Chronic aspiration without gastroesophageal reflux as a cause of chronic respiratory symptoms in neurologically normal infants.

OBJECTIVE: To describe 13 neurologically normal infants with chronic respiratory symptoms who had swallowing dysfunction with silent chronic aspiration without gastroesophageal reflux (GER) as the cause of their respiratory symptoms. BACKGROUND: Infants with neurologic disorders and infants with GER are known to have chronic respiratory symptoms. Isolated swallowing dysfunction and aspiration without GER in neurologically normal infants have not been widely reported. DESIGN: Retrospective chart review. SETTING: A tertiary pulmonary-care center at a children's hospital. PATIENTS: One hundred twelve otherwise healthy infants referred for respiratory symptoms who underwent esophageal pH studies and videofluoroscopic swallow studies (VSSs). METHODS: The records of infants referred between January 1997 and December 1999 to the Department of Pediatric Pulmonology who underwent 24-h esophageal pH monitoring and VSS as part of an evaluation for recurrent stridor and/or wheezing were reviewed. Significant GER was diagnosed if the percentage of time with esophageal pH < 4 was > 6%. Infants included in the study presented with recurrent respiratory symptoms, were born at term, were neurologically normal, had normal results of esophageal pH studies, but had abnormal results of VSSs (n = 13). RESULTS: All 13 infants presented with a variety of recurrent respiratory symptoms including wheezing and intermittent stridor. Ten of 13 infants had spitting and/or choking episodes with feeding. The mean (+/- SD) age at the onset of symptoms was 2.0 +/- 1.6 months, and the mean age at VSS was 5.9 +/- 3.4 months. All 13 infants had normal results of 24-h esophageal pH studies but had abnormal results for VSSs. All infants had evidence of swallowing dysfunction and direct silent aspiration of liquids with thin consistency. Six infants also were aspirating liquids with thick and/or semi-thick consistencies. None of the infants had evidence of structural anomalies on esophagograms. Nine infants were treated with thickened food, and in four infants oral feedings were stopped. Three of these infants required nasojejunal feeding, and one infant required gastrostomy tube feeding. VSSs were repeated every 3 months. In all infants, swallowing dysfunction resolved within 3 to 9 months. All infants tolerated the resumption of oral feeding. Videofluoroscopic documentation of the resolution of aspiration was followed by the resolution of respiratory symptoms in all infants. CONCLUSION: There is a subgroup of otherwise healthy infants, presenting with wheeze and/or stridor, who have isolated swallowing dysfunction and silent aspiration as the cause of their respiratory symptoms.

Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis.

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.

Comparison of high-frequency chest wall oscillation and oscillating positive expiratory pressure in the home management of cystic fibrosis: a pilot study.

Enhanced airway clearance is thought to result in better-maintained pulmonary function in cystic fibrosis (CF). Postural drainage, percussion, and vibration (PDPV) have been the primary airway clearance technique (ACT) employed in CF for over 40 years. Two new airway clearance modalities are high-frequency chest wall oscillation (HFCWO) and oscillating positive expiratory pressure (OPEP). This pilot study was undertaken to evaluate the efficacy of these techniques during home use, assess patient satisfaction with them as compared to PDPV, and assess the feasibility of performing a definitive comparative trial. The prospective, randomized, multicenter crossover trial was conducted at three urban academic CF Care Centers. Twenty-nine CF patients, 9-39 years of age, participated. Subjects performed 4 weeks each of HFCWO and OPEP following 2-week lead-in/washout periods. Spirometry, lung volumes, National Institutes of Health and Petty Scores, and a satisfaction survey were performed at baseline and after each treatment period. An ACT preference survey was completed at the conclusion of the study. Twenty-four subjects completed both therapies. There were no statistically significant differences between therapies for spirometry, lung volumes, or clinical scores. No significant safety issues arose during the study period. Compliance between therapies was similar. Significant differences among therapies existed in patient satisfaction. Given a choice of therapy, 50% of subjects chose HFCWO, 37% OPEP, and 13% PDPV. This study suggests that HFCWO and OPEP are safe and as effective as patients' routine therapies when used for airway clearance in a home setting. Patient satisfaction and preference differ among ACTs and should be considered when prescribing home therapy. A definitive, multi-center, comparative study evaluating long-term efficacy of these techniques is feasible.

Lateral thoracic expansion for Jeune's syndrome: midterm results.

