Mechanical dissociation of bronchi from parenchyma in the immature piglet lung.

Previous studies of isolated piglet lungs suggested that local distending forces around bronchi might be relatively weak before postnatal growth and maturation. The present study used tantalum bronchograms to compare pressure-diameter relationships of bronchi in situ and after excision from the parenchyma in immature (3- to 7-day-old) and mature (3-mo-old) piglets. The mature group reproduced behavior that is well established in mature lungs from other species; i.e., bronchial diameters maintained a constant relationship to the parenchyma as the lungs were deflated from maximum to minimum volume. In sharp contrast, diameters failed to change until the immature lungs were deflated to <5 cmH(2)O transpulmonary pressure. Total percent change in bronchial diameter was then only 24% in the immature lungs compared with 47% in the mature lungs (P < 0.002). Total elastances of mature generation 3-8 bronchi did not change when they were excised from the parenchyma. However, in the same generations of immature bronchi, total elastances were lower after than before (1.06 vs. 1.60 cmH(2)O/%, P < 0.05) excision from the parenchyma. Elastances of the excised immature and mature bronchi were then the same (1.06 vs. 1.03 cmH(2)O/%, not significant). Because elastic moduli of the lung parenchyma are also similar in the two age groups, it was concluded that local features of airway-parenchyma coupling limited the generation of local parenchymal recoil around bronchi in the immature lungs.

The relationship between oxygen saturation and the clinical assessment of acutely wheezing infants and children.

The objective of this study was to determine the relationship between oxygen saturation (Sao2) and traditional clinical assessment measures in infants and young children presenting as outpatients with acute wheezing. To accomplish this, Sao2 before and after medication was compared in a post hoc analysis with the clinical response to treatment (respiratory rate and a standardized index of respiratory distress) in children who participated in a randomized, placebo controlled medication trial. The study was done in a pediatric emergency department and outpatient clinic, and the participants were 74, full-term previously well infants and young children, aged 1 to 36 months (mean age 16.1 months), presenting with acute wheezing and participating in the randomized trial. The results showed that Sao2 was found to be inversely correlated with both respiratory rate (r = -0.29, P < or = 0.05) and an index of respiratory distress (r = -0.36, P < or = 0.01) prior to medication but not afterward. There was no significant difference in Sao2 when infants, who had a clinical response to treatment based on a priori criteria, were compared to nonresponders (mean difference per patient: responders = 0.86% vs nonresponders = 0.79%, P = 0.51). This was due to a large amount of individual variability in postmedication Sao2 in both groups. We conclude that, before therapy, there are only weak correlations between SaO2 and both respiratory rate and an index of respiratory distress in acutely wheezing infants and children. After therapy, young children can appear clinically improved but measured oxygen saturation may be variable and not correlated with traditional clinical assessment measures.

Postnatal growth of lung parenchyma in the piglet: morphometry correlated with mechanics.

BACKGROUND: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422-1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. METHODS: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6-12 hours, n = 3), at 3-5 days (n = 6), 25-30 days (n = 5), and 80-85 days (n = 3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. RESULTS: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3-5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. CONCLUSIONS: 1) A relative stiffness to shape and volume change in freshly newborn piglet lungs is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil.

Follicular bronchitis in the pediatric population.

Five patients in a pediatric population were identified with idiopathic follicular bronchitis (IFB) by open lung biopsy and their case records were reviewed. All were tachypneic and had a chronic cough by 6 weeks of age. The physical examination was characterized by diffuse fine crackles in four patients and by coarse rhonchi in one. The chest radiographs in all demonstrated a diffuse interstitial pattern. None had a collagen vascular or an autoimmune disease demonstrable. Response to corticosteroid therapy was minimal. Associated or coincidental esophageal reflux was treated surgically in two. No viral or bacterial agents were isolated in the sputum or the biopsy specimens. Patients have been followed up for 2 to 15 years; the conditions of all patients improved at about 2 to 4 years of age. The older patients have residual mild obstructive lung disease. To our knowledge, this is the first reported series of IFB in the pediatric population.

Maturation of interdependence between extra-alveolar arteries and lung parenchyma in piglets.

