Clinical and lung function outcomes in a cohort of children with severe asthma.

BACKGROUND: Uncontrolled severe asthma in children is burdensome and challenging to manage. This study aims to describe outcomes in children with uncontrolled severe asthma managed in a nurse-led severe asthma clinic (SAC). METHODS: This retrospective analysis uses data collected from children referred by a paediatric respiratory specialist to a nurse-led SAC for uncontrolled severe asthma between 2014 and 2019. The pre-clinical assessments included a home visit to assess modifiable factors that could be addressed to improve control. A comprehensive lung function analysis was conducted at each visit. Interventions were personalised and included biologic agents. Statistical analysis was performed using nonparametric, two-tailed Mann-Whitney U-test, the parametric Student's t-test, or analysis of variance (ANOVA) as appropriate. RESULTS: Twenty-three children with a median age of 12 years were seen once, and 16 were followed up. Compared to a non-asthmatic (NA) and asthmatic (A) age-matched cohort, children with severe asthma (SA) had a lower FEV1, and FVC% predicted before and after bronchodilator inhalation, and a higher mean Lung Clearance Index [LCI] (10.5 [SA] versus 7.3 [NA] versus 7.6 [A], p = 0.003). Almost 80% of children with SA had an abnormal LCI, and 48% had a reduced FEV1% at the first SAC visit. Asthma control and FEV1% predicted significantly improved at a follow-up visit, while LCI remained abnormal in the majority of children (83%). CONCLUSION: Over time, many children with severe asthma showed improved clinical outcomes and lung function while lung ventilation inhomogeneities persisted. Future appropriately controlled studies are required to determine if a nurse-led multidisciplinary SAC is associated with better outcomes.

Polysomnography for the management of oxygen supplementation therapy in infants with chronic lung disease of prematurity.

Aim: Some infants with bronchopulmonary dysplasia (BPD) may require oxygen supplementation at home but a role for overnight polysomnography (PSG) in the management of home oxygen therapy has been rarely described. Methods: Forty-one infants with BPD born at less than 30 weeks gestational age were discharged with continuous home oxygen supplementation therapy between 2010 and 2013. PSG data were recorded on oxygen supplementation versus room air at median corrected age of 2 months (range 1-5 months) (first PSG after discharge to home). Those infants who continued oxygen supplementation therapy at home had at least one more PSG before oxygen therapy was discontinued (last PSG). We also collected PSG data in 10 healthy term infants (median age 3.5 months; range 2-4 months). Results: In infants with BPD in room air, increased numbers of central apneas, hypopneas, and SaO2 desaturations were the predominant PSG features with a median apnea-hypopnea index (AHI) of 16.8 events per hour (range 0-155). On oxygen supplementation therapy, median AHI dramatically improved (2.2, range 0-22; p < .001) and was not different from control infants (2.0, range 0-3.9; p = .31). AHI on room air at the last PSG when home oxygen was ceased was 4.1 per hour (range 0-13.8) slightly higher than in healthy infants. Conclusion: Central sleep disordered breathing in infants with BPD dramatically normalizes with low flow nasal cannula home oxygen therapy and improves with age. Mild central sleep disordered breathing remains detectable, although much improved, when compared with healthy infants at the time when the decision to cease home oxygen therapy was made by the physician.

Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children.

BACKGROUND AND OBJECTIVE: National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture-negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance. METHODS: Pleural fluid (PF) from children with empyema were cultured and tested by PCR to identify SP, targeting the autolysin gene (lytA). Multiplex PCR-based reverse line blot assay was used to identify SP STs. Corresponding IPD surveillance and serotype data were obtained from the National Notifiable Diseases Surveillance System (NNDSS). RESULTS: Eighty-nine children with empyema, aged ≤16 years, were recruited between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF cultures and by PCR in 43/79 (54.4%) PF samples. Serotypes were unidentifiable in 15 samples. The frequency of six serotypes (or serotype pairs) identified in 28 samples, including one with two serotypes, were: ST1, n = 4/29 (13.8%); ST3, n = 9/29 (31.0%); ST19A, n = 12/29 (41.4%); ST7F/7A, n = 1/29 (3.4%); ST9V/9A, n = 1/29 (3.4%); ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients, aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly lower than in PF samples: ST1, n = 8/331 (2.4%; P < 0.05); ST3, n = 13/331 (3.9%; P < 0.0001). CONCLUSIONS: The use of PCR to identify and serotype SP in culture-negative specimens provides additive information.

