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Background: Spirometry is the gold standard for assessing airway function for clinical studies; however, obtaining high-quality data in young children remains challenging. Since the forced oscillation technique (FOT) requires less subject cooperations, there has been increasing interest in FOT, particularly in young children. We evaluated whether spirometry and FOT in young children provides comparable ability to detect a treatment effect., Methods: We recently reported in a randomized controlled trial that vitamin C compared to placebo treatment of mothers who smoked during pregnancy (MSDP) results in the offspring having significantly higher forced expiratory flows (FEFs) at 5-years of age, as well as significantly less wheeze at 4-6 years of age. In these same offspring, we also measured respiratory impedance using FOT at 8-Hz impedance at 3, 4, and 5 years of age., Results: Although spirometry demonstrated significantly increased FEFs in vitamin C compared to placebo-treatment group at 5 years of age (p < 0.001), we were not able to detect a similar treatment effect using FOT impedance., Conclusions: It may be challenging to obtain technically successful spirometry in preschool children; however, FEFs may provide a better outcome than single-frequency FOT impedance to assess improvements in airway function in these young subjects., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking., Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E., Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age., Measurements and Main Results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume among the three groups. Forced vital capacity was similar among the three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups., Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Antenatal corticosteroids (ACS) administration to pregnant women for threatened preterm labor is standard obstetric care to reduce neonatal respiratory distress syndrome and the associated respiratory morbidity. While ACS stimulates surfactant production in the fetal lung, the effects of ACS upon the subsequent growth and development of the lung are unclear. Follow-up studies outside of the neonatal period have been primarily limited to spirometry, and most subjects evaluated were born prematurely. To our knowledge, no study has assessed both airway and parenchymal function in infants or adults following ACS exposure. We hypothesized that ACS impairs lung growth and performed infant pulmonary function testing, which included spirometry, alveolar volume (V A ) and lung diffusion (D L ). As a pilot study, we limited our assessment to infants whose mothers received ACS for threatened preterm labor, but then proceeded to full term delivery. This approach evaluated a more homogenous population and eliminated the confounding effects of preterm birth. We evaluated 36 full-term infants between 4 to 12 months of age; 17 infants had ACS exposure and 19 infants had no ACS exposure. Infants exposed to ACS had a significantly lower forced vital capacity compared with non-ACS exposed infants (250 vs 313 mL; P = .0075). FEV 0.5 tended to be lower for the ACS exposed group (205 vs 237 mL; P = .075). V A and D L did not differ between the two groups. These findings suggest that ACS may impair subsequent growth of the lung parenchyma., (© 2020 Wiley Periodicals LLC.)

Background: Lung diffusion assessed by the uptake of carbon monoxide (DL CO ) and alveolar volume (V A ) by inert gas dilution are readily assessed in cooperative older subjects; however, obtaining these measurements in infants has been much more difficult. Our laboratory has measured DL CO and V A in sleeping infants using a mass spectrometer, which continuously measures gas concentrations, and demonstrated that infants with bronchopulmonary dysplasia (BPD) have lower DL CO , but no difference in V A compared to full-term controls. The mass spectrometer is expensive and lacks portability; therefore, we evaluated whether measurement of end-expiratory alveolar gas concentrations using a gas chromatograph would provide an alternative approach., Methods: (1) Using our previously digitized data for infants with BPD and full-term controls, DL CO and V A were calculated at end-expiration rather than between 60 and 80% of expired volume, as previously reported. (2) In a new group of infants, DL CO and V A were measured using gas concentrations obtained at end-expiration with a mass spectrometer and a gas chromatograph., Results: (1) Using end-expiratory concentrations, infants with BPD (n = 49) had significantly lower DL CO , but similar V A compared to healthy controls (n = 34) (DL CO : 4.2 vs 4.6 mL/min/mmHg, P = 0.047; V A : 614 vs 608 mL, P = 0.772). (2) Among newly evaluated infants (n = 28), DL CO and V A obtained with a mass spectrometer and a gas chromatograph were highly correlated (R 2  = 0.94 and 0.99, respectively), and were not significantly different for the two analyzers., Conclusion: Measuring DL CO and V A at end-expiration using a gas chromatograph can provide an effective assessment of gas exchange in sleeping infants., (© 2017 Wiley Periodicals, Inc.)