Mechanical interdependence between intrapulmonary structures and parenchyma has not been studied previously in immature postnatal lungs. To study these interactions, lung elastic moduli were measured by pressure-volume and punch indentation studies in lobes excised from 3-day-old (n = 6), 1-month-old (n = 6), and 3-month-old (n = 7) piglets. After extra-alveolar arteries were filled with a radiopaque fluid silicone compound, transpulmonary pressure and arterial pressure were varied independently as the lobar vein was occluded. Arterial diameters and lengths were measured from radiographs. Behavior of 3-month-old lungs was consistent with previous studies of adult lungs, but results were unique in 3-day-old lungs. That is, during stepwise deflation of the immature lungs 1) intravascular pressures fell when arteries were occluded experimentally, 2) arteries increased their diameters when kept at a constant intravascular pressure, and 3) arterial lengths decreased by less than 3%. Behavior of 1-month-old lungs was intermediate. A previous continuum mechanics analysis of pressure-diameter behavior was modified to account for compression by alveolar pressure as vascular diameters increase. It was concluded that 1) radial and axial dimensions of extra-alveolar arteries are virtually independent of parenchymal expansion in newborn piglet lungs and 2) periarterial interstitial pressures increase as these lungs are inflated. Our interpretation of these findings is that a mechanical association of the arteries to the parenchyma occurs gradually with postnatal maturation.

The efficacy of nebulized metaproterenol in wheezing infants and young children.

The benefit of beta-adrenergic agonists in the treatment of acutely wheezing infants and young children has not been well documented in the outpatient setting. To determine the efficacy of nebulized metaproterenol sulfate, 74 children aged 36 months or younger with acute wheezing participated in a double-masked, randomized, placebo-controlled clinical trial. Children received nebulized metaproterenol, either as an initial treatment or after a control treatment with normal saline solution. At baseline and 20 minutes after each treatment, an assessment was made that included measurements of heart rate, respiratory rate, oxygen saturation, and clinical variables related to respiratory compromise with the use of a standardized respiratory distress index (RDI). Children who received saline solution as initial therapy had no significant differences from baseline in any of the assessment measures. After metaproterenol therapy, children demonstrated an increase in heart rate ([mean +/- SD] 147 +/- 14 beats per minute vs 153 +/- 16 beats per minute), a decrease in respirations (50/min +/- 5/min vs 45/min +/- 7/min), improvement (lower scores) on the RDI (24 +/- 4 vs 15 +/- 2), and an increase in oxygen saturation (94.1% +/- 2.7% vs 95.3% +/- 3.0%). Patients aged 12 months or younger (n = 37) benefited from metaproterenol treatment (improvement in respiratory rate and RDI) but not to the same degree as children aged 24 months or older (n = 23) (improvement in respiratory rate, RDI, and oxygen saturation). Compared with assessments made before metaproterenol treatment, patients with respiratory syncytial virus infection (n = 21) had improvement in respirations (52/min +/- 7/min vs 45/min +/- 6/min) and RDI scores (22 +/- 4 vs 14 +/- 3). Based on a priori criteria (reduction in a premedication respiratory rate of 20% and an RDI score of 50%), responders to metaproterenol therapy included 45% of the entire sample and, respectively, 40% of those aged 12 months or younger, 52% of those aged 24 months or older, and 48% of patients who tested positive for respiratory syncytial virus. Although there appears to be an age-dependent degree of response, metaproterenol is effective in relieving the respiratory distress of young acutely wheezing children, including those with documented respiratory syncytial virus bronchiolitis.

Ventilatory response to exercise after intracardiac repair of tetralogy of Fallot.