BACKGROUND: In 1995, we reported the use of lateral thoracic expansion in a patient with symptomatic Jeune's asphyxiating thoracic dystrophy. We have subsequently used lateral thoracic expansion 16 times on 10 patients during 7 years. This article reports our outcomes and provides surgical details. METHODS: Charts of all patients undergoing lateral thoracic expansion were reviewed. Eight of the 10 patients had symptomatic Jeune's syndrome. The other 2 had similar thoracic deformities limiting thoracic capacity. In half of the patients the procedures were performed bilaterally. RESULTS: All patients older than 1 year of age were symptomatically benefited by lateral thoracic expansion. Functional and anatomic measurements documented thoracic enlargement in several patients who had comparable preoperative and postoperative studies. However, 2 infants with significant underlying airway disease did not improve and went on to succumb to that aspect of their disease despite enlargement of the thorax. Fracture of the titanium ministruts has been a recurrent problem, and we now use larger struts. CONCLUSIONS: Lateral thoracic expansion is a safe and effective procedure in selected patients with Jeune's syndrome older than 1 year of age as judged by short-term and midterm follow-up. More experience and longer follow-up are required to discern the place of the lateral thoracic expansion in the overall management of these patients.

Bronchodilator responsiveness in normal infants and young children.

UNLABELLED: Several studies have demonstrated that normal infants exhibit bronchoconstriction after inhalation of nonspecific agonists and that the induced airway narrowing can be reversed by the inhalation of a beta-agonist. However, there are very limited data on baseline airway tone and the airway response to a beta-agonist in this subject population. The purpose of our study was to evaluate in normal infants baseline airway responsiveness to the inhaled beta-agonist, albuterol, using changes in maximal expiratory flows. Forty-one healthy infant volunteers with no history of respiratory disease or recurrent wheezing (ages 5.4 to 141.4 wk) were studied. Maximal expiratory flow- volume curves were obtained at baseline and 10 min after inhalation of albuterol (n = 28) or placebo (n = 13) using a metered-dose inhaler with a spacer. The mean percent change was significantly greater (p < 0.05) in the albuterol versus placebo group for FEV(0.5) (2.2% versus -1.5%), FEF(75%) (10.6% versus -3.1%), and FEF(85%) (12.9% versus 0.5%). Six of 28 albuterol-treated infants demonstrated increases in FEF(75%) greater than two standard deviations from the mean change in FEF(75%) seen in the placebo group. These infants were younger and more frequently exposed to maternal smoking during pregnancy. We conclude that normal healthy infants have overall levels of baseline airway tone that are similar to that reported in adults and older children; however, among the infants we evaluated the response to an inhaled bronchodilator was greatest in the youngest infants and in those exposed to tobacco smoking. KEYWORDS: airway responsiveness; asthma; tobacco smoke; infant pulmonary function; bronchodilator

Technique and clinical applications of full-inflation and end-exhalation controlled-ventilation chest CT in infants and young children.

BACKGROUND: The inability of young children to cooperate with breath holding limits the usefulness of chest CT. OBJECTIVE: To describe the technique and utility of a non-invasive method called controlled-ventilation CT (CVCT) for obtaining motion-free full-inflation and end-exhalation images of the lung in infants and young children. MATERIALS AND METHODS: Eighty-seven children (ages 1 week to 5 years, mean 2 years) underwent CVCT of the chest during suspended respiration at full-lung inflation and end-exhalation for a variety of clinical indications. Respiratory pauses were produced using conscious sedation and positive-pressure face-mask ventilation. Forty-one of 87 children had recordings of respiratory motion during CVCT. RESULTS: Respiratory pause lengths increased with age (P < 0.003), were highly reproducible (r = 0.85), and lasted sufficiently long to be practical for full-inflation (24 +/- 9 s) and end-exhalation (12 +/- 5 s) CT scanning. Full-inflation CVCT was useful in evaluating tracheal and bronchial stenosis, bronchial wall thickening, early bronchiectasis, bronchial fistula, extent of interstitial fibrosis, and lung nodules. End-exhalation CVCT was useful in evaluating tracheomalacia and air trapping. CONCLUSION: Controlled-ventilation chest CT is a practical and reliable technique that promises to be clinically useful for a number of clinical indications in infants and young children.

Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.

Compression of the trachea by the innominate artery in a 2-month-old child.