Background: Bronchopulmonary dysplasia (BPD) results from alveolar simplification and abnormal development of alveolar and capillary structure. Survivors of BPD display persistent deficits in airflow and membrane and vascular components of alveolar gas diffusion. Despite being the defining feature of BPD, various neonatal hyperoxia models of BPD have not routinely assessed pulmonary gas diffusion., Methods: To simulate the most commonly-utilized neonatal hyperoxia models, we exposed neonatal mice to room air or ≥90% hyperoxia during key stages of distal lung development: through the first 4 (saccular), 7 (early alveolar), or 14 (bulk alveolar) postnatal days, followed by a period of recovery in room air until 8 weeks of age when alveolar septation is essentially complete. We systematically assessed and correlated the effects of neonatal hyperoxia on the degree of alveolar-capillary structural and functional impairment. We hypothesized that the degree of alveolar-capillary simplification would correlate strongly with worsening diffusion impairment., Results: Neonatal hyperoxia exposure, of any duration, resulted in alveolar simplification and impaired pulmonary gas diffusion. Mean Linear Intercept increased in proportion to the length of hyperoxia exposure while alveolar and total lung volume increased markedly only with prolonged exposure. Surprisingly, despite having a similar effect on alveolar surface area, only prolonged hyperoxia for 14 days resulted in reduced pulmonary microvascular volume. Estimates of alveolar and capillary structure, in general, correlated poorly with assessment of gas diffusion., Conclusion: Our results help define the physiological and structural consequences of commonly-employed neonatal hyperoxia models of BPD and inform their clinical utility. Pediatr Pulmonol. 2017;52:616-624. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Rationale: Asthma is prevalent in children with eosinophilic esophagitis (EoE) estimated at 24-42% in prior studies versus 9% for the general population. However, pulmonary function and airway hyperresponsiveness (AHR) in children with EoE have not been previously defined., Methods: A cross-sectional prospective study was conducted of children ages 7-18 years with EoE and healthy controls. Methacholine bronchial challenge and exhaled nitric oxide were assessed. As measures of atopy and immune activation, peripheral blood was analyzed for total IgE, specific IgE to selected aeroallergens, eosinophil count, and serum cytokines including eotaxin., Results: EoE subjects (n = 33) and healthy controls (n = 37) demonstrated similar, normal baseline spirometry. AHR occurred in 33% of children with EoE and 11% of healthy controls (P = 0.04; 95% confidence intervals [19%, 52%] and [4%, 26%], respectively). The majority of EoE subjects with AHR had no prior diagnosis of asthma. Overall, 69.7% of EoE subjects had either asthma or AHR. For EoE subjects, total serum IgE was the only biomarker associated with a greater risk of AHR (OR = 9.643, 95%CI 1.633, 56.925). EoE subjects with and without asthma were similar to healthy controls in mean levels of serum cytokines (IL-5, IL-9, EGF, FGF-2, eotaxin). In exploratory analyses, the subgroup with EoE and asthma without asthma controller therapy had higher mean FGF-2 than EoE subjects without asthma (110 pg/ml vs. 65 pg/ml, P = 0.0426)., Conclusions: Asthma and AHR may be more prevalent than previous estimates in children with EoE. For subjects with EoE, elevation in serum IgE was associated with a greater risk of AHR., (© 2015 Wiley Periodicals, Inc.)

Previous studies of pulmonary diffusing capacity in healthy children primarily focused upon Caucasian (C) subjects. Since lung volumes in African-Americans (AA) are smaller than lung volumes in C subjects of the same height, diffusing capacity values in AA children might be interpreted as low or abnormal using currently available equations without adjusting for race. Healthy AA (N = 151) and C (N = 301) children between 5 and 18 years of age performed acceptable measurements of single breath pulmonary diffusing capacity for carbon monoxide (DLCO ) and alveolar volume (VA ) according to current ATS/ERS guidelines. The natural log of DLCO and VA were associated with height, gender, age, and race; AA children had lower DLCO and VA compared to C children. Adjustment of DLCO for Hemoglobin (Hgb) resulted in no significant difference in DLCO among these healthy subjects with normal Hgb. In summary, we report prediction equations for DLCO and VA that include adjustment for race (C; AA) demonstrating that AA have lower DLCO and VA compared to C children for the same height, gender, and age., (© 2015 Wiley Periodicals, Inc.)