Previous radionuclide studies have shown residual maldistribution of lung perfusion after intracardiac repair of Tetralogy of Fallot (TF). Maldistribution of perfusion may also be detectable by measurements of gas exchange during exercise. Thus, we used exercise to test for maldistribution of perfusion in 13 children (8 to 18 yr of age) who were clinically well (New York Heart Association Class 1) 7 to 14 yr after repair of TF. Sixteen children, matched to the study group by age, size, and sex, served as control subjects. Peak oxygen consumption during progressive exercise on a cycle ergometer was 28.7 +/- 6.6 (SD) ml/kg/min for the study group compared with 35.7 +/- 6.9 for the control subjects (p less than 0.05). During steady-state exercise at a VCO2 of 0.6 L/min, ventilation (VE) and the ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) were high (VE/VCO2 = 35.9 +/- 4.4 versus 32.0 +/- 3.5, p less than 0.05), whereas mixed expired and end-tidal CO2 concentrations were low (PETCO2 = 34.0 +/- 2.4 versus 39.2 +/- 3.0 mm Hg, p less than 0.001). Indices of pulmonary function were normal; FVC values were 96 +/- 17% and FEV, values were 96 +/- 16% of predicted values. Therefore, children who are clinically well may exhibit gas exchange abnormalities compatible with mild maldistribution of lung perfusion 7 to 14 yr after repair of TF.

Elastic moduli of lungs during postnatal development in the piglet.

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.

Cardiorespiratory response to exercise after the Fontan procedure for tricuspid atresia.

Noninvasive exercise testing was used to assess gas exchange in 13 patients age 6-25 yr who had undergone Fontan procedures for tricuspid atresia, five of whom had preexisting Glenn shunts. The results were compared to 28 age- and sex-matched controls. Oxygen saturation was measured by ear oximetry at rest and after exercise. Ventilation, oxygen consumption (VO2), carbon dioxide production (VCO2), and heart rate were measured during progressive exercise. The ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2), mixed expired pCO2 (PECO2) end-tidal pCO2 (PETCO2), and dead space to tidal volume ratio (VD/VT) were determined during steady state exercise on a cycle ergometer. Heart rate was higher for VO2 by 15% (p less than 0.02) and ventilation was higher for both VO2 (by 37%, p less than 0.001) and VCO2 (by 27%, p less than 0.002) in the patients than the controls. Mean VE/VO2 was 35.4 +/- 7.8 (SD) compared to 25.8 +/- 3.1 (p less than 0.001) and mean VE/VCO2 was 41.7 +/- 9.0 compared to 31.6 +/- 4.3 (p less than 0.001). Mean PECO2 was 21.4 +/- 4.4 torr with controls at 27.9 +/- 3.8 (p less than 0.001) and mean PETCO2 was 33.0 +/- 5.3 torr compared to 40.0 +/- 3.3 (p less than 0.001). The patients had a mean oxygen saturation of 92 +/- 5% at rest and abnormal saturation after exercise (87 +/- 9, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral diaphragmatic paralysis inhibits postnatal lung growth in the piglet.

To test the hypothesis that regional growth of lung parenchyma depends on regional distending pressure, left cervical phrenectomy was done in ten 2-month-old piglets. The unilateral diaphragmatic paralysis reduced mean transpulmonary pressure in the left hemithorax from 5.5 +/- 1.0 (means +/- SD) to 2.5 +/- 1.2 cm H2O (p less than 0.01, n = 5). When five of the piglets were killed 48 h later, wet lung weight, total protein content, and nucleic acid content did not differ from values in the five sham operated controls. The five remaining phrenectomized piglets were compared to their five sham-operated controls 7 days after surgery. Wet weight of the left lung was reduced by 29% (p less than 0.01) and DNA content was reduced by 18% (p less than 0.05). Wet weight of the right lung, contralateral to the paralyzed hemidiaphragm, was reduced by 11% (p less than 0.05). At this time, body weight, bilateral transpulmonary pressure, and ratios of total protein/DNA and RNA/DNA in lung tissue did not differ from the sham-operated controls. These results suggest that regional growth of lung parenchyma by cell proliferation adjusted to changes in regional transpulmonary pressure caused by the unilateral phrenectomy.

Cardiorespiratory response to exercise in patients with thalassemia major.

