How does the Canadian Acute Respiratory Illness and Flu Scale relate to other scales in pediatric asthma exacerbations?

OBJECTIVES: In children with asthma exacerbations, we evaluated the relationship between Canadian Acute Respiratory Illness and Flu Scale (CARIFS) scores and (a) Asthma Diary Scale (ADS) scores for 14 days; (b) Pediatric Asthma Caregiver's Quality of Life (QoL) Questionnaire (PACQLQ) scores on days 1, 7 and 14; (c) viral detection. We hypothesized that in children with acute asthma, CARIFS scores correlate with ADS and PACQLQ scores over time and that viruses have little impact on CARIFS scores. METHODS: In children aged 2-16 years who presented with acute asthma to the Emergency Departments of 2 hospitals, we documented the clinical history, examination, asthma severity at baseline and on presentation. Eighteen respiratory pathogens were determined by PCR on nasopharyngeal aspirate (NPA) collected on recruitment. The parent(s) recorded their child's daily CARIFS and ADS and weekly PACQLQ for 14 days. We used Spearman's correlation to relate the scores of 108 children. RESULTS: CARIFS scores correlated well with ADS scores throughout 14 days (rs ranged 0.30-0.67). CARIFS and PACQLQ scores correlated -0.28, -0.14 and -0.44 on days 1, 7 and 14 respectively. There was no significant difference in CARIFS scores between children whose NPAs were PCR virus-positive or -negative over 14 days. CONCLUSIONS: CARIFS and ADS scores correlated well as a disease severity measure during the recovery period in children with acute asthma and this was not influenced by the virus state. The ADS may be used as an alternative in selected situations. The CARIFS reflects different aspects to acute asthma severity and QoL.

Determinants of cough and caregivers' quality of life in pediatric asthma exacerbations.

OBJECTIVES: In hospitalized and nonhospitalized children with asthma exacerbations, we evaluated the determinants of (a) prolonged cough on day-14 and (b) asthma quality of life (QoL) questionnaires for parents (PACQLQ) on day-21. We hypothesized that children with more severe acute asthma are more likely to have prolonged cough and/or poorer PACQLQ during the recovery phase. DESIGN: Prospective cohort study performed during 2009-2011. METHODOLOGY: Two hundred and forty-four children aged 2-16 years presenting with acute asthma to the Emergency Departments of two hospitals were recruited. Clinical history, examination, baseline asthma severity, and acute asthma severity on presentation were documented. Validated daily cough diaries and weekly PACQLQ were recorded for 14 and 21 days, respectively. RESULTS: 34.4% and 32.2% of children who returned the daytime and nighttime cough diaries respectively had a prolonged cough. Those on regular inhaled corticosteroids (ICS) were significantly more likely to have a daytime or nighttime cough score of ≥1 on day-14 (odds ratio [ORadjusted ] = 4.70, 95% confidence interval [CI] 1.65, 13.35, p = .004 and ORadjusted = 2.65, 95% CI 1.05, 6.69, p = .040, respectively). PACQLQ on day-21 was significantly poorer in younger children (mean difference [MD] = -0.04 per year, 95% CI -0.08, -0.01, p = .016), those on ICS (MD = -0.31, 95% CI -0.52, -0.09, p = .005), leukotriene antagonists (MD = -0.42, 95% CI -0.83, -0.02, p = .040) and in those who had an unplanned visit for asthma on day-21 (MD = -1.20, 95% CI -1.61, -0.78, p = .0001). CONCLUSIONS: Post an acute asthma exacerbation, children on regular ICS were more likely to have prolonged cough and poorer QoL. While this may be reflective of asthma severity or control, its association deserves further evaluation.

Presence of atopy increases the risk of asthma relapse.

OBJECTIVES: To describe the point prevalence of respiratory viruses/atypical bacteria using PCR and evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery in children with hospitalised and non-hospitalised asthma exacerbations. DESIGN: This was a prospective study performed during 2009-2011. SETTING: The study was performed in the emergency departments of two hospitals. PATIENTS: 244 children aged 2-16 years presenting with acute asthma to the emergency departments were recruited. A nasopharyngeal aspirate and allergen skin prick test were performed. MAIN OUTCOME MEASURES: The outcomes were divided into (1) acute severity outcomes (Australian National Asthma Council assessment, hospitalisation, Functional Severity Scale, Acute Asthma Score, asthma quality of life questionnaires for parents (PACQLQ) on presentation, asthma diary scores (ADS) on presentation and length of hospitalisation) and (2) recovery outcomes (PACQLQ for 21 days, ADS for 14 days and representation for asthma for 21 days). RESULTS: PCR for viruses/atypical bacteria was positive in 81.7% of children (75.1% human rhinovirus, codetection in 14.2%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were rarely detected. The presence of micro-organisms had little impact on acute asthma or recovery outcomes. Children with atopy were significantly more likely to relapse and represent for medical care by day 14 (OR 1.11, 95% CI 1.00 to 1.23). CONCLUSIONS: The presence of any viruses is associated with asthma exacerbations but does not appear to influence asthma recovery. In contrast, atopy is associated with asthma relapse. M. pneumoniae and C. pneumoniae are rare triggers of acute asthma in young children.