Bacterial causes of empyema in children, Australia, 2007-2009.

An increase in the incidence of empyema worldwide could be related to invasive pneumococcal disease caused by emergent nonvaccine replacement serotypes. To determine bacterial pathogens and pneumococcal serotypes that cause empyema in children in Australia, we conducted a 2-year study of 174 children with empyema. Blood and pleural fluid samples were cultured, and pleural fluid was tested by PCR. Thirty-two (21.0%) of 152 blood and 53 (33.1%) of 160 pleural fluid cultures were positive for bacteria; Streptococcus pneumoniae was the most common organism identified. PCR identified S. pneumoniae in 74 (51.7%) and other bacteria in 19 (13.1%) of 145 pleural fluid specimens. Of 53 samples in which S. pneumoniae serotypes were identified, 2 (3.8%) had vaccine-related and 51 (96.2%) had nonvaccine serotypes; 19A (n = 20; 36.4%), 3 (n = 18; 32.7%), and 1 (n = 8; 14.5%) were the most common. High proportions of nonvaccine serotypes suggest the need to broaden vaccine coverage.

A bedside assay to detect streptococcus pneumoniae in children with empyema.

BACKGROUND: Empyema is a complication of pneumonia, commonly caused by Streptococcus pneumoniae. AIMS: To validate the utility of an immunochromatographic test for the detection of S. pneumoniae antigen in the pleural fluid of children with empyema. METHODS: Empyema patients had blood and pleural fluid cultured, and polymerase chain reaction (PCR) to detect the S. pneumoniae autolysin gene, lytA, in pleural fluid. Pleural fluid was tested using the Binax NOW S. pneumoniae antigen detection assay and compared with lytA PCR results and/or culture in blood or pleural fluid. RESULTS: S. pneumoniae was detected by PCR in pleural fluid of 68 of 137 (49.6%) patients, by culture in 11 of 135 (8.1%) pleural specimens and 16 of 120 (13.3%) blood specimens. Pleural fluid Binax NOW testing from 130 patients demonstrated a sensitivity of 83.8% and specificity of 93.5% (positive predictive value of 93.4% and negative predictive value of 84.1%). CONCLUSIONS: In pediatric empyema, high predictive values of pleural fluid Binax NOW S. pneumoniae antigen test suggest that this test may help rationalize antibiotic choice in these patients.

Polysomnographic outcome of adenotonsillectomy for obstructive sleep apnea in children under 5 years old.

OBJECTIVE: To determine success rates after adenotonsillectomy for obstructive sleep apnea (OSA); postoperative polysomnogram (PSG) results were compared with preoperative results in children younger than 5 years. METHODS: Thirty-four children with a preoperative respiratory disturbance index (RDI) greater than 5 in rapid eye movement (REM) sleep underwent both preoperative and postoperative PSG with at least five of seven parameters recorded. RESULTS: Preoperatively, mean total RDI was 15.5, mean REM RDI was 39.6, and 25 (74%) had severe OSA (REM RDI > 20). Postoperatively, mean total RDI improved to 3 (P < 0.001), mean REM RDI to 7.4 (P < 0.001), and 4 remained severe. Overall 22 (65%) showed REM RDI in the normal range (<5), including all with a preoperative REM RDI less than 30. CONCLUSION: On PSG criteria, most children with OSA significantly improved after adenotonsillectomy, but a number had persisting abnormalities. Postoperative PSG should be considered to identify unresolved OSA.

Inhaled corticosteroids in children with asthma: pharmacologic determinants of safety and efficacy and other clinical considerations.