The cardiorespiratory response to exercise was examined in 13 patients, 12 to 22 yr of age, who were in stable condition while receiving regular transfusions for thalassemia major. Before transfusion (Hgb, 10.8 g/dl), the patients had reduced peak oxygen consumption for body weight (by 25%, p less than 0.002) in comparison with 20 age- and sex-matched control subjects (Hgb, 13.8 g/dl). The ventilatory equivalent for carbon dioxide was significantly reduced at all work rates, and end-tidal PCO2 was abnormally high (46.3 versus 40.7 mm Hg, p less than 0.001), but ventilatory reserve, as estimated from pulmonary function tests, was normal. Both heart rate and cardiac output (as estimated by the indirect Fick method) were abnormally high during exercise; at an oxygen consumption of 19 ml/min/kg, heart rate was 13% higher (p less than 0.01) and, at 16 ml/min/kg, cardiac output was 28% higher (p less than 0.001) in the patients than in the control subjects. Nine patients were retested 3 to 8 days after transfusion (Hgb, 13.0 g/dl, p50, 26.4 mm Hg). Neither ventilatory nor circulatory abnormalities improved significantly. In patients 12 to 22 yr of age in stable condition with thalassemia major, we conclude: cardiac output, estimated by the CO2 rebreathing method, is high and arteriovenous O2 extraction is low during exercise; the high cardiac output during exercise is associated with hypoventilation; the high cardiac output is independent of short-term changes in hemoglobin concentration associated with transfusion.

Update: signs and symptoms of pulmonary disease in children.

A few pulmonary diseases that occur only during childhood are associated with clinical manifestations rarely seen in adults. Most of the manifestations of pulmonary disease unique to children are probably explained by growth and development rather than by unique features of the diseases themselves. Therefore this article is oriented more toward growth and development than toward disease. This discussion is limited to relatively new knowledge, much of it a product of applied technology. The intent is to help those interested in pediatric lung disease to develop new clinical perceptions or to "calibrate" some they already have.

Pulmonary follow-up of moderately low birth weight infants with and without respiratory distress syndrome.

Pulmonary function was measured in 18 children aged 6 to 9 years who had been born prematurely (mean birth weight 1760 +/- 555 g) and who had each received greater than 100 hours (mean 177 +/- 74 hours) of mechanical ventilation for respiratory distress syndrome (RDS). We used as controls 26 children aged 6 to 7 years who had been born prematurely (mean birth weight 1636 +/- 554 g) but who had required no treatment for pulmonary disease. Results for total lung capacity, FEV1, ratios of functional residual capacity and residual volume to total lung capacity, specific airway conductance, and alveolar plateau slope did not differ in the RDS and control groups. Eight of the 18 children in the RDS group had had radiologic evidence of bronchopulmonary dysplasia at 30 days and oxygen dependence at 30 days, but did not differ from the control group for any of the indices of pulmonary function. However, FEV1 and specific airway conductance were significantly reduced in the premature control group compared with children born at term. Therefore, factors associated with prematurity rather than combined effects of RDS and its treatment determined pulmonary function at age 6 to 9 years.

Diaphragmatic activity is a determinant of postnatal lung growth.

To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity.

The effect of transfusion on lung capacity, diffusing capacity, and arterial oxygen saturation in patients with thalassemia major.

Our previous cross-sectional study of patients with thalassemia major suggested progressive lung changes characterized by low total lung capacity, hypoxemia, and elevated transfer factor for carbon monoxide. We reevaluated nine of the patients for three reasons: to determine the relationship of the previous findings to the immediate effects of blood transfusion; to assess the longitudinal progression of the lung changes; and to evaluate the effect of splenectomy on lung volume changes in these patients, all of whom underwent splenectomy in the interval between the two studies. We found that during the 5- to 6-yr period between studies total lung capacity had decreased significantly (p less than 0.05) from a mean 86% predicted to a mean 79% predicted. However, vital capacity increased significantly (p less than 0.05) from a mean 81% predicted to 88% with no significant change in functional residual capacity. There was no significant immediate effect of transfusion on total lung capacity, vital capacity, or functional residual capacity. However, the diffusion constant for carbon monoxide increased significantly (p less than 0.005) immediately following transfusion and there was a positive correlation between the increase and the amount of blood transfused (r = 0.74, p less than 0.05). Arterial oxygen saturation was below 95% in five of eight patients and increased significantly with transfusion (p less than 0.05). We conclude: 1) thalassemia major and/or its treatment is associated with hypoxemia and a progressive reduction in total lung capacity. 2) Despite the progressive reduction in total lung capacity, splenectomy in patients with thalassemia major increases expiratory reserve volume and thereby increases vital capacity.

