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Introduction: Adverse nutritional factors in early life, such as food insecurity, may affect the risk of developing asthma in childhood, and worsen asthma control. Aim: To systematically review literature on the impact of family food insecurity on prevalence of childhood asthma, and asthma control. Methods: We included cohort, case-control, and cross-sectional studies evaluating food insecurity and the risk of children developing asthma in childhood or having poor asthma control. We used the SCOPUS platform to search several databases, using a predefined strategy. We used the CASP tool to evaluate study quality. We extracted effect sizes for risk of developing asthma or having poor asthma control. Results: From 109 abstracts we included 8 studies. The studies were of adequate quality but methodological heterogeneity precluded meta-analysis. Six studies evaluated the impact of food insecurity on the risk of developing childhood asthma. Of these, five large studies (n 54,207) found that family food insecurity significantly increased risk of children developing asthma (Odds ratio 1.04 – 2.08). One study (n 486) found no increased risk. Two studies evaluated the impact of food insecurity on asthma control. In one (n 553) food insecurity doubled the risk of poor asthma control (OR 2.01) but in the other (n 127) there was no increased risk. Conclusions: Food insecurity may increase the risk of childhood asthma but the impact on asthma control is uncertain. Large epidemiological studies with standardised methodology are required to evaluate the impact of food insecurity on childhood asthma outcomes.

In our specialist clinic we emphasise the importance of healthy living but evidence around prevalence of obesity & fitness in this group is sparse Aim: To explore the prevalence of obesity & poor fitness levels in our asthma clinic & identify risk factors for poor fitness Method: Database analysis of routinely collected data for children who attended clinic since July 2018. BMI percentiles were calculated according to the National Child Measurement Programme, UK (93rd-97th percentile=overweight, 98th-99th percentile=very overweight). Fitness levels were assessed using the Chester step test, giving a valid approximation of VO2 max score. Poor fitness and overweight/very overweight were compared (chi-square or Person’s correlation) against demographic details, socioeconomic status (Postcode index of multiple deprivation index), and markers of asthma control, airway obstruction, and airway inflammation. Results: 99 children (median 12 years IQR 10-15;64% male),of whom 79 (80%) completed a fitness test. 44/99 (44%) were overweight/very overweight (15/99 (15%) and 29/99 (29%) respectively). 31/79 (39%) had sub-average or very low fitness levels. This was associated with female sex (p 0.047), older age (p 0.017) & baseline BMI category (p 0.03). Poor fitness was not associated with clinical or physiological markers of asthma severity, or socioeconomic status. Conclusion: Obesity & poor fitness are highly prevalent in children with asthma. Those at risk include girls, older teenagers & overweight children. Proactive screening to identify poor fitness should be conducted in clinics managing children with severe asthma.The impact of improved fitness on asthma control should also be explored.

Introduction: It is difficult to accurately identify aetiological factors causing breathlessness (symptoms disproportionate to those expected from a given diagnosis that impacts on the ability to exercise). Effective management relies on an accurate diagnosis. Aims: To review routinely collected diagnostic and clinical data of children referred to the complex breathlessness clinic. Methods: Routinely collected data was analysed from May 2017-Jan 2019 from one of the only paediatric complex breathlessness clinics in Europe. Children (including high level athletes) were referred across North West England. The structured diagnostic process included clinical assessment (respiratory, physiotherapy, ENT), physiological measurement, and laryngoscopy pre and post exercise. Tailored follow-up therapy was directed by a specialist physiotherapist. Results: 32 children attended clinic (age 7-18 [mean 14] years; 25/32 [78%] female). 12/32 (38%) were high level athletes; 4/32 (12.5%) were ex-athletes. Aetiological diagnoses identified were: Dysfunctional breathing 17/32 (53%), Deconditioning 12/32 (39%), Anxiety or other psychosocial factors 12/32 (38%), Laryngeal obstruction 9/32 (29%), Asthma 7/32 (22%), Exercise-induced bronchoconstriction 2/32 (6%) and Reaching maximal exercise capacity 2/32 (6%). Following specialist therapies, 23/32(72%) children were discharged due to resolution of symptoms, 6/32 (19%) are currently receiving treatment and 3/32 (9%) did not attend follow-up therapy. Conclusion: Complex breathlessness is caused by multiple factors, and requires a multispecialty diagnostic approach. Tailored therapies had a positive impact on children with complex breathlessness.

