In Vivo Evidence of Respiratory Syncytial Virus Persistence in a Subset of Pulmonary Dendritic Cells Following a Primary Infection.

Respiratory syncytial virus (RSV) causes annual epidemics of infections affecting the whole population. In vitro, it has been shown to infect and persist in human dendritic cells (DCs) for prolonged periods. Initially persistence is associated with low levels of replication before the virus becomes dormant. Reactivation of viral replication can be triggered many months later. Infection of DCs is likely to influence the host's ability to generate effective long-term memory responses. A well-established animal was utilized to confirm that RSV both infects and persists in pulmonary DCs in vivo. Mice were infected with a modified strain of RSV expressing red fluorescent protein (RSV-RFP) when replicating. Clinical symptoms of infection were monitored using weight change and inflammatory cell counts from bronchoalveolar lavage, which correlated with the RSV viral titer (quantitative polymerase chain reaction). Lung tissues were collected at 3, 5, 7, and 21 days postinfection (dpi) to assess leukocyte populations by flow cytometry. Clinical symptoms and RSV viral load peaked at 5 dpi. RSV-RFP was most prevalent in macrophages at 3 dpi and also observed in B cells and DCs. At 21 dpi, RSV-RFP remained evident in a subset of conventional DCs (CD103+CD11b+) even though both clinical symptoms and pulmonary inflammation had resolved. These results confirm that in this well-established mouse model, RSV persists in lung conventional DCs following resolution of the acute infection. Further work is required to explore whether the virus continues with low-level replication before becoming dormant in vivo, as has been described in vitro.

Challenging the paradigm.

While advocating for addressing "treatable traits" is admirable in that it reminds clinicians to consider the patient and not the disease, the use of this idea to promote dangerous changes in practice should be challenged. https://bit.ly/30VkP8Q.

Controlled inhalation improves central and peripheral deposition in cystic fibrosis patients with moderate lung disease.

AIM: With progressive impairment of lung function, deposition of inhaled drug in the lungs becomes progressively more central, limiting its effectiveness. This pilot study explored the possibility that long slow inhalations might improve delivery of aerosol to the lung periphery in cystic fibrosis patients with moderate lung disease. METHODS: Five subjects aged 12-18 years (mean FEV1 72%; range 63-80%) inhaled a radiolabelled aerosol from a jet nebuliser on two occasions. Two inhalation techniques were compared: breathing tidally from a standard continuous output nebuliser and using long slow inhalations from the AKITA® JET system. RESULTS: Long slow breaths resulted in much lower oropharyngeal deposition with higher lung doses. Importantly, the peripheral lung increased proportionately. The increased lung dose is attributable to more of the larger inhaled droplets passing into the lower airways. This would be expected to increase the central deposition unless significantly more of the smaller droplets were able to penetrate deeper into the lungs. The data support improved delivery of drug to the distal lung when compared with tidal breathing. CONCLUSION: These pilot data suggest that this approach may prove to be clinically relevant in improving the efficacy of inhaled medication in those with moderate-severe lung disease.

Precision Medicine and Childhood Asthma: A Guide for the Unwary.

Many thousands of articles relating to asthma appear in medical and scientific journals each year, yet there is still no consensus as to how the condition should be defined. Some argue that the condition does not exist as an entity and that the term should be discarded. The key feature that distinguishes it from other respiratory diseases is that airway smooth muscles, which normally vary little in length, have lost their stable configuration and shorten excessively in response to a wide range of stimuli. The lungs' and airways' limited repertoire of responses results in patients with very different pathologies experiencing very similar symptoms and signs. In the absence of objective verification of airway smooth muscle (ASM) lability, over and underdiagnosis are all too common. Allergic inflammation can exacerbate symptoms but given that worldwide most asthmatics are not atopic, these are two discrete conditions. Comorbidities are common and are often responsible for symptoms attributed to asthma. Common amongst these are a chronic bacterial dysbiosis and dysfunctional breathing. For progress to be made in areas of therapy, diagnosis, monitoring and prevention, it is essential that a diagnosis of asthma is confirmed by objective tests and that all co-morbidities are accurately detailed.

Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis.

