The bronchodilator response in preschool children: A systematic review

BACKGROUND: The bronchodilator response (BDR) is frequently used to support diagnostic and therapeutic decision-making for children who wheeze. However, there is little evidence-based guidance describing the role of BDR testing in preschool children and it is unclear whether published cut-off values, which are derived from adult data, can be applied to this population. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases (inception-September 2015) for studies reporting response to a bronchodilator in healthy preschool children, response following placebo inhalation, and the diagnostic efficacy of BDR compared with a clinical diagnosis of asthma/recurrent wheezing. FINDINGS: We included 14 studies. Thirteen studies provided BDR data from healthy preschool children. Two studies reported response to placebo in preschool children with asthma/recurrent wheezing. Twelve studies compared BDR measurements from preschool children with asthma/recurrent wheeze to those from healthy children and seven of these studies reported diagnostic efficacy. Significant differences between the BDR measured in healthy preschool children compared with that in children with asthma/recurrent wheeze were demonstrated in some, but not all studies. Techniques such as interrupter resistance, oscillometry, and plethysmography were more consistently successfully completed than spirometry. Between study heterogeneity precluded determination of an optimum technique. INTERPRETATION: There is little evidence to suggest spirometry-based BDR can be used in the clinical assessment of preschool children who wheeze. Further evaluation of simple alternative techniques is required. Future studies should recruit children in whom airways disease is suspected and should evaluate the ability of BDR testing to predict treatment response

paediatric respiratory disease past present and future

Paediatric respiratory disease has changed in the past 20 yrs; we could fill a whole issue of the journal paying tribute to our famous forebears. We are posing new challenges to our colleagues in the field of adult respiratory disease. They have to learn to deal with conditions that 20 yrs ago were rare in the adult chest clinic, such as cystic fibrosis (CF) and the long-term consequences of premature birth and congenital malformations of the respiratory tract. Furthermore, studies in childhood are challenging pathophysiological concepts throughout life. The many great prospective birth cohort studies have shed light on the different patterns of wheezing, their risk factors and their evolution through childhood. Who would have thought it was good to be born in a barn! It is becoming increasingly clear that even for "adult" diseases, such as chronic obstructive pulmonary disease (COPD), antenatal and early life events are at least as important as smoking in adulthood 1. CF has become a disease also of adults 2. Although many factors have contributed, the main reason has been the development of expert special CF centres, a model increasingly adopted by adult teams. This can serve as a model for other diseases; how a well-structured multidisciplinary approach to treatment can translate into benefits for patients. Perhaps numerically the most important achievement is in the field of public health. The benefit of the decrease in invasive bacterial infections, due to vaccination programmes for infants, is among the most important achievements of the past. Other areas of change include the survival of ever smaller preterm neonates. These children are reaching adult life with impaired lung function and abnormal computed tomography scans. What will happen to their ageing lungs? Interstitial lung disease (ILD) is becoming increasingly well understood, with new genetic entities, such as

Energetic Components of Cooperative Protein Folding

A new lattice protein model with a four-helix bundle ground state is analyzed by a parameter-space Monte Carlo histogram technique to evaluate the effects of an extensive variety of model potentials on folding thermodynamics. Cooperative helical formation and contact energies based on a 5-letter alphabet are found to be insufficient to satisfy calorimetric and other experimental criteria for two-state folding. Such proteinlike behaviors are predicted, however, by models with polypeptide-like local conformational restrictions and environment-dependent hydrogen bonding-like interactions.Comment: 11 pages, 4 postscripts figures, Phys. Rev. Lett. (in press

Role of Secondary Motifs in Fast Folding Polymers: A Dynamical Variational Principle

A fascinating and open question challenging biochemistry, physics and even geometry is the presence of highly regular motifs such as alpha-helices in the folded state of biopolymers and proteins. Stimulating explanations ranging from chemical propensity to simple geometrical reasoning have been invoked to rationalize the existence of such secondary structures. We formulate a dynamical variational principle for selection in conformation space based on the requirement that the backbone of the native state of biologically viable polymers be rapidly accessible from the denatured state. The variational principle is shown to result in the emergence of helical order in compact structures.Comment: 4 pages, RevTex, 4 eps figure

Very Low-Mass Objects in the Coronet Cluster: The Realm of the Transition Disks

We present optical and IR spectra of a set of low-mass stars and brown dwarfs in the Coronet cluster (aged ~1Myr), obtained with the multifiber spectrograph FLAMES/VLT and IRS/Spitzer. The optical spectra reveal spectral types between M1 and M7.5, confirm the youth of the objects (via Li 6708 A absorption), and show the presence of accretion (via Halpha) and shocks (via forbidden line emission). The IRS spectra, together with IR photometry from the IRAC/MIPS instruments on Spitzer and 2MASS, confirm the presence of IR excesses characteristic of disks around ~70% of the objects. Half of the disks do not exhibit any silicate emission, or present flat features characteristic of large grains. The rest of the disks show silicate emission typical of amorphous and crystalline silicate grains a few microns in size. About 50% of the objects with disks do not show near-IR excess emission, having "transitional" disks, according to their classical definition. This is a very high fraction for such a young cluster. The large number of "transitional" disks suggests lifetimes comparable to the lifetimes of typical optically thick disks. Therefore, these disks may not be in a short-lived phase, intermediate between Class II and Class III objects. The median spectral energy distribution of the disks in the Coronet cluster is also closer to a flat disk than observed for the disks around solar-type stars in regions with similar age. The differences in the disk morphology and evolution in the Coronet cluster could be related to fact that these objects have very late spectral types compared to the solar-type stars in other cluster studies. Finally, the optical spectroscopy reveals that one of the X-ray sources is produced by a Herbig Haro object in the cloud.Comment: 51 pages, 13 figures, 10 table

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. Methods: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. Results: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. Conclusion: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.</p

Herbig Ae/Be Stars in nearby OB associations

We have carried out a study of the early type stars in nearby OB associations spanning an age range of $\sim$ 3 to 16 Myr, with the aim of determining the fraction of stars which belong to the Herbig Ae/Be class. We studied the B, A, and F stars in the nearby ($\le 500$ pc) OB associations Upper Scorpius, Perseus OB2, Lacerta OB1, and Orion OB1, with membership determined from Hipparcos data. We obtained spectra for 440 Hipparcos stars in these associations, from which we determined accurate spectral types, visual extinctions, effective temperatures, luminosities and masses, using Hipparcos photometry. Using colors corrected for reddening, we find that the Herbig Ae/Be stars and the Classical Be stars (CBe) occupy clearly different regions in the JHK diagram. Thus, we use the location on the JHK diagram, as well as the presence of emission lines and of strong 12 microns flux relative to the visual to identify the Herbig Ae/Be stars in the associations. We find that the Herbig Ae/Be stars constitute a small fraction of the early type stellar population even in the younger associations. Comparing the data from associations with different ages and assuming that the near-infrared excess in the Herbig Ae/Be stars arises from optically thick dusty inner disks, we determined the evolution of the inner disk frequency with age. We find that the inner disk frequency in the age range 3 - 10 Myr in intermediate mass stars is lower than that in the low mass stars (< 1msun). This indicates that the time-scales for disk evolution are much shorter in the intermediate mass stars, which could be a consequence of more efficient mechanisms of inner disk dispersal (viscous evolution, dust growth and settling toward the midplane).Comment: 34 pages, 10 figure