Rationale: While infants who are born extremely premature and develop bronchopulmonary dysplasia (BPD) have impaired alveolar development and decreased pulmonary diffusion (DLCO), it remains unclear whether infants born less premature and do not develop BPD, healthy premature (HP), have impaired parenchymal development. In addition, there is increasing evidence that pro-angiogenic cells are important for vascular development; however, there is little information on the relationship of pro-angiogenic cells to lung growth and development in infants., Objective: and Methods Determine among healthy premature (HP) and fullterm (FT) infants, whether DLCO and alveolar volume (VA) are related to gestational age at birth (GA), respiratory support during the neonatal period (mechanical ventilation [MV], supplemental oxygen [O2], continuous positive airway pressure [CPAP]), and pro-angiogenic circulating hematopoietic stem/progenitor cells (CHSPCs). We measured DLCO, VA, and CHSPCs in infants between 3-33 months corrected-ages; HP (mean GA = 31.7 wks; N = 48,) and FT (mean GA = 39.3 wks; N =88)., Result: DLCO was significantly higher in HP than FT subjects, while there was no difference in VA , after adjusting for body length, gender, and race. DLCO and VA were not associated with GA, MV and O2; however, higher values were associated with higher CHSPCs, as well as treatment with CPAP., Conclusion: Our findings suggest that in the absence of extreme premature birth, as well as BPD, prematurity per se, does not impair lung parenchymal development., (© 2014 Wiley Periodicals, Inc.)

Pulmonary interstitial glycogenosis (PIG) is an idiopathic interstitial lung disease of infants. The underlying pulmonary pathophysiology of PIG has not been well characterized. Herein we report a term-gestation infant who presented with persistent tachypnea and hypoxia. A chest CT scan demonstrated a diffuse ground glass appearance and lung biopsy demonstrated increased alveolar septae cellularity with glycogen-containing cells, consistent with a diagnosis of PIG. At 3 months of age, pulmonary function testing included: pre- and post-bronchodilator forced expiratory flows using the raised-volume technique and the ratio of pulmonary diffusing capacity for carbon monoxide to alveolar volume (DLCO /VA ). He was prescribed 5 days of oral prednisolone (2mg/kg/day) and pulmonary function testing (PFT) was repeated at 5, 13, and 20 months of age. Initial PFTs demonstrated reduced forced vital capacity (FVC: Z-score = -2.36) and an increased ratio of forced expiratory volume in 0.5 sec to FVC (FEV0.5/FVC: Z-score = 1.15) with no significant change following an inhaled bronchodilator. There was also a marked reduction in DLCO /VA (Z-score = -4.74) compared to age-matched controls. Follow-up demonstrated progressive clinical improvement as well as an increase in Z-FVC and normalization of DLCO /VA . Our in vivo physiological findings are consistent with previous reports that symptom resolution correlated with histological thinning of the alveolar septae upon repeat lung biopsy. The restrictive lung disease we observed is consistent with expected reduced compliance of an alveolar interstitial lung process like PIG, whereas the absence of a reduction in FEV0.5/FVC confirms the absence of obstructive airway disease., (© 2013 Wiley Periodicals, Inc.)

Background: Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age., Methods: Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age., Results: We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age., Conclusions: While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness., (© 2013 Wiley Periodicals, Inc.)

Children and adults residing at high altitude (HA) compared to low altitude (LA) have larger lung volumes; however, it is unknown whether this response to chronic hypoxia begins early in life. Our objective was to determine whether infants and toddlers at HA have larger lung volumes compared to infants and toddlers at LA. Oxygen saturation (SaO2 ), functional residual capacity (FRC), as well as serum levels of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) were measured in infants and toddlers from HA (N = 50; 3,440 m) and LA (N = 35; 440 m). There were no significant differences in somatic size for HA and LA subjects; however, HA subjects had significantly lower SaO2 (88.5% vs. 96.7%; P < 0.0001). Subjects at HA had significantly greater FRC compared to subjects at LA (group mean: 209 and 157 ml; P < 0.0001), adjusting for body length. Male infants at HA had a significantly greater FRC compared to males at LA (57 ml; P-value < 0.001); however, the increase in FRC for females at HA compared to LA was not significant (20 ml; P-value = 0.101). VEGF and EPO were significantly higher for subjects at HA compared to LA with no gender differences. In summary, infants and toddlers at HA have lower oxygen saturations, higher serum levels of VEGF and EPO, and higher FRC compared to subjects at LA; however, chronic hypoxia appears to generate a more robust response in lung growth in male compared to female infants early in life., (© 2013 Wiley Periodicals, Inc.)