Objective This double-blind, randomised, placebo-controlled, two-part study assessed the impact of GSK2981710, a medium-chain triglyceride (MCT) that liberates ketone bodies, on cognitive function, safety, and tolerability in healthy older adults. Methods Part 1 was a four-period dose-selection study (n = 8 complete). Part 2 was a two-period crossover study (n = 80 complete) assessing the acute (Day 1) and prolonged (Day 15) effects of GSK2981710 on cognition and memory-related neuronal activity. Safety and tolerability of MCT supplementation were monitored in both parts of the study. Results The most common adverse event was diarrhoea (100% and 75% of participants in Parts 1 and 2, respectively). Most adverse events were mild to moderate, and 11% participants were withdrawn due to one or more adverse events. Although GSK2981710 (30 g/day) resulted in increased peak plasma β-hydroxybutyrate (BHB) concentrations, no significant improvements in cognitive function or memory-related neuronal activity were observed. Conclusion Over a duration of 14 days, increasing plasma BHB levels with daily administration of GSK2981710 had no effects on neuronal activity or cognitive function. This result indicates that modulating plasma ketone levels with GSK2981710 may be ineffective in improving cognitive function in healthy older adults, or the lack of observed effect could be related to several factors including study population, plasma BHB concentrations, MCT composition, or treatment duration.

Alan S Bell,1,2 Philip J Lawrence,1 Dave Singh,1–3 Alexander Horsley2–4 1The Medicines Evaluation Unit, Wythenshawe Hospital, Manchester, UK; 2Division of Infection Immunity and Respiratory Medicine, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK; 3Manchester Academic Health Science Centre, Manchester, UK; 4Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK Background: Lung clearance index (LCI), derived from multiple-breath washout (MBW), is a well-established assessment of ventilation inhomogeneity in cystic fibrosis but has not been widely applied in other conditions characterized by heterogeneous airways disease, such as COPD. The aim of this study was to evaluate the sensitivity, repeatability, and practicality of LCI in patients with COPD. Methods: Fifty-four COPD patients completed MBW using nitrogen as the washout tracer gas (MBWN2, measured using an Exhalyzer™ device), spirometry, and plethysmography. Twenty patients repeated MBWN2, MBWSF6 (using a separate Innocor™ gas analyzer to measure washout of the exogenous trace sulphur hexafluoride), and spirometry at a second visit ≥24 hours later. Results: Mean (SD) COPD LCI measured by nitrogen washout (LCIN2) was 12.1 (2.2); mean (SD) LCI Z-score 5.8 (2.0). LCIN2 increased across Global Initiative for Obstructive Lung Disease stages 1 to 3 and was abnormal (Z-score >1.65) in all COPD patients, including those with forced expiratory volume in 1 second (FEV1) ≥80% predicted. LCI was repeatable (median intra-test coefficient of variation 4.1%) and reproducible (limits of agreement -1.8 to 1.6) after mean of 16 days. Functional residual capacity (FRC) measurements were significantly greater using nitrogen than SF6 or plethysmography: mean FRC measured by nitrogen washout (FRCN2) 139% predicted versus FRC measured by plethysmography 125% predicted, p

Most antibiotics are prescribed in primary care, and commonly for respiratory tract infections (RTIs). Narrow-spectrum phenoxymethylpenicillin is the antibiotic of choice for RTIs in the Scandinavian countries, while broader spectrum amoxicillin is used in most other European countries. This review summarizes the knowledge of the effect of phenoxymethylpenicillin versus amoxicillin for infections treated in ambulatory care. We searched PubMed/Medline and Embase for trials comparing the clinical effect of phenoxymethylpenicillin and amoxicillin. The Norwegian Knowledge Centre for the Health Services’ checklist was used to assess risk of bias. In total, 1687 studies were identified, and 18 of these fulfilled the inclusion criteria. One additional study was found as a reference. The randomized controlled trials revealed no significant differences in clinical effect in acute sinusitis (three RCTs), GAS tonsillitis (11 RCTs) and Lyme borreliosis (two RCTs). One RCT on community-acquired pneumonia found amoxicillin to be superior, while the results were conflicting in the two RCTs on acute otitis. The results suggest that non-Scandinavian countries should consider phenoxymethylpenicillin as the treatment of choice for RTIs because of its narrower spectrum. More studies should be conducted on the clinical effect of phenoxymethylpenicillin versus amoxicillin for acute otitis and lower RTIs.

Background The characteristics and natural history of GOLD B COPD patients are not well described. The clinical characteristics and natural history of GOLD B patients over 1 year in a multicentre cohort of COPD patients in the COPDMAP study were assessed. We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression. Methods Three hundred seventy COPD patients were assessed at baseline and 12 months thereafter. Demographics, lung function, health status, 6 min walk tests and levels of systemic inflammation were assessed. Students t tests and Mann Whitney-U tests were used. Results One hundred seven (28.9%) of patients were categorised as GOLD B at baseline. These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted). More GOLD B patients were current smokers (p = 0.031), had chronic bronchitis (p = 0.0003) and cardiovascular comorbidities (p = 0.019) compared to GOLD A. At 12 months, 25.3% of GOLD B patients progressed to GOLD D. These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p = 0.019 and CAT, 21.0 v 14.0, p = 0.006) and lower FEV1 (60% v 69% p = 0.014) at baseline compared to stable patients who remained in GOLD B. Conclusions Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline. A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0384-8) contains supplementary material, which is available to authorized users.