Children with chronic cough: when is watchful waiting appropriate? development of likelihood ratios for assessing children with chronic cough.

BACKGROUND: Chronic cough is associated with poor quality of life and may signify a serious underlying disease. Differentiating nonspecific cough (when watchful waiting can be safely undertaken) from specific cough (treatment and further investigations are beneficial) would be clinically useful. In 326 children, we aimed to (1) determine how well cough pointers (used in guidelines) differentiate specific from nonspecific cough and (2) describe the clinical profile of children whose cough resolved without medications (spontaneous resolution). METHODS: A dataset from a multicenter study involving children newly referred for chronic cough (median duration, 3-4 months) was used to determine the sensitivity, specificity, predictive values, and likelihood ratios (LRs) of cough pointers (symptoms, signs, and simple investigations [chest radiography, spirometry]) recommended in guidelines. RESULTS: The pretest probability of specific cough was 88%. The absence of false-positive results meant that most pointers had strongly positive LRs. The most sensitive pointer (wet cough) had a positive LR of 26.2 (95% CI, 3.8-181.5). Although the absence of other individual pointers did not change the pretest probability much (negative LR close to 1), the absence of all pointers had a strongly negative LR of 0 (95% CI, 0-0.03). Children in the resolved spontaneously group were significantly more likely to be older, to be non-Indigenous, and to have a dry cough and a normal chest radiograph. CONCLUSIONS: Children with chronic dry cough without any cough pointers can be safely managed using the watchful waiting approach. The high pretest probability and high positive LRs of cough pointers support the use of individual cough pointers to identify high risk of specific cough in pediatric chronic cough guidelines. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: 12607000526471; URL: www.anzctr.org.au.

A cough algorithm for chronic cough in children: a multicenter, randomized controlled study.

OBJECTIVES: The goals of this study were to: (1) determine if management according to a standardized clinical management pathway/algorithm (compared with usual treatment) improves clinical outcomes by 6 weeks; and (2) assess the reliability and validity of a standardized clinical management pathway for chronic cough in children. METHODS: A total of 272 children (mean ± SD age: 4.5 ± 3.7 years) were enrolled in a pragmatic, multicenter, randomized controlled trial in 5 Australian centers. Children were randomly allocated to 1 of 2 arms: (1) early review and use of cough algorithm ("early-arm"); or (2) usual care until review and use of cough algorithm ("delayed-arm"). The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6. Secondary measures included cough duration postrandomization and the algorithm's reliability, validity, and feasibility. RESULTS: Cough resolution (at week 6) was significantly more likely in the early-arm group compared with the delayed-arm group (absolute risk reduction: 24.7% [95% confidence interval: 13-35]). The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group (mean difference between groups: 0.6 [95% confidence interval: 0.29-1.0]). Duration of cough postrandomization was significantly shorter in the early-arm group than in the delayed-arm group (P = .001). The cough algorithm was reliable (κ = 1 in key steps). Feasibility was demonstrated by the algorithm's validity (93%-100%) and efficacy (99.6%). Eighty-five percent of children had etiologies easily diagnosed in primary care. CONCLUSIONS: Management of children with chronic cough, in accordance with a standardized algorithm, improves clinical outcomes irrespective of when it is implemented. Further testing of this standardized clinical algorithm in different settings is recommended.

Anticholinergic therapy for acute asthma in children.

BACKGROUND: Inhaled anticholinergics as single agent bronchodilators (or in combination with beta(2)-agonists) are one of the several medications available for the treatment of acute asthma in children. OBJECTIVES: To determine the effectiveness of only inhaled anticholinergic drugs (i.e. administered alone), compared to a control in children over the age of two years with acute asthma. SEARCH METHODS: The Cochrane Register of Controlled Trials (CENTRAL), and the Cochrane Airways Group Register of trials were searched by the Cochrane Airways Group. The latest search was performed in April 2011. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in which inhaled anticholinergics were given as single therapy and compared with placebo or any other drug or drug combinations for children over the age of two years with acute asthma. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data and assessed trial quality. MAIN RESULTS: Six studies met the inclusion criteria but were limited by small sample sizes, various treatment regimes used and outcomes assessed. The studies were overall of unclear quality. Data could only be pooled for the outcomes of treatment failure and hospitalisation. Other data could not be combined due to divergent outcome measurements. Meta-analysis revealed that children who received anticholinergics alone were significantly more likely to have treatment failure compared to those who received beta(2)-agonists from four trials on 171 children (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). Also, treatment failure on anticholinergics alone was more likely than when anticholinergics were combined with beta(2)-agonists from four trials on 173 children (OR 2.65; 95% CI 1.2 to 5.88). Data on clinical scores/symptoms that were measured on different scales were conflicting. Individual trials reported that lung function was superior in the combination group when compared with anticholinergic agents used alone. The use of anticholinergics was not found to be associated with significant side effects. AUTHORS' CONCLUSIONS: In children over the age of two years with acute asthma exacerbations, inhaled anticholinergics as single agent bronchodilators were less efficacious than beta(2)-agonists. Inhaled anticholinergics were also less efficacious than inhaled anticholinergics combined with beta(2)-agonists. Inhaled anticholinergic drugs alone are not appropriate for use as a single agent in children with acute asthma exacerbations.