SUMMARY. We utilized improved methods for assessing airway structure and function to define the clinical significance of the innominate artery syndrome. Both infant pulmonary function tests (IPFT) and noninvasive controlled ventilation computed tomography (CVCT) were used, along with traditional diagnostic techniques in a 2-month-old child with compression of the trachea by the innominate artery. These tests provided objective documentation of functional impairment before surgery and improvement postoperatively. These tests should aid in the understanding of this controversial syndrome and help to further define treatment options.

Static compliance of the respiratory system in healthy infants.

We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.

Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis.

Pseudomonas aeruginosa lung infection is an important cause of morbidity and mortality in cystic fibrosis (CF). Longitudinal assessment of the phenotypic changes in P. aeruginosa isolated from young children with CF is lacking. This study investigated genotypic and phenotypic changes in P. aeruginosa from oropharynx (OP) and bronchoalveolar lavage fluid (BALF) in a cohort of 40 CF patients during the first 3 years of life; antibody response was also examined. A high degree of genotypic variability was identified, and each patient had unique genotypes. Early isolates had a phenotype distinct from those of usual CF isolates: generally nonmucoid and antibiotic susceptible. Genotype and phenotype correlated between OP and BALF isolates. As determined by culture, 72.5% of patients demonstrated P. aeruginosa during their first 3 years. On the basis of combined culture and serologic results, 97.5% of patients had evidence of infection by age 3 years, which suggests that P. aeruginosa infection occurs early in CF and may be intermittent or undetectable by culture.

Adult-type pulmonary function tests in infants without respiratory disease.

A new method that permits the measurement of adult-type maximal expiratory flow-volume curves and fractional lung volumes in sedated infants was recently described. The purpose of this study was to define the normal range for these new measures of pulmonary function in infants and young children. Measurements of forced expiratory flows and fractional lung volume were made on 35 occasions in 22 children (ages 3-120 weeks) without respiratory disease. Maximal expiratory flow-volume curves were measured by the raised lung volume, thoracoabdominal compression technique. Functional residual capacity (FRC) was measured plethysmographically. Measurements of total lung capacity (TLC), residual volume (RV), FRC, forced vital capacity (FVC), and forced expiratory flows at 25, 50, 75, 85, and between 25% and 75% of expired FVC (FEF(25), FEF(50), FEF(75), FEF(85), and FEF(25-75), respectively) all increased in relation to infant length (P<0.001). RV/TLC, FRC/TLC, and FEF(25-75)/FVC declined in relation to increasing length (P<0.001). The forced expiratory flow and fractional lung volume measurements using this method were similar to previously reported estimates using other methods. These estimates represent a reasonable reference standard for infants and young children with respiratory problems.

Flow limitation in infants assessed by negative expiratory pressure.

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H(2)O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique.

Forced expiratory flows and volumes in infants. Normative data and lung growth.

Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Induction of interleukin-8 release by lung epithelium with cystic fibrosis epithelial lining fluid is marginally affected by inhibitors of interleukin-1beta.

Interleukin-1beta (IL-1beta) and neutrophil elastase (NE) are present in the epithelial lining fluid (ELF) of patients with cystic fibrosis (CF). Both factors activate surrounding cells including lung epithelial cells, causing release of IL-8, a potent chemoattractant for neutrophils. Previous studies showed up-regulation of IL-8 release by lung epithelial cells as a function of NE in CF; however, few studies addressed the relationship between IL-1beta and activation of lung epithelial cells in CF lungs. Confluent layers of A549 cells, a type II-like human lung epithelial cell line, were incubated overnight with IL-1beta (0-5 ng/ml) or NE (100 nM), and supernatants were analyzed for IL-8 by enzyme-linked immunosorbent assay (ELISA). Both IL-1beta and NE led to a significant increase in IL-8: 12.8 +/- 2.8 ng/ml and 0.8 +/- 0.3 ng/ml, respectively. Next, bronchoalveolar lavage (BAL) samples were obtained from one healthy adult volunteer and six patients with CF and measured for IL-8 and IL-1beta concentrations by ELISA. Both IL-8 (range 169.00 +/- 56.57 to 1742.04 +/- 338.98 pg/ml) and IL-1beta (range 0-24.26 +/- 0.52 pg/ml) were detected in CF specimens, whereas neither was detected in the volunteer's specimen. Normal and CF BALs then were incubated overnight at a 1:10 dilution with confluent A549 cells. Analysis by ELISA of cell-free supernatants revealed increased IL-8 production from cells stimulated with CF BALs only. Similar experiments were performed with BAL supernatants that had been incubated with soluble IL-1 type II receptor, soluble IL-1 receptor antagonist, or a peptide inhibitor of NE. Addition of IL-1 inhibitors had a marginal effect on the amount of IL-8 release after incubation with CF BAL samples, whereas inhibition of NE had no effect. Our results indicate that other factors present in ELF in CF account for IL-8 release from lung epithelial cells.

