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.

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.

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.

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.

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.

Retinal studies at 446 torr in a hypobaric chamber.

This study was designed to see if retinal haemorrhage occurred after 24 h of decompression to a pressure of 446 torr. Four subjects were studied after 24 h of decompression and had retinal photography and fluorescein angiography performed at rest and following maximum exercise. No haemorrhages or fluorescein leakage was noted, even though the subjects experienced typical symptoms of acute mountain sickness and showed an increase in lung density-consistent with subclinical pulmonary edema. We conclude that 24 h exposure to 446 torr with a period of maximal exercise is an inadequate stress, either in time and/or degree, of hypoxia to produce retinal haemorrhage or leakage, as measured by flourescein.

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.

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.

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.

Maturation of lung function in children with hypopituitarism.

To identify factors that bring about maturation of the respiratory system, we studied pulmonary function in 18 patients 9 to 19 yr of age with severe growth retardation caused by hypopituitarism. In 6 we measured pulmonary pressure-volume (P-V) curves before and after a 4 to 6 yr period of human growth-hormone-induced catch-up growth. Even when size-corrected according to total lung capacity (TLC), all measurements were more appropriate for height than for age. The ratio of functional residual capacity to TLC was low for age (less than 2 SD in 8 of 18 patients), and the ratio of closing capacity to TLC was slightly high for age (108% of predicted, p less than 0.05). The diffusion constant for carbon monoxide and the slope of the nitrogen washout alveolar plateau were both high for age. Lung elastic recoil was low for age; Pst(L) at 60% TLC was less than 2 SD in 3 of the 6 patients studied. During the period of catch-up growth, TLC increased appropriately for height, the slope of the alveolar plateau decreased (1.9 to 1.0% N2 L, p less than 0.01) and Pst(L) at 60% TLC increased (6.3 to 7.9 cm H2O, p less than 0.02). The P-V results indicate that growth of the lungs per se causes the increase in lung elastic recoil previously observed during childhood.

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.

Relationship of lung recoil to lung volume and maximum expiratory flow in normal children.

Thirty-one normal children, aged 6--18 yr, were studied by measurements of static lung volumes, static expiratory pressure-volume (PV) curves, and maximum expiratory flow-volume (MEFV) curves. A theoretical standard volume was used to compare children of differing size and this showed that total lung capacity (TLC) is also a valid standard volume. The shape of the PV curve was found to change so that static elastic recoil at a fixed proportion of TLC was higher in older than in younger children. This was also true of static recoil at functional residual capacity (FRC) and an associated increase in the ratio of FRC to TLC was interpreted as evidence for increase in outward recoil of the chest wall during childhood. Since static recoil at "closing capacity" (CC) remained constant, a decrease in the ratio of CC to TLC was quantitatively explained by the PV shift during childhood. Although maximum expiratory flow at various lung volumes increased in constant proportion to TLC, "upstream conductance" decreased relative to TLC. It was concluded that maturation of the respiratory system is disproportionate in several features during childhood and that these disproportions are likely to be even more prominent during infancy and early childhood.

Changes in distribution of ventilation with lung growth.

We systematically studied the effects of varying preinspiratory lung volumes and expiratory flow rates on the alveolar plateau of the single-breath oxygen test in children and adults. With inhalations of oxygen beginning at functional residual capacity (FRC) compared with residual volume (RV), the slope of phase III increased in 52 of 54 children and 6 of 6 adults (mean increase 29.2%, P less than 0.001) but then decreased at preinspiratory volumes greater than FRC. With maximal expiratory flows, the slopes were smaller than slopes from conventional maneuvers in 14 of 15 children by a mean 24.1%, P less than 0.001. These data suggest that apex-to-base differences in regional lung volume are a major determinant of the slope. Slopes (FRC maneuver) decreased as a function of the height of the children (r = -0.73, P less than 0.001), but differences in nitrogen concentration over the alveolar plateau increased with height (r = 0.70, P less than 0.001). This indicates that the apex-to-base differences in regional lung volume increase with lung size. An estimate of mixing efficiency between resident and inspired gas derived from the alveolar plateau increased with height for both RV (r = 0.40, P less than 0.005) and FRC maneuvers (r = 0.45, p less than 0.005) and was greater for FRC than RV (P less than 0.001). These increases in mixing efficiency are consistent with previously demonstrated decreases in closing volume with growth.

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.

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.

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.

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.

Effects of growth on the diffusion constant for carbon monoxide.

To investigate factors determining the diffusion constant for carbon monoxide (KCO) in normal children, we used the single breath method in 33 healthy children and young adults, 6 to 30 yr of age. In the sitting position, KCO decreased with increasing height (r = -0.59, p less than 0.001), suggesting greater recruitment of pulmonary vascular bed at the apexes in the shorter subjects. Increase in the KCO after taking the supine position was significantly less in the shorter subjects (8% at 120 cm) than in the taller subjects (27% at 170 cm), confirming this mechanism. Ten subjects with pulmonary involvement from cystic fibrosis had normal supine KCO but did not show a normal decrease in the upright position. From an analysis of present and previous data we conclude that (1) decrease in the conventionally measured KCO during childhood reflects a gravity-dependent decrease in recruitment of the pulmonary vascular bed and a decrease in the ratio of alveolar surface area to alveolar volume during growth and (2) diseases associated with hypoxic pulmonary vasoconstriction tend to recruit the pulmonary vascular bed at the apexes, increasing the conventionally measured KCO.