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

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

Cesarean or vaginal birth does not impact the longitudinal development of the gut microbiome in a cohort of exclusively preterm infants

The short and long-term impact of birth mode on the developing gut microbiome in neonates has potential implications for the health of infants. In term infants, the microbiome immediately following birth across multiple body sites corresponds to birth mode, with increased Bacteroides in vaginally delivered infants. We aimed to determine the impact of birth mode of the preterm gut microbiome over the first 100 days of life and following neonatal intensive care unit (NICU) discharge. In total, 867 stool samples from 46 preterm infants (21 cesarean and 25 vaginal), median gestational age 27 weeks, were sequenced (V4 region 16S rRNA gene, Illumina MiSeq). Of these, 776 samples passed quality filtering and were included in the analysis. The overall longitudinal alpha-diversity and within infant beta-diversity was comparable between cesarean and vaginally delivered infants. Vaginally delivered infants kept significantly more OTUs from 2 months of life and following NICU discharge, but OTUs lost, gained, and regained were not different based on birth mode. Furthermore, the temporal progression of dominant genera was comparable between birth modes and no significant difference was found for any genera following adjustment for covariates. Lastly, preterm gut community types (PGCTs) showed some moderate differences in very early life, but progressed toward a comparable pattern by week 5. No PGCT was significantly associated with cesarean or vaginal birth. Unlike term infants, birth mode was not significantly associated with changes in microbial diversity, composition, specific taxa, or overall microbial development in preterm infants. This may result from the dominating effects of NICU exposures including the universal use of antibiotics immediately following birth and/or the lack of Bacteroides colonizing preterm infants

Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford record linkage study

Background: There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children. Methods: Analysis of data from the Oxford record linkage study (ORLS) to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999. Results: Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s), low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR) 3.1, 95% confidence interval 2.7-3.6), male sex (versus female, 1.8, 1.7-2.0), low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3), maternal smoking (1.1, 1.0-1.3) and delivery by caesarean section (1.2; 1.0-1.3). In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7) and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2). Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7), age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7); high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82). Hospital admission for asthma in people aged over six was more common in males than females (1.4; 1.2-1.5); but, by the teenage years, the sex ratio reversed and admission was more common in females than males. Conclusion: Several maternal characteristics and perinatal factors are associated with an elevated risk of hospital admission for asthma in the child in later life. </p

Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro

BACKGROUND AND PURPOSEMucociliary malfunction occurs in chronic obstructive pulmonary disease (COPD) and compromised functions of ciliated bronchial epithelial cells may contribute to this. Cigarette smoke, a major risk factor for COPD, impairs ciliary beat frequency (CBF). cAMP augments CBF. This in vitro study addressed, in differentiated, primary human bronchial epithelial cells, whether roflumilast N-oxide, a PDE4 inhibitor, (i) augments CBF; (ii) prevents the reduction in CBF induced by cigarette smoke extract (CSE); and (iii) protects against the loss of the ciliated phenotype following long-term CSE exposure.EXPERIMENTAL APPROACHAir-liquid interface cultured human bronchial epithelial cells were incubated with roflumilast N-oxide and exposed to CSE. CBF was assessed by digital high speed video microscopy (DHSV). Ciliated cells were characterized by β-tubulin IV staining and analyses of Foxj1 and Dnai2 mRNA and protein (real-time quantitative PCR, Western blotting).KEY RESULTSRoflumilast N-oxide concentration-dependently triggered a rapid and persistent increase in CBF and reversed the decrease in CBF following CSE. Long-term incubation of bronchial epithelial cells with CSE resulted in a loss in ciliated cells associated with reduced expression of the ciliated cell markers Foxj1 and Dnai2. The PDE4 inhibitor prevented this loss in the ciliated cell phenotype and the compromised Foxj1 and Dnai2 expression. The enhanced release of IL-13 following CSE, a cytokine that diminishes the proportion of ciliated cells and in parallel, reduces Foxj1 and Dnai2, was reversed by roflumilast N-oxide.CONCLUSION AND IMPLICATIONSRoflumilast N-oxide protected differentiated human bronchial epithelial cells from reduced CBF and loss of ciliated cells following CSE

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.Peer reviewedPublisher PD

Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay

<p>Abstract</p> <p>Background</p> <p>Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV.</p> <p>Methods</p> <p>Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010).</p> <p>Results</p> <p>Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed.</p> <p>Conclusions</p> <p>DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the "PCR era", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.</p