Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care.

OBJECTIVES: To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. METHODS: Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. RESULTS: Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. CONCLUSION: This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned.

Long-term follow-up after two years of asthma treatment guided by airway responsiveness in children.

INTRODUCTION: Children with persistent asthma may have diminished lung function in early adulthood. In our previous study ('CATO') we showed preservation of lung function in asthmatic children, during 2 years of treatment that was guided by airway hyperresponsiveness (AHR). The aim of the present prospective follow up study was to investigate whether the positive effect of the AHR strategy on lung function had persisted beyond the duration of the intervention study, after several years of usual care by paediatrician and general practitioner. METHODS: With a mean interval of 4.4 y after the last visit, 137 subjects (67% of the original CATO population) participated in this follow-up study. Evaluation consisted of spirometry (n = 137), a methacholine challenge test (n = 83), data on inhaled steroid treatment and asthma exacerbations (n = 137), and an asthma symptom diary during 6 weeks (n = 90). RESULTS: At follow-up, lung function, % symptom-free days and exacerbation rates of both treatment strategy groups was similar. The mean dose of inhaled corticosteroids had diminished from 550 µg/day at the end of CATO to 235 µg/day at follow-up. The decrease in AHR measured at the end of CATO was maintained at follow-up for both treatment strategy groups. CONCLUSION: The beneficial effect on lung function of 2 years treatment guided by AHR was lost after 3-7 years of usual care. This suggests that an AHR-guided treatment strategy may need to be sustained in order to preserve lung function.

Nurse versus physician-led care for the management of asthma.

BACKGROUND: Asthma is the most common chronic disease in childhood and prevalence is also high in adulthood, thereby placing a considerable burden on healthcare resources. Therefore, effective asthma management is important to reduce morbidity and to optimise utilisation of healthcare facilities. OBJECTIVES: To review the effectiveness of nurse-led asthma care provided by a specialised asthma nurse, a nurse practitioner, a physician assistant or an otherwise specifically trained nursing professional, working relatively independently from a physician, compared to traditional care provided by a physician. Our scope included all outpatient care for asthma, both in primary care and in hospital settings. SEARCH METHODS: We carried out a comprehensive search of databases including The Cochrane Library, MEDLINE and EMBASE to identify trials up to August 2012. Bibliographies of relevant papers were searched, and handsearching of relevant publications was undertaken to identify additional trials. SELECTION CRITERIA: Randomised controlled trials comparing nurse-led care versus physician-led care in asthma for the same aspect of asthma care. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Five studies on 588 adults and children were included concerning nurse-led care versus physician-led care. One study included 154 patients with uncontrolled asthma, while the other four studies including 434 patients with controlled or partly controlled asthma. The studies were of good methodological quality (although it is not possible to blind people giving or receiving the intervention to which group they are in). There was no statistically significant difference in the number of asthma exacerbations and asthma severity after treatment (duration of follow-up from six months to two years). Only one study had healthcare costs as an outcome parameter, no statistical differences were found. Although not a primary outcome, quality of life is a patient-important outcome and in the three trials on 380 subjects that reported on this outcome, there was no statistically significant difference (standardised mean difference (SMD) -0.03; 95% confidence interval (CI) -0.23 to 0.17). AUTHORS' CONCLUSIONS: We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care costs.

Risk factors for pediatric intensive care admission in children with acute asthma.

INTRODUCTION: Severe acute asthma in children is associated with substantial morbidity and may require pediatric ICU (PICU) admission. The aim of the study was to determine risk factors for PICU admission. METHODS: The study used a retrospective multicenter case-control design. The cases included children admitted to the PICU because of severe acute asthma and a history of out-patient treatment by pediatricians or pediatric pulmonologists. Controls were children with asthma without a PICU admission for severe acute asthma. The children were matched for sex, age, hospital, and time elapsed since the diagnosis of asthma. Fourteen possible risk factors were analyzed. RESULTS: Sixty-six cases were matched to 164 controls. In univariate analysis, all but one of the analyzed variables were significantly associated with PICU-hospitalization. After multivariate conditional logistic regression analysis, 4 risk factors remained significant. These included active or passive smoking, allergies, earlier hospitalization for asthma, and non-sanitized home. CONCLUSIONS: Physicians and parents should be aware of these risk factors, and efforts should be made to counteract them.

Evaluation of interrupter resistance in methacholine challenge testing in children.

Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed using bronchial provocation tests. The primary outcome in such tests (a 20% decrease in forced expiratory volume in 1 sec (FEV1)) is difficult to measure in young patients. This study evaluated the sensitivity and specificity of the interrupter resistance (Rint ) technique, which does not require active patient participation, by comparing it to the primary outcome measure. Methacholine challenge tests were performed in children with a history of moderate asthma and BHR. Mean and individual changes in Rint and FEV1 were studied. A receiver operating characteristic (ROC) curve was used to describe sensitivity and specificity of Rint . Seventy-three children (median age: 9.2 years; range: 6.3-13.4 years) participated. There was a significant (P < 0.01) increase in mean Rint with increasing methacholine doses. However, individual changes of Rint showed large fluctuations. There was great overlap in change of Rint between children who did and did not reach the FEV1 endpoint. A ROC curve showed an area under the curve of 0.65. Because of low sensitivity and specificity, the use of Rint to diagnose BHR in individual patients seems limited.

Recombinant human DNase in children with airway malacia and lower respiratory tract infection.

BACKGROUND: Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of respiratory symptoms in children with airway malacia and lower respiratory tract infection (LRTI). METHODS: In a randomized double-blind controlled clinical trial, 40 children with airway malacia and LRTI were randomly assigned to receive either 2.5 mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline to the second week of treatment. Secondary endpoints were VAS symptom scores for cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic course, and lung function data (FVC, FEV(1), FEF(75), R(int(e))). RESULTS: There was no significant difference in the mean change in CDSs from baseline between the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of patients requiring antibiotics, and the mean changes in symptom scores and lung function from baseline did not significantly differ between both groups. CONCLUSION: Treatment with 2 weeks of nebulized rhDNase does not enhance recovery or reduce the need for antibiotics in children with airway malacia and LRTI. (Controlled-trials.com number, ISRCTN85366144).

Fluticasone or montelukast for preschool children with asthma-like symptoms: Randomized controlled trial.

RATIONALE: Beneficial effects of anti-inflammatory therapy such as fluticasone propionate (FP) and montelukast (Mk) have been demonstrated in preschool children with asthma. However, comparative studies are lacking in this age group. Therefore, we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms. METHODS: In this multicenter, randomized, placebo-controlled, double-blind, double-dummy trial, children aged 2-6 years with asthma-like symptoms were included. In total, 63 children were randomly allocated to receive FP (25), Mk (18) or placebo (20) for 3 months. The primary outcome was the daily symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card. Secondary endpoints were rescue medication free days, blood eosinophils and lung function (interrupter technique and forced oscillation technique (FOT)). RESULTS: During the 3 months study period, symptoms improved in all 3 groups, with a statistically significant difference between FP and placebo in favor of the FP group (p=0.021). A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only (p=0.008), which was significantly different from the change found in the placebo group (p=0.045). With the exception of frequency dependence (measured by FOT), which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group (p=0.048), no differences in lung function within or between groups were found. CONCLUSIONS: In spite of a lack of power, our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo. Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group, this study revealed no differences between FP and Mk.

Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase). METHODS: In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions. RESULTS: There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions. CONCLUSIONS: Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.

Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants.

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.