Rationale The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors, from feeding, motivation and arousal, to sleep and wakefulness. Orexin signaling is thus an exciting potential therapeutic target for disorders of sleep, feeding, addiction, and stress. Objectives/methods Here, we investigated the low dose pharmacology of orexin receptor antagonist, SB-649868, on neuroendocrine, sympathetic nervous system, and behavioral responses to insulin-induced hypoglycemic stress, in 24 healthy male subjects (aged 18–45 years; BMI 19.0–25.9 kg/m2), using a randomized, double-blind, placebo-controlled, within-subject crossover design. Alprazolam, a licensed benzodiazepine anxiolytic, was used as a positive comparator, as it has previously been validated using the insulin tolerance test (ITT) model in humans. Results Of the primary endpoints, ITT induced defined increases in pulse rate, plasma cortisol, and adrenocorticotropic hormone in the placebo condition, but these responses were not significantly impacted by alprazolam or SB-649868 pre-treatment. Of the secondary endpoints, ITT induced a defined increase in plasma concentrations of adrenaline, noradrenaline, growth hormone (GH), and prolactin in the placebo condition. Alprazolam pre-treatment significantly reduced the GH response to ITT (p

Background The characteristics and natural history of GOLD B patients are not well described. Aims Objectives To assess the clinical characteristics and natural history of GOLD B patients over one year in a multicentre cohort of COPD patients in the COPDMAP study. We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression. Methods 370 COPD patients were assessed at baseline and 12 months thereafter. Demographics, lung function, health status, 6 minute walk test and levels of systemic inflammation were assessed. Students t tests and Mann Whitney-U test were used as appropriate. Results 107 (28.9%) of patients were categorised as GOLD B at baseline. These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted). More GOLD B patients were current smokers ( p =0.031), had chronic bronchitis ( p =0.0003) and cardiovascular comorbidities ( p =0.019) compared to GOLD A. At 12 months, 25.3% of GOLD B patients progressed to GOLD D. These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p =0.019 and CAT, 21.0 v 14.0, p =0.006) and lower FEV 1 (60% v 69% p =0.014) at baseline compared to stable patients who remained in GOLD B. Conclusions Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline. A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients.

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference ± 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = −17.9 mA (−27.9, −7.9) P < 0.001; ACW-PT: V1-V3 = −3.38°C (−5.33, −1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [−35.9 (−60, −11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Aδ fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 ( r = −0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

BACKGROUND: This study aimed to evaluate the use of dried blood spots (DBSs) and dried plasma spots (DPSs) locally collected in 2 rural dispensaries in Cameroon for the quantification of HIV-1 RNA. METHODS: Forty-one subjects were sampled and spots of whole blood and plasma were deposited onto Whatman 903 cards and dried at ambient temperature under local conditions. Two sets of DBS and DPS cards were done per patient. The rest of the liquid plasma (LP) was frozen until use. LPs were tested at the "Chantal Biya" International Reference Centre (Yaounde Cameroon) by the Abbott Real-Time HIV-1 assay (Abbott Molecular Diagnostics Wiesbaden Germany). One series of DBS and DPS was transported and tested between 2 and 6 weeks later at the Virology Laboratory of Saint-Etienne (France). The second series was routed by mail and tested after up to 3 months of storage at ambient temperature. RESULTS: From the first series the correlation rate between viral loads obtained from LP and DBS and from LP and DPS was 0.98 and 0.99 respectively; specificity of DBS and DPS results was 100%. The results obtained from the second series indicate a great stability of DBS after long-term storage. CONCLUSION: This study demonstrates that DBSs collected under local conditions in resource-limited settings are suitable for the differed quantification of HIV-1 RNA.

Mozambique's food crisis is one of the most disastrous in Africa. Undeniably a result of systematic South African destabilisation, and made worse in the last years by drought, it has its origins in the colonial structure of agriculture and the shock of the sudden Portuguese exodus at Independence. But the paper explores, as Frelimo's 1983 Fourth Congress did, whether policy choices have not made matters worse. Attention is drawn to the last few years’ emphasis on the former settler sector, its conversion to complex, costly and not very productive state farms; to low prices of food, to sustain an essentially Portuguese urban diet — all to the detriment of peasant farming.

The protection that a powered air-purifying respirator afforded to ladle and furnace attendants who were exposed to lead, copper and zinc fumes in a brass foundry was found by measuring metal levels at the lapel and at nose level inside the respirator. Respirator fit was evaluated by use of a hot-wire anemometer at the face/Tyvek seal interfaces, and at the exit of the respirator. Effective protection factors for lead ranged from 1.05 to 67. Ergonomic factors and engineering controls are also discussed.