Surgery – Diagnostic testing – Respiratory
Reexamination Certificate
2000-02-17
2001-10-23
Nasser, Robert L. (Department: 3736)
Surgery
Diagnostic testing
Respiratory
C600S532000
Reexamination Certificate
active
06306099
ABSTRACT:
BACKGROUND OF THE INVENTION
Objective assessment of lung function has provided valuable insights into the normal process of growth and development of infant lungs and airways. It is also an important component in the diagnosis and management of respiratory diseases and disorders, and is essential to our understanding of their acute or chronic effects and eventually our ability to prevent or minimize these effects (American Thoracic Society/European Respiratory Society. Respiratory mechanics in infants: physiological evaluation in health and disease.
Am Rev Respir Dis
1993; 147: 474-96.).
The functional residual capacity (FRC), i.e., the volume of air in the lungs and airways at end-tidal expiration, is the only lung volume that is routinely measured in infants. (American Thoracic Society/European Respiratory Society. Respiratory mechanics in infants: physiological evaluation in health and disease.
Am Rev Respir Dis
1993; 147: 474-96; Gaultier C. Lung volume in neonates and infants.
Eur Respir J
1989; 2(Suppl 4: 130s-4s)). In infants, FRC is usually dynamically determined, in that young infants inspire before expiration ends passively. (LeSouëf PN, England S J, Bryan A C. Passive respiratory mechanics in newborns and children.
Am Rev Respir Dis
1984; 129, 552-56.). Therefore, FRC is an unreliable volume landmark known to shift with many dynamic events, including the airway caliber (Maxwell D L, Prendiville A, Rose A, et al. Lung Volume changes during histamine-induced bronchoconstriction in recurrently wheezy infants.
Pediatr Pulmonol
1988; 5,145-151), sleep state (Stark A R, Cohlan B A, Waggener T B, et al. Regulation of end-expiratory lung volume during sleep in premature infants.
J Appl Physiol
1987; 62; 1117-23; Beardsmore C S, MacFayden U M, Moosavi S S, et al. Measurement of lung volume during active and quiet asleep in infants.
Pediatr Pulmonol
1989; 7:71-77.) and the addition of dead space (Stick S M, Arnott J, Turner D J, et al. Bronchial responsiveness and lung function in recurrently wheezy infants.
Am Rev Respir Dis
1991; 144, 1012-15). Previous measurements of other lung volumes such as the residual volume (RV); i.e., the volume of air remaining in the lung at the end of a forced expiration, and total lung capacity (TLC) either required invasive techniques or had an unacceptable reproducibility.
SUMMARY OF THE INVENTION
We have therefore developed a new technique to measure RV noninvasively by nitrogen washout in infants. It should be noted that although the preferred embodiment of the invention employs nitrogen, the invention is not so limited, and other inert gases, such as helium, are acceptable in the practice of the invention.
We have investigated the methodological aspects of our new technique and applied it to a group of infants who have cystic fibrosis (CF). The basic underlying concept of this investigation was the observation of an inhibition of the infant's respiratory drive when several rapid lung inflations preceded the performance of rapid thoracoabdominal compression (RTC) from a raised lung volume (RVRTC). Feher A, Castile R, Kisling J, et al. Flow limitation in normal infants: a new method for expiratory maneuvers from raised volume.
J Appl Physiol
1996; 80 (6), 2019-25. This brief inhibition not only allowed the forced expiration by RTC to proceed, uninhibited by the infant's inspiratory effort, to residual volume, but also to be followed by a respiratory pause before the resumption of spontaneous respiration. Our working hypothesis was that by measuring the volume of nitrogen expired after end-forced expiratory switching of the inspired gas from room air to 100% oxygen while thoracoabdominal compression was maintained during the post-expiratory pause, RV could be reliably estimated from the volume of expired nitrogen. In CF lung disease, the small airways are affected at an early stage, resulting in obstructive airflow limitations with consequent overinflation. (Davis P B. Pathophysiology of lung disease in cystic fibrosis. In: Davis P B, ed.
Cystic Fibrosis
. New York: Marcel Dekker, Inc, 1993: 193-218.). Hence, we think that measurement of RV could be more useful than FRC in investigating early air trapping due to small airway obstruction in CF. Therefore, the second aim of this study was to ascertain whether, in each infant, RV measurements would be reproducible and consistently lower than FRC.
We used a commercial system (PPU) designed to measure the functional residual capacity (FRC) {the volume of air remaining in the lung at the end of a tidal expiration} by the nitrogen washout technique. Using a custom-made system to induce a forced expiration, we used the PPU to measure the residual lung volume (RV) {the volume of air remaining in the lung at the end of a forced expiration}. FRC, the only lung volume to be routinely measured in infants, is an unreliable volume landmark. The present invention is the first noninvasive and reproducible measurement of RV that can be routinely used in infants.
Inherent to the new technique is the capability of measuring, noninvasively, and for the first time, the total lung capacity (TLC
30
) at a raised lung volume (V
30
) to an airway opening pressure (P
ao
) of 30 cm H
2
O. We measured it in three different ways. A computer-controlled system can be easily designed to perform automatically all these measurements.
RV has either been measured invasively or with an unacceptable reproducibility (ATSIERS, 1993). Commercially available infant pulmonary function equipment is not designed to measure RV. I have two separate infant systems that were used in unison to perform the measurement. RV measurements were very reproducible, mostly within 5%, and in five patients, 2%. In each infant, measurements of RV and FRC were reproducible and did not overlap even in the presence of a significant airway obstruction or tachypnea. I anticipate RV measurements will be routinely done in every infant pulmonary lab in the world. The measurements of RV, TLC
30
and FRC will provide the most comprehensive assessment of lung volumes in infants, in health and disease, from birth until three years. I think lung growth can be more reliably assessed by RV and TLC
30
than FRC alone. The ratio of RV/TLC
30
is important in studying air trapping in the lung, as is the case in older children and adults, in diseases such as bronchopulmonary dysplasia in infants born prematurely and cystic fibrosis.
TLC
30
has been measured invasively by tracer gas (Thorsteinsson et al., 1994) and nitrogen (Hammer et al., 1998) washout in intubated infants in the intensive care unit. We measured it noninvasively in three ways:
1. Raising the lung volume (V
30
) to an airway opening pressure (P
ao
) of 30 cm H
2
O then allowing expiration to proceed passively. The squeeze jacket for rapid thoracoabdominal compression (RTC) is triggered before the end of the passive expiration to induce a forced expiration down to residual volume (RV). Flow is integrated to produce volume, the vital capacity (from V
30
down to RV). By measuring the volume of nitrogen expired after end-forced expiratory switching of the inspired gas from room air to 100% oxygen while thoracoabdominal compression was maintained during the post-expiratory pause, RV is estimated. TLC
30
represents the sum of RV and the expired volume (vital capacity) from V
30
down to RV. By analyzing the airway pressure signal, the exact switching time is determined as well as a characteristic negative deflection caused by the outward springing of the compressed chest, occurring synchronously with jacket deflation.
2. By raising the lung volume to P
ao
of 30 cm H
2
O, and measuring the volume of nitrogen expired after switching the infant at V
30
from room air into 100% oxygen, TLC
30
was estimated.
3. Measuring the forced vital capacity (FVC) from V
30
. Then, measuring RV separately as described in paragraph 1 above. TLC
30
equals FVC plus RV (as described in the following detailed description).
After extensive in vitro experiments, using a calibrated
Board of Trustees of the University of Arkansas
Cox, Jr. Ray F.
Nasser Robert L.
Natnithithadha Navin
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