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies. Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses. Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively. Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

High levels of inherent variability in microbiological assessment of bronchoalveolar lavage samples from children with persistent bacterial bronchitis and healthy controls.

Bronchoalveolar lavage (BAL) is widely regarded as providing "gold standard" samples for infective lower respiratory tract disease. Current approaches have been adopted empirically without robust assessment and hence carry many assumptions that have not been tested. Many of these uncertainties were highlighted in the ATS pediatric bronchoscopy guidelines. This study was designed to explore some of these issues. BAL was undertaken via an endotracheal tube in 13 subjects aged less than 6 years with persistent bacterial bronchitis and five healthy controls. Aliquots of the same pooled BAL sample were sent to two accredited laboratories. one producing semiquantitative results and the other quantitative results. For five patients potentially pathogenic bacteria were grown by one laboratory but not the other, while in three more there were discrepancies in the organisms reported. Despite being symptomatic and off antibiotics, only 3 of 13 patients were reported to have a pathogen at a density of more than 1 × 104 colony forming unit. There was at best a poor correlation between semiquantitative and quantitative data. Potential pathogens were cultured in two of five control samples. The results suggest that the results from conventional microbiological assessment of BAL samples can be highly variable and that the proposal that a discrete cut-off is of value in patients with chronic endobronchial infection is probably invalid.

Time to Say Goodbye to Bronchiolitis, Viral Wheeze, Reactive Airways Disease, Wheeze Bronchitis and All That.

The diagnosis and management of infants and children with a significant viral lower respiratory tract illness remains the subject of much debate and little progress. Over the decades various terms for such illnesses have been in and fallen out of fashion or have evolved to mean different things to different clinicians. Terms such as "bronchiolitis," "reactive airways disease," "viral wheeze," and many more are used to describe the same condition and the same term is frequently used to describe illnesses caused by completely different dominant pathologies. This lack of clarity is due, in large part, to a failure to understand the basic underlying inflammatory and associated processes and, in part, due to the lack of a simple test to identify a condition such as asthma. Moreover, there is a lack of insight into the fact that the same pathology can produce different clinical signs at different ages. The consequence is that terminology and fashions in treatment have tended to go around in circles. As was noted almost 60 years ago, amongst pre-school children with a viral LRTI and airways obstruction there are those with a "viral bronchitis" and those with asthma. In the former group, a neutrophil dominated inflammation response is responsible for the airways' obstruction whilst amongst asthmatics much of the obstruction is attributable to bronchoconstriction. The airways obstruction in the former group is predominantly caused by airways secretions and to some extent mucosal oedema (a "snotty lung"). These patients benefit from good supportive care including supplemental oxygen if required (though those with a pre-existing bacterial bronchitis will also benefit from antibiotics). For those with a viral exacerbation of asthma, characterized by bronchoconstriction combined with impaired b-agonist responsiveness, standard management of an exacerbation of asthma (including the use of steroids to re-establish bronchodilator responsiveness) represents optimal treatment. The difficulty is identifying which group a particular patient falls into. A proposed simplified approach to the nomenclature used to categorize virus associated LRTIs is presented based on an understanding of the underlying pathological processes and how these contribute to the physical signs.

Asthma: A Loss of Post-natal Homeostatic Control of Airways Smooth Muscle With Regression Toward a Pre-natal State.

The defining feature of asthma is loss of normal post-natal homeostatic control of airways smooth muscle (ASM). This is the key feature that distinguishes asthma from all other forms of respiratory disease. Failure to focus on impaired ASM homeostasis largely explains our failure to find a cure and contributes to the widespread excessive morbidity associated with the condition despite the presence of effective therapies. The mechanisms responsible for destabilizing the normal tight control of ASM and hence airways caliber in post-natal life are unknown but it is clear that atopic inflammation is neither necessary nor sufficient. Loss of homeostasis results in excessive ASM contraction which, in those with poor control, is manifest by variations in airflow resistance over short periods of time. During viral exacerbations, the ability to respond to bronchodilators is partially or almost completely lost, resulting in ASM being "locked down" in a contracted state. Corticosteroids appear to restore normal or near normal homeostasis in those with poor control and restore bronchodilator responsiveness during exacerbations. The mechanism of action of corticosteroids is unknown and the assumption that their action is solely due to "anti-inflammatory" effects needs to be challenged. ASM, in evolutionary terms, dates to the earliest land dwelling creatures that required muscle to empty primitive lungs. ASM appears very early in embryonic development and active peristalsis is essential for the formation of the lungs. However, in post-natal life its only role appears to be to maintain airways in a configuration that minimizes resistance to airflow and dead space. In health, significant constriction is actively prevented, presumably through classic negative feedback loops. Disruption of this robust homeostatic control can develop at any age and results in asthma. In order to develop a cure, we need to move from our current focus on immunology and inflammatory pathways to work that will lead to an understanding of the mechanisms that contribute to ASM stability in health and how this is disrupted to cause asthma. This requires a radical change in the focus of most of "asthma research."

