Predicting the outcome of respiratory disease in wheezing infants using tidal flow-volume loop shape.

INTRODUCTION AND OBJECTIVES: Wheezing (RW) infants with a positive asthma predictive index (API+) have a lower lung function as measured by forced expiratory techniques. Tidal flow-volume loops (TFVL) are easy to perform in infants, and sedation is not necessary. MATERIALS AND METHODS: A total of 216 wheezing infants were successfully measured, and 183 of them were followed for over a year. TFVL loops were classified into one of three categories depending of their geometric shape (symmetric, convex, and concave). Respiratory rate (Rr), presence of API+, and the number of exacerbations during the following year were also recorded. RESULTS: Children with concave loops had more exacerbations in the following year (OR = 6.8 [IC95% 3.33;13.91]). Infants API + were also significantly more related to concave loops (OR = 10.02 [IC 95% 4.53; 22.15]). Rr was higher in infants with concave loops (44+/-15.5 vs. 36.6 +/-12.6; p < 0.01). CONCLUSION: Infants with a concave TFVL have a higher probability of experiencing exacerbations in the following year, and are at a higher risk of suffering asthma.

Caffeine potentiates airway responsiveness in the neonatal lamb.

In contrast to its effect on airway smooth muscle in the adult, in vitro studies have shown that caffeine significantly increases active tension in airway smooth muscle in the neonatal lamb. To determine if caffeine has a physiological effect on airway function during early development, we studied the effect of caffeine on acetylcholine-induced bronchoconstriction in two groups of neonatal lambs. The animals were anesthetized, paralyzed, and maintained normoxic and normocapnic with mechanical ventilation. Pulmonary mechanics were evaluated as indices of airway tone, and functional residual capacity was used as an index of lung volume; heart rate and mean arterial pressure were used to assess cardiovascular status. Acetylcholine-induced bronchoconstriction was evaluated as percentage changes of airway conductance and lung compliance from baseline, before and 1 hour after administration of normal saline or caffeine, and it was further analyzed with respect to the dose that produced a 20% change in those values (PD20). There were no significant alterations in baseline lung mechanics, lung volume, or mean arterial pressure following saline or caffeine infusion. However, caffeine produced a left shift in the acetylcholine dose-response curve for conductance and compliance and a significant decrease (-52%; P less than 0.001) in PD20 for conductance. There were no significant alterations in any parameter following saline administration. Since caffeine is used commonly for the treatment of apnea of prematurity, it is noteworthy that caffeine increases airway reactivity at clinically relevant doses. These findings raise important issues regarding the use of caffeine for the treatment of apnea of prematurity.

Effect of altering smooth muscle tone on maximal expiratory flows in patients with tracheomalacia.

We obtained maximal partial expiratory flow-volume (PEFV) curves using the rapid compression technique in three infants with intrathoracic tracheomalacia. Maximum flows were quantitated at functional residual capacity (VmaxFRC). Studies were performed at baseline, after inhalation of methacholine (MCh) and after inhalation of albuterol. At baseline, all three patients had significantly lower than normal VmaxFRC values, and two patients displayed expiratory flow limitation during tidal breathing. VmaxFRC improved significantly after MCh administration, but fell back toward or below baseline after albuterol. Additionally, the ratio of forced to tidal flows at mid-tidal volume (Vmid(forced/tidal), a reflection of expiratory flow reserve, increased after MCh administration and decreased after albuterol. Two patients also received oral bethanechol: 2.9 mg/M2, q 8 hr for 10 days, after which PEFV curves were repeated. Both Vmax FRC and Vmid(forced/tidal) were increased over baseline after bethanechol administration, but decreased after albuterol. These results suggest that in patients with abnormally collapsible tracheae, stimulation of tracheal smooth muscle can improve airway stability, thereby increasing forced expiratory flows. Additionally, relaxation of airway smooth muscle by bronchodilators can have the opposite effect and exacerbate obstruction.

Interaction between chest wall motion and lung mechanics in normal infants and infants with bronchopulmonary dysplasia.

Asynchronous or paradoxic motion between the rib cage and abdomen may be seen in infants with lung disease. We have recently shown that after bronchodilator administration, the degree of asynchrony decreases proportionately to the improvement in lung mechanics. However, whether such thoraco-abdominal asynchrony (TAA) is a useful indicator of lung function in a cross-sectional population, i.e., whether asynchrony correlates with baseline lung mechanics, is unknown. Therefore, we quantitated the degree of TAA using respiratory inductive plethysmography during quiet sleep in ten infants with bronchopulmonary dysplasia (BPD) and six weight-matched control infants. We displayed abdominal wall (AB) and rib cage (RC) motion on an X-Y recorder, and from the tidal breathing loop we calculated a phase angle phi, between 0 degrees and 180 degrees as an index of asynchrony (synchronous RC/AB motion = 0 degrees, paradox = 180 degrees). Lung resistance (RL) and compliance/kg (CL/kg) were calculated from esophageal and mouth pressure, tidal volume, and tidal flow. As expected, BPD infants had abnormally high RL, and low CL/kg when compared to controls. All infants with BPD displayed marked thoraco-abdominal asynchrony (phi = 102 +/- 16 degrees, mean +/- SEM; range 35 degrees-160 degrees) with controls displayed synchronous chest wall motion (phi = 8 +/- 3 degrees, range 0 degrees-15 degrees) (P less than 0.001). The degree of TAA was significantly correlated with RL (r = 0.773, P less than 0.001) and inversely correlated with CL/kg (r = -0.67, P less than 0.01). We conclude that in infants of similar weight, TAA may be used as a cross-sectional index reflecting both resistive and elastic properties of the lungs.

Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants.

The ability to maintain effective tidal volume and minute ventilation during resistive loaded breathing depends on both adequate central neural respiratory output response and respiratory system mechanical properties such as respiratory muscle strength and chest wall stability. We hypothesized that chest wall instability limits the ability of the preterm (PT) infant to respond to inspiratory resistive loading (IRL) compared with full-term (FT) infants. To test this hypothesis, we subjected eight FT and 10 PT infants to IRL with loads of 1.3, 2, and 6 times intrinsic lung resistance and measured steady state tidal volume (VT), minute ventilation (VE), and chest wall motion. Thoracoabdominal asynchrony was measured by respiratory inductive plethysmography and quantitated by measuring the phase angle, theta, between rib cage and abdominal motion (0 degrees = synchronous motion, 180 degrees = paradoxic motion). At baseline, VT/kg (mL/kg, mean +/- SEM) was similar between PT (7.0 +/- 0.7) and FT (7.5 +/- 0.5) infants. VE/kg (mL/min/kg) was greater in PT (545 +/- 50) than in FT (385 +/- 33) infants (p < 0.05) as a result of increased respiratory frequency in the former. PT infants demonstrated significantly greater chest wall asynchrony (theta = 38 +/- 9 degrees) than FT infants (theta = 9 +/- 3 degrees) (p < 0.01). With the highest resistive loads, VT decreased significantly in the PT but not the FT infants. Furthermore, during IRL, VE decreased to 417 +/- 50 mL/min/kg (p < 0.05) and theta increased to 56 +/- 7 (p < 0.05) in the PT infants, whereas no significant change in either value was observed in the FT group.(ABSTRACT TRUNCATED AT 250 WORDS)