Previous studies of pulmonary diffusing capacity in children differed greatly in methodologies; numbers of subjects evaluated, and were performed prior to the latest ATS/ERS guidelines. The purpose of our study was to establish reference ranges for the diffusing capacity to carbon monoxide (DL(CO) ) and alveolar volume (V(A) ) in healthy Caucasian children using current international guidelines and contemporary equipment. Healthy children from the United States (N = 303) and from Australia (N = 176) performed acceptable measurements of single breath pulmonary diffusing capacity and alveolar volume according to current ATS/ERS guidelines. The natural log of DL(CO) and V(A) were associated with height, age and an age-sex interaction term, while DL(CO) /V(A) was related to height and the age-sex interaction term only. Adjustment of DL(CO) for hemoglobin (n = 303; USA data only) resulted is a small but significant decrease in DL(CO) of ∼1% but did not significantly alter the regression equations. In this dataset there was no influence of center for DL(CO) or DL(CO) /V(A) , while Australian children had a statistically smaller V(A) (mean difference 0.14 L after accounting for height, age and age-sex; P = 0.012). We report that diffusing capacity outcomes can be collated from multiple centers using similar equipment and collection protocols. Using collated data we have derived regression equations for pulmonary diffusing capacity outcomes in healthy Caucasian children aged 5-19 years., (Copyright © 2011 Wiley Periodicals, Inc.)

Some studies have suggested that lung clearance index (LCI) is age-independent among healthy subjects early in life, which implies that ventilation distribution does not vary with growth. However, other studies of older children and adolescents suggest that ventilation becomes more homogenous with somatic growth. We describe a new technique to obtain multiple breath washout (MBWO) in sedated infants and toddlers using slow augmented inflation breaths that yields an assessment of LCI and the slope of phase III, which is another index of ventilation inhomogeneity. We evaluated whether ventilation becomes more homogenous with increasing age early in life, and whether infants with chronic lung disease of infancy (CLDI) have increased ventilation inhomogeneity relative to full-term controls (FT). FT (N = 28) and CLDI (N = 22) subjects between 3 and 28 months corrected-age were evaluated. LCI decreased with increasing age; however, there was no significant difference between the two groups (9.3 vs. 9.5; P = 0.56). Phase III slopes adjusted for expired volume (S(ND)) increased with increasing breath number during the washout and decreased with increasing age. There was no significant difference in S(ND) between full-term and CLDI subjects (211 vs. 218; P = 0.77). Our findings indicate that ventilation becomes more homogenous with lung growth and maturation early in life; however, there is no evidence that ventilation inhomogeneity is a significant component of the pulmonary pathophysiology of CLDI., (Copyright © 2011 Wiley Periodicals, Inc.)

We describe a method for measuring carbon monoxide diffusing capacity (DL(CO)) and alveolar volume (V(A)) in sleeping infants, using a single 4-sec breath-hold technique. The breath-hold maneuver is obtained by inducing a respiratory pause of the respiratory system. Several inflations of the respiratory system with room air to a lung volume with an airway pressure of 30 cmH2O (V30) inhibit inspiratory effort. The respiratory system is then inflated with a test gas containing helium and a stable isotope of carbon monoxide (C18O), and a respiratory pause is maintained for 4 sec and followed by passive expiration to functional residual capacity. Concentrations of helium and C18O are continuously measured with a mass spectrometer. Twelve healthy infants between 6-22 months of age were evaluated. For 9 of 12 subjects, duplicate measurements of alveolar volume at 30 cmH2O (V(A30)) and DL(CO) were within 10%, which are the recommendations for older children and adults. Among these 9 subjects, values of V(A30) and DL(CO) increased with increasing body length (r2 = 0.82 and 0.79, respectively). The remaining 3 subjects had two values within 10-15%. Measurement of V(A) and DL(CO) with the single breath-hold technique at an elevated lung volume offers the potential to assess growth and development of the lung parenchyma early in life., (Copyright 2006 Wiley-Liss, Inc.)

