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.
Adherence to inhaled steroids is suboptimal in many children with asthma and can lead to poor disease control. Many previous studies in paediatric populations have used subjective and inaccurate ...adherence measurements, reducing their validity. Adherence studies now often use objective electronic monitoring, which can give us an accurate indication of the extent of non-adherence in children with asthma. A review of the studies using electronic adherence monitoring shows that half of them report mean adherence rates of 50% or below, and the majority report rates below 75%. Reasons for non-adherence are both intentional and non-intentional, incorporating illness perceptions, medication beliefs and practical adherence barriers. Interventions to improve adherence in the paediatric population have had limited success, with the most effective containing both educational and behavioural aspects.
: 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.
: To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via HMGB1 (high mobility group box 1) release.
: 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
, 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.
: 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,
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.
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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.
The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic ...databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most.
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.
Pulmonary infections remain a major cause of infant and child mortality worldwide and are responsible for a substantial burden of morbidity. During the 2015 European Respiratory Society International ...Congress in Amsterdam, some of the main findings from peer-reviewed articles addressing this topic that were published in the preceding 12 months were reviewed in a Paediatric Clinical Year in Review session. The following article highlights some of the insights provided by these articles into the complex interactions of the human host with the extensive and dynamic populations of microorganisms that call an individual "home".
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Dysfunctional breathing (DB) is common, frequently unrecognised and responsible for a substantial burden of morbidity. Previously lack of clarity in the use of the term and the use of ...multiple terms to describe the same condition has hampered our understanding. DB can be defined as an alteration in the normal biomechanical patterns of breathing that result in intermittent or chronic symptoms. It can be subdivided into thoracic and extra thoracic forms. Thoracic DB is characterised by breathing patterns involving relatively inefficient, excessive upper chest wall activity with or without accessory muscle activity. This is frequently associated with increased residual volume, frequent sighing and an irregular pattern of respiratory effort. It may be accompanied by true hyperventilation in the minority of subjects. Extra thoracic forms include paradoxical vocal cord dysfunction and the increasingly recognised supra-glottic ‘laryngomalacia’ commonly seen in young sportsmen and women. While the two forms would appear to be two discreet entities they often share common factors in aetiology and respond to similar interventions. Hence both forms are considered in this review which aims to generate a more coherent approach to understanding, diagnosing and treating these conditions.
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