Howard B. Panitch

Bronchiolitis in infants.

Bronchiolitis is a common cause of wheezing among infants. Respiratory syncytial virus (RSV) is the most common infectious agent to cause bronchiolitis, and RSV infection accounts for more than 125,000 hospitalizations per year in the United States. Beyond supportive measures, the care of infants with bronchiolitis remains controversial. Practitioners continue to treat infants with a variety of pharmacologic agents, despite limited evidence of their efficacy. Investigators continue to search for the safest and most cost-effective methods to treat infants with bronchiolitis, not only to overcome obstructive symptoms during the acute illness, but also to prevent recurrent symptoms of airway obstruction that occur in some children for years after their initial episode of bronchiolitis. Improved understanding of the pathogenesis of RSV infection and of virus-host interactions may one day lead to the development of agents that alter the initial inflammatory response and strategies that help prevent recurrent episodes of wheezing and the development of asthma after acute bronchiolitis.

Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

Airways become less compliant with age. When examined at either extreme of the developmental spectrum, airway smooth muscle (ASM) undergoes changes that parallel the trachea: both passive and active stress increase from preterm to adult. To determine how ASM changes throughout maturation, trachealis muscles from sheep airways of five age groups (group 1, <110 d gestation; group 2, 110–124 d gestation; group 3, 125–140 d gestation; group 4, newborn; and group 5, adult) were separated from their cartilaginous supports and cleaned of their mucosa and serosa. The length at which active stress was optimal was determined and passive and active stress were measured. Concentration-effect curves for acetylcholine (ACh) and KCl were performed at the length at which active stress was optimal. Morphometric analysis of the muscle was performed by computerized image analysis. At the length at which active stress was optimal, both passive and active stress increased with maturation (p < 0.001). Concentration-effect curves for both ACh and KCl also showed a significant increase in active stress as a function of dose and of age (p < 0.002), and the ED50 for ACh decreased with maturation (p < 0.005). Although muscle length, thickness, and area increased with age (p < 0.005), the ratio of contractile to connective tissue within the muscle bundle remained constant throughout maturation. These data demonstrate that ASM undergoes a progressive increase in contractility and sensitivity to ACh throughout maturation. The inability of immature ASM to generate as much force as adult ASM may in part explain why preterm infants who require positive-pressure ventilation are at risk to sustain structural central airway injury.

The Pathophysiology of Respiratory Impairment in Pediatric Neuromuscular Diseases

This is a summary of the presentation on the pathophysiology of respiratory impairment in pediatric neuromuscular disorders presented as part of the program on pulmonary management of pediatric patients with neuromuscular disease at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.

Effect of sleep stage on breathing in children with central hypoventilation.

The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean +/- SD) 13 +/- 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 +/- 23%) than NREM (drop of 87 +/- 16%, P = 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.

Airway clearance in children with neuromuscular weakness.

Purpose of review Assistance with airway clearance is critical for reducing morbidity and mortality in children with neuromuscular weakness. Several techniques and devices are available to enhance airway clearance in patients with neuromuscular disease. Only recently, however, has assessment of their effectiveness included children. This review highlights the rationale for use of both secretion extraction and mucus mobilization techniques and devices, emphasizing findings in pediatric patients whenever possible. Recent findings Cough in adults is adequate when peak cough flow exceeds 160 l/min. Similar threshold values in young children have not been established. Those methods that enhance secretion extraction include breath stacking, manual or mechanical insufflation, manually assisted cough, and mechanical insufflation–exsufflation. All are well tolerated in children and can increase peak cough flows, although the greatest increase occurs with mechanical insufflation–exsufflation. Techniques successfully used to help mobilize secretions include high frequency chest wall oscillation and intrapulmonary percussive ventilation. Various modalities can be used successfully alone or in combination. Summary Secretion extraction and mobilization techniques are safe, even in infants who require airway clearance assistance. To date, however, criteria specific for children are lacking to determine when such modalities should be used and which ones are most effective.

Barriers to adherence to cystic fibrosis infection control guidelines

In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence‐based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients.

Pulmonary function in hospitalized infants and toddlers with cystic fibrosis.