The purpose of this study was to examine lung function and bronchodilator responsiveness in infants with a history of prematurity and bronchopulmonary dysplasia (BPD), using the raised volume rapid thoracoabdominal compression technique as well as with whole-body plethysmography. Spirometric measurements were obtained in 28 infants with a history of BPD, defined as preterm birth with O2 requirement at 36 weeks postmenstrual age (gestational age at birth, 26.4 +/- 2.1 weeks, mean +/- SD; birthweight, 898 +/- 353 g; age at study, 68.0 +/- 35.6 weeks). Fractional lung volumes were measured in 27 subjects. Values were expressed as percentage of predicted normal values. Compared to normal infants, those with a history of BPD exhibited decreases in forced expiratory flows including forced expiratory volume in 0.5 sec (76.3 +/- 19.6%), forced expiratory flow at 75% of expired forced vital capacity (FEF75; 59.5 +/- 30.7%), and FEF(25-75) (74.0 +/- 26.8%; P<0.01 for all). Functional residual capacity (107.9 +/- 25.3%), residual volume (RV, 124.5 +/- 42.7%), and RV/total lung capacity (RV/TLC, 128.2 +/- 35.3%) were increased in infants with a history of BPD (P<0.05 for each). There was no difference in TLC between groups. Seventeen infants were studied both pre- and postalbuterol, and 6 (35%) demonstrated significant bronchodilator responsiveness. Infants with recurrent wheezing showed greater expiratory flow limitation, hyperinflation, and airways responsiveness, whereas those without wheezing showed only modest airway dysfunction. We conclude that infants with a history of BPD have pulmonary function abnormalities characterized by mild to moderate airflow obstruction and air trapping., (Copyright 2004 Wiley-Liss, Inc.)

SUMMARY. The detection of early airway disease in infants with cystic fibrosis (CF) may lead to earlier intervention and an improved prognosis. We hypothesized that the ratio of maximal expiratory flows while breathing a mixture of helium and oxygen (heliox) and air, referred to as density dependence (DD), would identify early airway disease in infants with CF who have normal lung function. We also hypothesized that these infants with CF might be better differentiated from normal infants when the flows breathing heliox are compared instead of room air flows. We evaluated 10 infants with CF and 21 infants without CF and with normal lung function, defined as a forced vital capacity (FVC) and forced expiratory flows between 25-75% of expired volume (FEF(25-75)) of greater than 70% predicted (z-score > -2.0). Full forced expiratory maneuvers by the rapid thoracic compression technique were obtained while breathing room air and then heliox. Flow at 50% and 75% of expired volume (FEF(50), FEF(75)), FEF(25-75), and FVC were calculated from the flow volume curve with patients and control subjects breathing each gas mixture. The ratio of heliox to air flow at FEF(50) and FEF(75) was calculated (DD(50), DD(75)), and the point where the two flow-volume curves crossed (V(iso) V') was also measured. DD parameters did not distinguish the infants with CF from the infants without CF; length-adjusted FEF(50) breathing air was significantly lower in the infants with CF compared to the infants without CF (P < 0.05). Length-adjusted flows breathing heliox did not distinguish the two groups. We conclude that the lower FEF(50) value may reflect early airway obstruction in healthy infants with CF, and that measurements obtained with the less dense gas mixture did not improve detection of airway disease in this age group., (Copyright 2001 Wiley-Liss, Inc.)

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized beta-agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V'mak,FRC) were measured on admission, on Day 10 of hospitalization, and as outpatients 1-2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z-scores. Upon admission flows were decreased, and FRC was increased in both groups; there were no differences between the groups. The change in pulmonary function from admission to Day 10 of hospitalization was not different for the two groups. From admission to outpatient follow-up after hospitalization, there was a significant increase in flows for the steroid group, but not for the placebo group. In addition, the direction of change in FRC was significantly different for the two groups; the steroid group had a small decrease in FRC, while the placebo group had a small increase in FRC. These findings suggest that the addition of intravenous hydrocortisone to the standard treatment of CF infants hospitalized for a LRI may produce a greater or a more sustained improvement in lung function following hospitalization.