Respiratory mechanics in adolescents with idiopathic scoliosis.

Mechanisms causing the reduction in lung capacity commonly found in adolescents with idiopathic scoliosis (IS) have not been understood. In 29 patients with typical thoracic curvatures of mild to moderate degree (less than 60 degrees), total lung capacity (TLC) was a mean 75 +/- 13% (SD) of predicted. The patients could generate only -70 +/- 26 cm H2O (SD) maximal inspiratory airway pressure at function residual capacity, as compared with -102 +/- 28 cm H2O in 21 normal control subjects (p less than 0.001). Studies of lung mechanics in 15 of the patients showed that maximal transpulmonary pressure at TLC was also reduced. Static pressure volume curves were shifted to the right, and both static and dynamic lung compliance were significantly reduced. Although both upstream conductance per TLC and anatomic dead space per TLC were abnormally high, relationships between maximal expiratory flow and static lung recoil were appropriate for age, indicating a normal growth of airway dimensions. From results of the single-breath nitrogen washout procedure, amounts of trapped nitrogen were also normal, indicating that the low lung compliance is not caused by airway closure. After a 5-min period of positive pressure (25 cm H2O) breathing, dynamic compliance increased by a mean of 34% in subjects with low TLC, and by a significantly smaller (p less than 0.05) mean increase of 14% in subjects with normal TLC. The 15 patients were restudied 1 yr after corrective surgery by the Harrington procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term pulmonary effects of total parenteral nutrition in children with cystic fibrosis.

Indices of respiratory muscle strength, pulmonary function, and pulmonary diffusing capacity were measured in 11 malnourished children (age 10 to 17 years) with cystic fibrosis, before and after improvement of nutritional status with supplemental parenteral nutrients for 1 month. During this time, the children received 120% of estimated energy requirements (either 3.75% or 22.5% as lipid) and amino acids 2.5 gm/120 kcal by central venous catheter, plus as much of their usual diet as desired. With nutritional supplementation, body weight, triceps skinfold thickness, and mid-arm muscle circumference increased (mean 15%, 62%, and 95%, respectively). Maximum inspiratory airway pressure also increased (mean 29%; P less than 0.01), suggesting improvement in respiratory muscle strength. However, none of the indices of pulmonary function improved. Pulmonary diffusing capacity did not change during parenteral nutrition regardless of the amount of parenteral energy intake supplied by lipid, but arterial oxygen saturation decreased (mean of 93.5% to 91.5%; P less than 0.005). During the month following parenteral nutrition, weight, skinfold thickness, and mid-arm muscle circumference, but not MIP, decreased and arterial oxygen saturation returned to the initial value (P less than 0.01).

Ventilation distribution and density dependence of expiratory flow in asthmatic children.

Of 114 asthmatic children, 21% had abnormally steep phase III slopes from a modified single-breath oxygen (SBO2) procedure. We hypothesized that the steep slopes reflect inequality of time constants caused by obstruction of peripheral airways and tested this by using a bronchodilator to reduce overall time constants in subgroups of 10 children with steep slopes (SS) and 20 children with normal slopes (NS). Maximum expiratory flow increased by equivalent degrees (0.65-0.70 l/s) in both groups, but slope decreased significantly only in the SS group. Moreover, the single-breath mixing efficiency of inspired oxygen with resident nitrogen was normal in the NS group but significantly low in the SS group. Density dependence of maximum expiratory flow (DD) was abnormally small in the SS group [15 +/- 6% (SD) increase compared with 57 +/- 13% increase in a separate group of normal children] and was independent of the anatomical dead space. In contrast, DD was normal and varied inversely with anatomical dead space (r = 0.62, P less than 0.01) in the NS group. These results indicate that 1) steep SBO2 slopes found in asthmatic children between acute episodes reflect unequal time constants caused by obstruction of peripheral airways and 2) part of the variation in DD among asthmatic children is caused by variation in convective accelerative pressure losses in major airways.