Density dependence of forced expiratory flows in healthy infants and toddlers.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22-1.54) and 1.23 (1.02-1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.

Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis.

The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age. For predicting any growth of Pseudomonas aeruginosa (Pa) from the lower airway in subjects /=10(3) or >/=10(5) cfu/mL. Specificity for Pa declined significantly with increasing age. In children with CF <5 years of age, the specificity and negative predictive value of OP cultures for Pa are high, while the sensitivity and positive predictive value are poor. Thus, in this age range, a negative throat culture is helpful in "ruling out" lower airway infection with Pa. However, a positive culture does not reliably "rule in" the presence of Pa in the lower respiratory tract. These findings may have implications for study design and interpretation as well as clinical management of young children with CF.

Rate constant for forced expiration decreases with lung growth during infancy.

Airway caliber and lung volume (VL) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow-volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV(0.5)/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their VL and that VL increases more rapidly than airway caliber early in life.

Lungs in infants and young children: improved thin-section CT with a noninvasive controlled-ventilation technique--initial experience.

Three sedated young children underwent thin-section computed tomography (CT) of the chest while breathing and during controlled respiratory pauses induced by means of a step increase in positive-pressure ventilation applied via a face mask. Motion-free inspiratory and expiratory thin-section CT images were successfully acquired during 8-12-second respiratory pauses. This simple, reproducible technique produced thin-section CT images that were clearer and more clinically useful than those obtained during quiet tidal breathing.

Passive respiratory mechanics in healthy infants. Effects of growth, gender, and smoking.

This investigation characterizes the normal growth, variability, and effects of gender and smoking on passive respiratory mechanics in healthy infants. Passive respiratory mechanics were assessed at 193 test sessions on 127 infants (55 boys, 72 girls) between 2 wk and 18 mo of age using the single-occlusion passive flow-volume technique. Respiratory compliance (Crs) increased significantly with increasing infant length, whereas respiratory resistance (Rrs) declined. No significant gender differences were apparent for Crs, although there was a tendency for this measure to be both lower at birth and increase at a slower rate in girls than in boys. Rrs was significantly higher at birth in infant boys than in infant girls, but the rate of the normal decline in Rrs during the first 18 mo also occurred at a significantly greater rate in boys. The passive respiratory time constant (Trs) overall showed little change over this age range, but it was both lower near birth and increased at a significantly greater rate versus infant length in girls than in boys. Maternal smoking during pregnancy was associated with lower levels of Rrs at birth, as well as with significantly slower growth of Crs and natural decline of Rrs in the first 18 mo of life. These data suggest that infant girls may have more mature respiratory mechanics at birth, but that postnatal growth/maturation may be faster in boys.

Flow limitation in normal infants: a new method for forced expiratory maneuvers from raised lung volumes.

Forced expiratory maneuvers generated by rapid thoracic compression have been used to assess airway function in infants. It remains unclear whether flow limitation can be achieved in healthy infants because low pressure transmission across the chest wall and inspiratory effort may limit the maximum transpulmonary pressure developed during the maneuver. We have found that several rapid inflations to a lung volume set at an airway pressure of 30 cmH2O (V80) briefly inhibit respiratory effort and allow forced expiration to proceed from V80 to residual volume. We used a water-filled esophageal catheter to measure isovolume pressure-flow curves in seven healthy infants (3-88 mo). Forced vital capacity (FVC) was defined as the volume between V80 and residual volume. Pressure transmission between the compression jacket and the esophagus decreased with decreasing lung volume and averaged 60 and 37% at 50 and 75% of expired FVC, respectively. Subjects demonstrated plateaus in their isovolume pressure-flow curves at 50% of expired FVC and lower lung volumes. We conclude that this new methodology enables forced expiratory maneuvers to achieve flow limitation in healthy infants over at least the lower portion of their lung volume.