We evaluated 34 infants with bronchiolitis, (17 of both genders; mean age, 4.6 mos; ranges, 0.7-14.5 mos). The 20 inpatients were significantly younger than the 14 outpatients (2.6 vs. 8.2 months, P < 0.05), and more females were inpatients. Forced expiratory flows at functional residual capacity (VmaxFRC) were obtained at baseline, after aerosolized normal saline (NS), and metaproterenol (0.025 mL/kg in 2 mL NS). Flows were expressed as Z-scores, the difference between the measured and predicted flows, divided by the standard deviation for the predicted value. At baseline, outpatients were more obstructed than inpatients (-1.64 vs. -0.95, P < 0.05), infants > 2 months old were more obstructed than infants < or = 2 months old (-1.54 vs. -0.80, P < 0.05), and males more than females (-1.45 vs. -1.02, P < 0.05). Following NS the whole group had a small but significant decrease in Z-scores (-1.23 to -1.31, P < 0.05). Following metaproterenol, the younger infants had significantly (P < 0.05) higher Z-scores compared to baseline and NS (-0.80 vs. -0.86 vs. -0.59). However, no significant changes occurred in older infants. Females also had an increased flow after metaproterenol and were less obstructed than after NS (-1.11 vs. -0.86, P < 0.015). In males no increased flows occurred after metaproterenol (-1.45 vs. -1.48). Bronchodilator responsiveness did not relate to severity of airway obstruction, history of family asthma, allergy, or passive smoke exposure. We conclude that inhaled metaproterenol improves airway function in a subgroup of infants with bronchiolitis, but the subgroup could not clearly be identified because age and gender were confounding factors.

Thirty-two infants with cystic fibrosis (CF) had pulmonary function testing and chest radiographs at the time of diagnosis and on average 1 year later, when they had no acute respiratory symptoms. At diagnosis, 14 of 32 infants had respiratory symptoms (RESP) and 18 did not have respiratory symptoms (NRESP). There were no significant differences in age, weight, or length between the RESP and NRESP groups. At diagnosis, the RESP group had significantly lower forced expiratory flows compared to the NRESP group (41 +/- 32% vs. 98 +/- 48% predicted); however, there were no significant differences in functional residual capacity or chest radiographic scores. Between diagnosis and follow-up, the NRESP group had no significant change in pulmonary function but a decline in chest roentgenographic (CXR) scores (22 +/- 2 to 21 +/- 2). For infants in the RESP group, there were no significant changes in FRC or CXR score. Maximal expiratory flow at functional residual capacity (Vmax FRC) rose from diagnosis to 1 year follow-up (41 +/- 32% to 74 +/- 27% predicted; P < 0.002); however, at follow-up flows for the RESP group remained significantly lower than flows for the NRESP group (74% vs. 113% predicted; P < 0.0005). For the 32 infants with CF, there was significant correlation between percent predicted Vmax FRC at follow-up and at diagnosis (r = 0.47; P < 0.02). Those infants with lower percent predicted flows at diagnosis were more likely to have lower percent predicted flows 1 year later.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway responsiveness of infants is evaluated during sleep and the infants inhale the bronchial challenge agent via the nasal airway. Since stimulation of the nasal airway may produce bronchoconstriction, it is unclear whether the observed response in the infants results from deposition of the aerosol in the lower airways or from stimulation of nasal receptors. Therefore, in 6 healthy infants we compared the changes in partial expiratory flow-volume (PEFV) curves produced by aerosol inhalation of methacholine and the changes produced by instillation of equivalent doses of methacholine liquid into the nares. Following aerosol, the peak expiratory flow and the flow at functional residual capacity decreased, PEFV curves became concave in shape, and the oxygen saturation (SaO2) decreased. The highest methacholine concentration inhaled by any infant was 1.25 mg/mL. In contrast to aerosol delivery, a maximal methacholine concentration of 10.0 mg/mL was instilled into the nares of all 6 infants without any change in maximal flow at functional respiratory capacity (VmaxFRC) or SaO2. There was a significant decrease in peak flow and flattening of the PEFV curves at higher lung volumes; however, the PEFV curve remained convex in shape at the lower lung volumes. The changes in the PEFV curve following nasal instillation of methacholine are consistent with an increase in nasal resistance and no change in the lower airways. We conclude that the bronchoconstriction observed following inhaled methacholine does not result from stimulation of nasal receptors.