Respiratory Syncytial Virus Infection Promotes Necroptosis and HMGB1 Release by Airway Epithelial Cells.

Rationale: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown.Objectives: To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via HMGB1 (high mobility group box 1) release.Methods: Nasopharyngeal samples were collected from children presenting to the hospital with acute respiratory infection. Primary human AECs and neonatal mice were inoculated with RSV and murine Pneumovirus, respectively. Necroptosis was determined via viability assays and immunohistochemistry for RIPK1 (receptor-interacting protein kinase-1), MLKL (mixed lineage kinase domain-like pseudokinase) protein, and caspase-3. Necroptosis was blocked using pharmacological inhibitors and RIPK1 kinase-dead knockin mice.Measurements and Main Results: HMGB1 levels were elevated in nasopharyngeal samples of children with acute RSV infection. RSV-induced epithelial cell death was associated with increased phosphorylated RIPK1 and phosphorylated MLKL but not active caspase-3 expression. Inhibition of RIPK1 or MLKL attenuated RSV-induced HMGB1 translocation and release, and lowered viral load. MLKL inhibition increased active caspase-3 expression in a caspase-8/9-dependent manner. In susceptible mice, Pneumovirus infection upregulated RIPK1 and MLKL expression in the airway epithelium at 8 to 10 days after infection, coinciding with AEC sloughing, HMGB1 release, and neutrophilic inflammation. Genetic or pharmacological inhibition of RIPK1 or MLKL attenuated these pathologies, lowered viral load, and prevented type 2 inflammation and airway remodeling. Necroptosis inhibition in early life ameliorated asthma progression induced by viral or allergen challenge in later life.Conclusions: Pneumovirus infection induces AEC necroptosis. Inhibition of necroptosis may be a viable strategy to limit the severity of viral bronchiolitis and break its nexus with asthma.

'Dry' and 'wet' cough: how reliable is parental reporting?

Introduction: Chronic cough in childhood is common and causes much parental anxiety. Eliciting a diagnosis can be difficult as it is a non-specific symptom indicating airways inflammation and this may be due to a variety of aetiologies. A key part of assessment is obtaining an accurate cough history. It has previously been shown that parental reporting of 'wheeze' is frequently inaccurate. This study aimed to determine whether parental reporting of the quality of a child's cough is likely to be accurate. Methods: Parents of 48 'new' patients presenting to a respiratory clinic with chronic cough were asked to describe the nature of their child's cough. They were then shown video clips of different types of cough using age-appropriate examples, and their initial report was compared with the types of cough chosen from the video. Results: In a quarter of cases, the parents chose a video clip of a 'dry' or 'wet' cough having given the opposite description. In a further 20% parents chose examples of both 'dry' and 'wet' coughs despite having used only one descriptor. Discussion: While the characteristics of a child's cough carry important information that may be helpful in reaching a diagnosis, clinicians should interpret parental reporting of the nature of a child's cough with some caution in that one person's 'dry' cough may very well be another person's 'wet' cough.

Key paediatric messages from the 2017 European Respiratory Society International Congress.

In this article, the group chairs of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting findings presented at the 2017 ERS International Congress, which was held in Milan, Italy.

PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production.

Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D synthase expression and increased PGD2 release by cultured human primary airway epithelial cells (AECs). Moreover, PGD2 production was elevated in nasopharyngeal samples from young infants hospitalized with RSV bronchiolitis compared to healthy controls. In a neonatal mouse model of severe viral bronchiolitis, DP2 antagonism decreased viral load, immunopathology, and morbidity and ablated the predisposition for subsequent asthma onset in later life. This protective response was abolished upon dual DP1/DP2 antagonism and replicated with a specific DP1 agonist. Rather than mediating an effect via type 2 inflammation, the beneficial effects of DP2 blockade or DP1 agonism were associated with increased interferon-λ (IFN-λ) [interleukin-28A/B (IL-28A/B)] expression and were lost upon IL-28A neutralization. In RSV-infected AEC cultures, DP1 activation up-regulated IFN-λ production, which, in turn, increased IFN-stimulated gene expression, accelerating viral clearance. Our findings suggest that DP2 antagonists or DP1 agonists may be useful antivirals for the treatment of viral bronchiolitis and possibly as primary preventatives for asthma.

Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion.

Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a). In adult mice, pDC depletion predisposed to severe bronchiolitis only after antibiotic treatment. Consistent with a protective role for the microbiome, treatment of pDC-depleted neonates with the microbial-derived metabolite propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases. In children with viral bronchiolitis, nasal propionate levels were decreased and correlated with an IL-6high/IL-10low microenvironment. We highlight a common but age-related Sema4a-mediated pathway by which pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis and subsequent asthma.

Correction to: Effect of inhaled corticosteroid particle size on asthma efficacy and safety outcomes: a systematic literature review and meta-analysis.

CORRECTION: After publication of this work [1] it was noticed that the author name Rachael L. DiSantostefano was not spelt correctly as there was a space in her surname between 'Di' and 'Santostefano'. The publisher apologises for this error.

The impact of persistent bacterial bronchitis on the pulmonary microbiome of children.

INTRODUCTION: Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and 24 children with PBB, with an additional directed sample obtained from PBB patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. RESULTS: No significant difference in bacterial diversity or community composition (R2 = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R2 = 0.08, P = 0.004) was observed among controls, in comparison with patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. CONCLUSION: The bacteria present in the lungs of patients with PBB were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.

ERS statement on protracted bacterial bronchitis in children.

This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.

Persistent and Recurrent Bacterial Bronchitis-A Paradigm Shift in Our Understanding of Chronic Respiratory Disease.

The recent recognition that the conducting airways are not "sterile" and that they have their own dynamic microbiome, together with the rapid advances in our understanding of microbial biofilms and their roles in the causation of respiratory diseases (such as chronic bronchitis, sinusitis, and chronic otitis media), permit us to update the "vicious circle" hypothesis of the causation of bronchiectasis. This proposes that chronic inflammation driven by persistent bacterial bronchitis (PBB) causes damage to both the epithelium, resulting in impaired mucociliary clearance, and to the airway wall, which eventually manifests as bronchiectasis. The link between a "chronic bronchitis" and a persistence of bacterial pathogens, such as non-typable Haemophilus influenzae, was first made more than 100 years ago, and its probable role in the causation of bronchiectasis was proposed soon afterward. The recognition that the "usual suspects" are adept at forming biofilms and hence are able to persist and dominate the normal dynamically changing "healthy microbiome" of the conducting airways provides an explanation for the chronic colonization of the bronchi and for the associated chronic neutrophil-dominated inflammation characteristic of a PBB. Understanding the complex interaction between the host and the microbial communities of the conducting airways in health and disease will be a key component in optimizing pulmonary health in the future.

The Influence of the Microbiome on Early-Life Severe Viral Lower Respiratory Infections and Asthma-Food for Thought?

Severe viral lower respiratory infections are a major cause of infant morbidity. In developing countries, respiratory syncytial virus (RSV)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. Susceptibility to severe RSV-bronchiolitis is governed by gene-environmental interactions that affect the host response to RSV infection. Emerging evidence suggests that the excessive inflammatory response and ensuing immunopathology, typically as a consequence of insufficient immunoregulation, leads to long-term changes in immune cells and structural cells that render the host susceptible to subsequent environmental incursions. Thus, the initial host response to RSV may represent a tipping point in the balance between long-term respiratory health or chronic disease (e.g., asthma). The composition and diversity of the microbiota, which in humans stabilizes in the first year of life, critically affects the development and function of the immune system. Hence, perturbations to the maternal and/or infant microbiota are likely to have a profound impact on the host response to RSV and susceptibility to childhood asthma. Here, we review recent insights describing the effects of the microbiota on immune system homeostasis and respiratory disease and discuss the environmental factors that promote microbial dysbiosis in infancy. Ultimately, this knowledge will be harnessed for the prevention and treatment of severe viral bronchiolitis as a strategy to prevent the onset and development of asthma.