The role of inhaled corticosteroids (ICS) in the treatment of childhood asthma has been well established. An ideal corticosteroid should demonstrate high pulmonary deposition and residency time, in addition to a low systemic bioavailability and rapid systemic clearance. The lung depositions of the ICS have been compared, with beclomethasone (beclometasone)-hydrofluoroalkane (HFA) and ciclesonide showing the highest lung deposition. Lung deposition is influenced by not only the inhalation device and type of propellant (HFA or chlorofluorocarbon), but also by whether the aerosol is a solution or suspension, and the particle size of the respirable fraction. Pulmonary residency time increases when budesonide and des-ciclesonide undergo reversible fatty acid esterification. The bioavailability of the drug depends on the oral bioavailable fraction and the amount absorbed directly from the pulmonary vasculature. The clearance rate of des-ciclesonide is very high (228 L/h), increasing its safety profile by utilizing extra-hepatic clearance mechanisms. Both des-ciclesonide and mometasone have a high protein binding fraction (98-99%). The volume of distribution (Vd) is proportional to the lipophilicity of the drug, with the Vd of fluticasone being 332L compared with 183L for budesonide. Increasing the Vd will also increase the elimination half-life of a drug. The pharmacodynamics of ICS depend on both the receptor binding affinity and the dose-response curve. Among the ICS, fluticasone and mometasone have the highest receptor binding affinity (1800 and 2200, respectively), followed by budesonide at 935 (relative to dexamethasone = 100). Compared with other nonsteroid asthma medications (long-acting beta-agonists, theophylline, and montelukast) ICS have proven superiority in improving lung function, symptom-free days, and inflammatory markers. One study suggests that early intervention with ICS reduces the loss in lung function (forced expiratory volume in 1 second) over 3 years. Whether airway remodeling is reduced or prevented in the long term is unknown. Potential adverse drug effects of ICS include adrenal and growth suppression. While in low-to-medium doses ICS have shown little suppression of the adrenal pituitary axis, in high doses the potential for significant adrenal suppression and adrenal crisis exists. Several longitudinal studies evaluating the effect of ICS on growth have shown a small decrement in growth velocity (approximate 1-2 cm) during the first year of treatment. However, when investigators followed children treated with budesonide for up to 10 years, no change in target adult height was noted. In conclusion, the development of optimal delivery devices for young children, as well as optimizing favorable pharmacokinetic properties of ICS should be priorities for future childhood asthma management.

Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy.

OBJECTIVE: To investigate the relative contribution of various risk factors to the surgical outcome of adenotonsillectomy for obstructive sleep apnea syndrome in children. STUDY DESIGN: Children (n = 110; mean age, 6.4 +/- 3.9 years) underwent two polysomnographic evaluations before and after adenotonsillectomy. In addition, 22 control children were studied. History for allergy and family history of sleep-disordered breathing was taken before each polysomnographic evaluation. RESULTS: Significant changes in sleep stage percentages and sleep fragmentation were found in the postsurgery study compared with the presurgery study; 25% of the children had apnea/hypopnea index (AHI) 1 and <5, and 29% had AHI >/=5 in the postsurgery study. The frequency of subjects with AHI

Polysomnographic characteristics in normal preschool and early school-aged children.

OBJECTIVE: The objective of this study was to describe overnight polysomnographic measures in normal children aged 3 to 7 years. We conducted a retrospective analysis of normal polysomnographic evaluations from participants in 2 large community-based studies of sleep-disordered breathing among preschoolers and early school-aged children at Kosair Children's Hospital Sleep Medicine Research Center at the University of Louisville. Participants included 542 healthy children with ages ranging from 3.2 to 8.6 years. RESULTS: Subjects were excluded from analysis if they had documented snoring during polysomnography, an obstructive apnea-hypopnea index of > or =1.0, or a periodic leg-movement index of > or =5.0. Because the greatest differences in polysomnography occurred between ages 5 and 6 years, analyses were performed for children 3 to 5 years and for ages > or =6. Sleep cyclicity was distinct between age groups, with both showing an initial brief rapid-eye-movement period, which lengthened across the night, but only the older group showing a decrease in cycle length across the night. Average obstructive apnea indices were 0.03 per hour of total sleep time (TST) for 3- to 5-year-old children and 0.05 per hour of TST for > or =6-year-old children, whereas central apnea indices were 0.82 and 0.45 per hour of TST, respectively. Older children spent a greater percentage of sleep time supine, and the apnea-hypopnea index differed according to body position. Twenty percent of all subjects had end tidal carbon dioxide values of >45 mm Hg, and 2.2% had recorded values >50 mm Hg during > or =50% TST. High variance was present on all measures. CONCLUSIONS: Developmental changes occur in several polysomnographic measures among normal children from 3 to 7 years of age, particularly during transition from preschool to early school age. Our findings in a large number of healthy community children comprise the most extensive compilation of normative reference values for laboratory-based pediatric polysomnography to date.

Effects of glucocorticoids on the hypothalamic-pituitary-adrenal axis in children and adults.

Inhaled and intranasal corticosteroids are widely used as effective, first-line treatments for asthma and allergic rhinitis. Despite a good safety profile of these formulations, there is increasing concern about their propensity to produce systemic adverse effects. Suppression of the hypothalamic-pituitary-adrenal axis is one of the most important potential complications. This article reviews the effects of inhaled and intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis function in adults and children.