Maximal bronchoconstriction in normal adults produces only small reductions in pulmonary function; however, in normal infants severe airway obstruction limits testing to low agonist concentrations. In this study, maximal pulmonary response to methacholine was evaluated in 5 immature (1 month old) and 5 mature (6 months old) rabbits. Animals were anesthetized, paralyzed, and mechanically ventilated via a tracheostomy tube. Changes in pulmonary function were assessed from maximal deflation flow volume curves following inhalation of doubling concentrations of methacholine between 0.6 and 320 mg/mL. Following 320 mg/mL methacholine, the immature rabbits had a greater percent decline in forced vital capacity (FVC) than the mature animals (55 +/- 15% vs. 36 +/- 10%; P < 0.05). At 50% FVC, isovolume flows were measurable in the 5 mature rabbits, and 4 of 5 had plateaus in their dose-response curves. At the higher methacholine doses, only 1 of 5 immature animals had measurable isovolume flows because of the decrease in FVC. There was no significant difference between immature and mature animals in the methacholine dose required to decrease baseline flows by 50%. We conclude that in rabbits maturation affects maximal pulmonary response but not the sensitivity to methacholine.

Forced expiratory flows at functional residual capacity (VmaxFRC) by the rapid compression technique and functional residual capacity (FRC) by the helium dilution technique were assessed in 112 normal infants with a mean age of 10.7 months (range, 1.0-31.0). In predicting FRC, log transformation was appropriate and body length was the best predicator. For VmaxFRC, age was a better predictor than length, and logarithmic transformation was not required. In(FRC) = -5.465 + 2.49 x In(length) SD = 0.178; r2 = 0.83 VmaxFRC = -397 + 9.36 x (age) SD = 88; r2 = 0.52 There were no gender differences for FRC or VmaxFRC; however, male infants exposed to passive cigarette smoke tended to have lower flows than male infants not exposed (P < 0.07). This study establishes normative values for VmaxFRC and FRC in infants between 1 and 31 months of age, and suggests that passive cigarette smoke exposure has an adverse effect upon forced expiratory flows in male infants.

In infants and very young children, functional residual capacity (FRC) is the lung volume most frequently measured and gas dilution techniques are most frequently used to measure FRC. We compared measurements of FRC by helium dilution (FRCHe) and nitrogen washout (FRCN2) in a lung model of known volumes (20, 40, 60, 80 mL) in 8 normal infants (NL), 8 infants with acute respiratory illness (ARI), and 7 infants with chronic lung disease (CLD). In the model lung, measurements of FRCHe had a significantly greater coefficient of variation compared to FRCN2 (6.5 vs 1.5%, P less than 0.02), but there was no such difference in the results from all infants combined (6.5 vs 6.2%). In the model lung, the difference between known volumes and the measured values was significantly different from zero only for FRCHe at 20 mL (-4.4 mL, P less than 0.02). For both FRCHe and FRCN2, the slopes of the regression equations were 0.99 and the intercepts not significantly different from zero. We conclude that techniques for measuring FRCHe and FRCN2 yield accurate, reproducible, and comparable results in normal, healthy infants and very young children, and in those with respiratory disease.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.

Partial expiratory flow-volume (PEFV) curves obtained by the rapid compression technique were employed to assess airway function in three infants with three different lesions of the central airways (vascular ring, congenital tracheal stenosis, subglottic polyp). Preoperatively, all three demonstrated severe flow limitation with a relatively constant forced expiratory flow over the tidal volume range. Postoperatively the PEFV curves changed to a normal convex shape, and the maximal expiratory flows at functional residual capacity (VmaxFRC) returned to normal. The PEFV curve adds to our physiologic assessment of the severity of the central airway obstruction in infants and to the efficacy of our therapeutic intervention.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.