The difficult coughing child: prolonged acute cough in children

Cough is one of the most common symptoms that patients bring to the attention of primary care clinicians. Cough can be designated as acute (<3 weeks in duration), prolonged acute cough (3 to 8 weeks in duration) or chronic (> 8 weeks in duration). The use of the term ‘prolonged acute cough’ in a cough guideline allows a period of natural resolution to occur before further investigations are warranted. The common causes are in children with post viral or pertussis like illnesses causing the cough. Persistent bacterial bronchitis typically occurs when an initial dry acute cough due to a viral infection becomes a prolonged wet cough remaining long after the febrile illness has resolved. This cough responds to a completed course of appropriate antibiotics

Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model

Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n = 6) and asthmatic (n = 8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p = 0.048, 12.4 (SD 6.1), p = 0.016 and 7.3% (SD 6.6), p = 0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p = 0.02), 32.9% (SD 8.6), p = 0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target

Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p>Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs).</p> <p>Methods</p> <p>To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers.</p> <p>Results</p> <p>RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates.</p> <p>Conclusions</p> <p>The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.</p

Pediatric home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline executive summary

Over the last 30 to 40 years, improvements in technology, as well as changing clinical practice regarding the appropriateness of long-term ventilation in patients with “non-curable” disorders, have resulted in increasing numbers of children surviving what were previously considered fatal conditions. This has come but at the expense of requiring ongoing, long-term prolonged mechanical ventilation (both invasive and noninvasive). Although there are many publications pertaining to specific aspects of home mechanical ventilation (HMV) in children, there are few comprehensive guidelines that bring together all of the current literature. In 2011 the Canadian Thoracic Society HMV Guideline Committee published a review of the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. This current document is intended to be a companion to the 2011 guidelines, concentrating on the issues that are either unique to children on HMV (individuals under 18 years of age), or where common pediatric practice diverges significantly from that employed in adults on long-term home ventilation. As with the adult guidelines,1 this document provides a disease-specific review of illnesses associated with the necessity for long-term ventilation in children, including children with chronic lung disease, spinal muscle atrophy, muscular dystrophies, kyphoscoliosis, obesity hypoventilation syndrome, and central hypoventilation syndromes. It also covers important common themes such as airway clearance, the ethics of initiation of long-term ventilation in individuals unable to give consent, the process of transition to home and to adult centers, and the impact, both financial, as well as social, that this may have on the child\u27s families and caregivers. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information

Effects of IL-13 on normal and asthmatic pediatric bronchial and nasal epithelial cells : IL-13 as a therapeutic target in childhood asthma

Goblet cell hyperplasia (GCH) and decreased ciliogenesis are characteristic features which may be influenced by Th2 cytokines (eg IL-9 and IL-13). Studies have suggested nasal epithelium can be used as a surrogate for bronchial epithelial. AIM In vitro basal mucociliary differentiation and differences in paediatric epithelial cells (normal & asthmatics) exposed to IL-9 and IL-13 were studied. To study the feasibility of nasal epithelium as a replacement for bronchus. METHOD Bronchial (PBECs) and paired nasal brushings (PNECs) obtained from children were differentiated at air liquid interface for 28 days. Cells treated with IL-13, IL-9 or a combination of IL-9/-13. Transeplthelial resistance (TEER), number of ciliated and goblet cells, MUC5AC mRNA expression and relative absorbance of MUC5AC were assessed as a measure of tissue differentiation. RESULTS Asthmatic PBECs (PBEC(A)) had a significant GCH and fewer ciliated cells compared to normal PBEC, (PBEC(N) under un-stimulated conditions. Stimulation with 20ng/ml IL-13 in PBEC(N) and PBEC(A) resulted in GCH and decreased ciliated cell number compared to un-stimulated respective cultures. Similar was also observed in the increase of MUC5AC mRNA expression with 20ng/ml IL-13 in PBEC(A) and PBEC(N). IL-9 alone did not alter goblet cell numbers, however PBEC(N) with the IL-9/IL-13 increased goblet cell number compared with un-stimulated. IL-9 and IL-9/IL-13 stimulated PBEC(N) had reduced ciliated cell numbers compared with un-stimulated. In PBEC(A), only 20ng/ml IL-13 significantly reduced ciliated cell number compared with un-stimulated. Morphological differences observed between asthmatic and normal PNECs and PBECs was also supported by varied cytokine release and functional differences following IL-13 stimulation. CONCLUSION Morphological differences exist between normal and asthmatic PBECs and PNECs under un-stimulated conditions. IL-13 drives PBEC(N) towards an asthmatic phenotype and worsens the phenotype in PBEC(A) with reduced ciliated cell numbers and increased GCH. IL-9 alone did not stimulate GCH in PBEC(N), and showed no synergistic effect with IL-13 in driving GCH. IL-9 and IL-9/13 lowered the number of ciliated cells in PBEC(N), however this was not seen in asthmatic cells. Functional differences exist between PBEC and PNEC therefore questions the suitability of nasal epithelium as a surrogate.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Review: Quality of Life in Children with Non-cystic Fibrosis Bronchiectasis

Non-cystic fibrosis bronchiectasis (NCFB) has gained renewed interest, due to its increasing health-care burden. Annual mortality statistics in England and Wales showed that under 1,000 people die from bronchiectasis each year, and this number is increasing by 3% yearly. Unfortunately, there is a severe lack of well-powered, randomized controlled trials to guide clinicians how to manage NCFB effectively. Quality-of-life (QOL) measures in NCFB are an important aspect of clinical care that has not been studied well. Commonly used disease-specific questionnaires in children with NCFB are the St George’s Respiratory Questionnaire, Short Form-36, the Leicester Cough Questionnaire, and the Parent Cough-Specific Quality of Life questionnaire (PC-QOL). Of these, only the PC-QOL can be used in young children, as it is a parent-proxy questionnaire. We reviewed pediatric studies looking at QOL in children with NCFB and cystic fibrosis. All types of airway clearance techniques appear to be safe and have no significant benefit over each other. Number of exacerbations and hospitalizations correlated with QOL scores, while symptom subscales correlated with lung function, worse QOL, frequent antibiotic requirements, and duration of regular follow-up in only one study. There was a correlation between QOL and age of diagnosis in children with primary ciliary dyskinesia. Other studies have shown no relationship between QOL scores and etiology of NCFB as well as CT changes. As for treatments, oral azithromycin and yoga have demonstrated some improvement in QOL scores. In conclusion, more studies are required to accurately determine important factors contributing to QOL