A multicenter study on chronic cough in children : burden and etiologies based on a standardized management pathway.

BACKGROUND: While the burden of chronic cough in children has been documented, etiologic factors across multiple settings and age have not been described. In children with chronic cough, we aimed (1) to evaluate the burden and etiologies using a standard management pathway in various settings, and (2) to determine the influence of age and setting on disease burden and etiologies and etiology on disease burden. We hypothesized that the etiology, but not the burden, of chronic cough in children is dependent on the clinical setting and age. METHODS: From five major hospitals and three rural-remote clinics, 346 children (mean age 4.5 years) newly referred with chronic cough (> 4 weeks) were prospectively managed in accordance with an evidence-based cough algorithm. We used a priori definitions, timeframes, and validated outcome measures (parent-proxy cough-specific quality of life [PC-QOL], a generic QOL [pediatric quality of life (PedsQL)], and cough diary). RESULTS: The burden of chronic cough (PC-QOL, cough duration) significantly differed between settings (P = .014, 0.021, respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did not correlate with age. The frequency of etiologies was significantly different in dissimilar settings (P = .0001); 17.6% of children had a serious underlying diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted bacterial bronchitis, the frequency of other common diagnoses (asthma, bronchiectasis, resolved without specific-diagnosis) was similar across age categories. CONCLUSIONS: The high burden of cough is independent of children's age and etiology but dependent on clinical setting. Irrespective of setting and age, children with chronic cough should be carefully evaluated and child-specific evidence-based algorithms used.

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.

Treatment of obstructive sleep apnoea for chronic cough in children.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is a disorder that is characterised by repeated episodes of partial or complete upper airway obstruction (UAO) during sleep that result in disruption of normal ventilation and sleep patterns. Chronic cough in children is a significant medical problem and in some situations warrants thorough investigation. There may be an association between chronic cough and OSA as suggested in adult studies. OBJECTIVES: To evaluate the efficacy of treatment of OSA leading to the resolution of cough in the management of children with chronic cough. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE and EMBASE. The latest search was performed in September 2010. SELECTION CRITERIA: All randomised controlled trials comparing an intervention for OSA to a control group (placebo or usual treatment) in children with chronic cough. DATA COLLECTION AND ANALYSIS: We reviewed the search results against the pre-determined criteria for inclusion. Two review authors independently selected the studies. No eligible trials were identified and thus no data were available for analysis. MAIN RESULTS: We found no randomised controlled trials that examined the efficacy of treatment of OSA in the management of children with chronic cough. AUTHORS' CONCLUSIONS: There is currently no evidence that therapies directed for OSA are useful for the management of chronic cough in children. Until further evidence is available, OSA should be managed on its own merits and the presence or absence of cough should not be used as a decision trigger. Further research examining the effects of this intervention is needed.

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.

Rapid eye movement latency in children and adolescents.

Rapid eye movement sleep distribution changes during development, but little is known about rapid eye movement latency variation in childhood by age, sex, or pathologic sleep states. We hypothesized that: (1) rapid eye movement latency would differ in normal children by age, with a younger cohort (1-10 years) demonstrating shorter rapid eye movement latency than an older group (>10-18 years); (2) rapid eye movement latency in children would differ from typical adult rapid eye movement latency; and (3) intrinsic sleep disorders (narcolepsy, pediatric obstructive sleep apnea syndrome) would disrupt normal developmental patterns of rapid eye movement latency. A retrospective chart review included data from clinic visits and of rapid eye movement latency and other parameters measured by overnight polysomnography. Participants included 98 control children, 90 children with obstructive sleep apnea syndrome, and 13 children with narcolepsy. There were no statistically significant main effects of age category or sex on rapid eye movement latency. Rapid eye movement latency, however, exhibited a significant inverse correlation with age within the older control children. Healthy children exhibited rapid eye movement latencies significantly longer than adults. Normal control patients demonstrated significantly longer rapid eye movement latency than obstructive sleep apnea syndrome and narcolepsy patients.

Acute asthma in children: Relationships among CD14 and CC16 genotypes, plasma levels, and severity.

RATIONALE: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism. OBJECTIVES: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity. METHODS: We studied 148 children on presentation with acute asthma and again in convalescence. CD14 C-159T and CC16 A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times. MEASUREMENTS AND MAIN RESULTS: During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 -159TT (p = 0.003) and -159CT (p = 0.004), and not in those with -159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 -159CC and CC16 38AA were more likely to have moderate or severe acute asthma. CONCLUSIONS: Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 -159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.