UNLABELLED In older children with cystic fibrosis (CF), well-documented improvements in lung function occur during hospitalization for treatment of pulmonary exacerbations. OBJECTIVES (1) To test the hypothesis that improvement in lung function occurs in infants and toddlers hospitalized because of CF pulmonary exacerbations. (2) To compare changes in lung function measured during forced expiratory flow and tidal breathing. STUDY DESIGN Seventeen infants and toddlers with CF were evaluated at the beginning and end of hospitalization by the rapid thoracic compression technique to yield maximal flow at forced residual capacity. Tidal mechanics were measured by the esophageal balloon technique to yield lung conductance and compliance. RESULTS Lung function improved during the course of hospitalization. The greatest change was observed in measurements of maximal flow at functional residual capacity (.VmaxFRC), increasing from 38.5% +/- 6% predicted (mean +/- SEM) to 59.8% +/- 6% at the end (p < 0.005). Lung conductance (GL) increased from 60% +/- 6% to 78% +/- 8% (p < 0.02); lung compliance (CL) increased from 66% +/- 5% to 75% +/- 5% (p < 0.03). The degree of improvement of .VmaxFRC, GL, and CL was related to baseline measurements; those with poorer pulmonary function at baseline had the greatest degree of improvement during hospitalization. CONCLUSION Assessments of airflow obstruction from measurements of .VmaxFRC and GL do not necessarily demonstrate similar findings in a given infant with CF, perhaps because these two techniques measure different physiologic properties. Changes in .VmaxFRC may best reflect the predominant pathophysiology of lung disease in infants and toddlers with CF.

Airway structure, function and development in health and disease.

Until they are fully mature, the airways are highly susceptible to damage. Factors that may contribute to vulnerability of immature airways and the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates include decreased contractility of smooth muscles of the airway, which leads to generation of lower forces, and immaturity of airway cartilage, leading to increased compressibility of developing airways. Mechanical ventilation has little effect on adult airways, but affects the dimensions and mechanical properties of preterm and newborn airways. Techniques for clinical evaluation of airway function include: (i) measurements of airway function during tidal breathing (airway resistance and reactivity are significantly elevated in infants with BPD); (ii) forced expiratory flow measurements [small‐airway obstruction in infants with BPD is indicated by markedly reduced maximal volume measurements (Vmax)]; (iii) radiography procedures (plain radiographs, fluoroscopy, computed tomography and virtual bronchoscopy); and (iv) endoscopy procedures (rigid or flexible bronchoscopy, with or without measurement of oesophageal pressure). Imaging has demonstrated an excessively decreased airway cross‐sectional area during exhalation in infants with BPD and acquired tracheomegaly in very preterm infants who had received mechanical ventilatory support. To further advance our understanding of how the airways develop, and to design less damaging protocols for mechanical ventilation in preterm neonates, basic laboratory studies of airway ultrastructure need to be performed and the results correlated with clinical pulmonary function studies.

Quantitative Bronchoscopic Assessment of Airway Collapsibility in Newborn Lamb Tracheae

To date, quantitative studies of the inherent characteristics of the developing airway wall have required excision of an airway segment or surgical creation of an isolated segment. We hypothesized that airway wall characteristics, at various collapsing pressures, and attendant changes in stiffness after smooth muscle stimulation could be quantitated bronchoscopically from airway pressure-area relationships. Neonatal lamb tracheal segments (n = 12) were suspended over hollow mounts, in a buffer-filled chamber, and subjected to a range (0 to -4.0 kPa) of pressures to determine wall stiffness under collapsing forces before and after stimulation of the trachealis with methacholine. Luminal images were recorded through a 3.6-mm flexible bronchoscope under the same conditions, subsequently corrected for distortion, and a cross-sectional area was quantitated. Both pressure-volume and pressure-area relationships detected significant changes in airway wall stiffness after methacholine administration (p < 0.002), and the magnitude of change was similar between methods. These data suggest that quantitative flexible bronchoscopy can be used clinically in the intact airway to assess wall stiffness.

Lung function over the first 3 years of life in children with congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have variable degrees of pulmonary hypoplasia at birth. Few reports of lung function over the first years of life exist in this group of children.