiple occlusion deflation pressure–volume curves. We chose this exhaled volume as we have found that infants have a brief apnea after this passive exhalation; therefore, this volume is the complete exhalation volume between 30 and 0 cm H2O. The increased time required for exhalation during the multiple occlusion maneuver results in a few infants inspiring at an airway pressure within the tidal volume range, between 5 and 0 cm H2O, before reaching FRC. Therefore, the total exhaled volume during the deflation pressure–volume maneuver may be less than the complete exhalation volume to FRC. When adjusted for lung volume, the group of infants with CF had a small but significantly lower Crs than did the group of healthy control infants. However, when the younger healthy control infants were removed from the analysis, so that the groups were matched for age, there was no significant difference between the two groups. The difference in the results of the two analyses reflects the greater specific compliance of the respiratory system of younger compared with older healthy control infants (4, 7). When evaluating malnourished infants, such as infants with CF, matching for body size, but not age, may lead to a false interpretation, particularly when there are maturational changes in respiratory physiology. In addition to calculating the compliance of the respiratory system from the linear portion of the pressure–volume curve, we compared the full deflation pressure–volume curves, which included the nonlinear portions. The multiple occlusions during the deflation pressure–volume curve occur at fixed time intervals and not specific airway pressures. Therefore, the nonlinear equation, which provided a good fit to the data, was used to generate a curve with volume normalized to V30E at specific airway pressures. We found no differences in the elastic properties of the respiratory system of the CF and healthy control infants at any of the airway pressures. In summary, we found that healthy infants with CF have decreased forced expiratory flows and normal elastic properties of the respiratory system. This finding is consistent with the concept that the early pathophysiology of CF is limited to the airways and that the decrease in forced expiratory flow is not related to an alteration in the elastic properties of the respiratory system.
Supported by NIH grant HL-54062. Conflict of Interest Statement: R.S.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; A.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; T.W.-N. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; J.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Received in original form January 30, 2004; accepted in final form May 31, 2004
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