Effect of inhaled corticosteroid particle size on asthma efficacy and safety outcomes: a systematic literature review and meta-analysis.

BACKGROUND: Inhaled corticosteroids (ICS) are the primary treatment for persistent asthma. Currently available ICS have differing particle size due to both formulation and propellant, and it has been postulated that this may impact patient outcomes. This structured literature review and meta-analysis compared the effect of small and standard particle size ICS on lung function, symptoms, rescue use (when available) and safety in patients with asthma as assessed in head-to-head randomized controlled trials (RCTs). METHODS: A systematic literature search of MEDLINE was performed to identify RCTs (1998-2014) evaluating standard size (fluticasone propionate-containing medications) versus small particle size ICS medication in adults and children with asthma. Efficacy outcomes included forced expiratory volume in 1 s (FEV1), morning peak expiratory flow (PEF), symptom scores, % predicted forced expiratory flow between 25 and 75% of forced vital capacity (FEF25-75%), and rescue medication use. Safety outcomes were also evaluated when available. RESULTS: Twenty-three independent trials that met the eligibility criteria were identified. Benefit-risk plots did not demonstrate any clinically meaningful differences across the five efficacy endpoints considered and no appreciable differences were noted for most safety endpoints. Meta-analysis results, using a random-effects model, demonstrated no significant difference between standard and small size particle ICS medications in terms of effects on mean change from baseline FEV1 (L) (-0.011, 95% confidence interval [CI]: -0.037, 0.014 [N = 3524]), morning PEF (L/min) (medium/low doses: -3.874, 95% CI: -10.915, 3.166 [N = 1911]; high/high-medium doses: 5.551, 95% CI: -1.948, 13.049 [N = 749]) and FEF25-75% predicted (-2.418, 95% CI: -6.400; 1.564 [N = 115]). CONCLUSIONS: Based on the available literature, no clinically significant differences in efficacy or safety were observed comparing small and standard particle size ICS medications for the treatment of asthma. TRIAL REGISTRATION: GSK Clinical Study Register No: 202012 .

STAAR: a randomised controlled trial of electronic adherence monitoring with reminder alarms and feedback to improve clinical outcomes for children with asthma.

BACKGROUND: Suboptimal adherence to inhaled steroids is common in children with asthma and is associated with poor disease control, reduced quality of life and even death. Previous studies using feedback of electronically monitored adherence data have demonstrated improved adherence, but have not demonstrated a significant impact on clinical outcomes. The aim of this study was to determine whether introduction of this approach into routine practice would result in improved clinical outcomes. METHODS: Children with asthma aged 6-16 years were randomised to the active intervention consisting of electronic adherence monitoring with daily reminder alarms together with feedback in the clinic regarding their inhaled corticosteroid (ICS) use or to the usual care arm with adherence monitoring alone. All children had poorly controlled asthma at baseline, taking ICS and long-acting ß-agonists. Subjects were seen in routine clinics every 3 months for 1 year. The primary outcome was the Asthma Control Questionnaire (ACQ) score. Secondary outcomes included adherence and markers of asthma morbidity. RESULTS: 77 of 90 children completed the study (39 interventions, 38 controls). Adherence in the intervention group was 70% vs 49% in the control group (p≤0.001). There was no significant difference in the change in ACQ, but children in the intervention group required significantly fewer courses of oral steroids (p=0.008) and fewer hospital admissions (p≤0.001). CONCLUSIONS: The results indicate that electronic adherence monitoring with feedback is likely to be of significant benefit in the routine management of poorly controlled asthmatic subjects. TRIAL REGISTRATION NUMBER: NCT02451709; pre-result.