Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

Assessment of ownership of smart devices and the acceptability of digital health data sharing

Abstract Smart portable devices- smartphones and smartwatches- are rapidly being adopted by the general population, which has brought forward an opportunity to use the large volumes of physiological, behavioral, and activity data continuously being collected by these devices in naturalistic settings to perform research, monitor health, and track disease. While these data can serve to revolutionize health monitoring in research and clinical care, minimal research has been conducted to understand what motivates people to use these devices and their interest and comfort in sharing the data. In this study, we aimed to characterize the ownership and usage of smart devices among patients from an expansive academic health system in the southeastern US and understand their willingness to share data collected by the smart devices. We conducted an electronic survey of participants from an online patient advisory group around smart device ownership, usage, and data sharing. Out of the 3021 members of the online patient advisory group, 1368 (45%) responded to the survey, with 871 female (64%), 826 and 390 White (60%) and Black (29%) participants, respectively, and a slight majority (52%) age 58 and older. Most of the respondents (98%) owned a smartphone and the majority (59%) owned a wearable. In this population, people who identify as female, Hispanic, and Generation Z (age 18–25), and those completing higher education and having full-time employment, were most likely to own a wearable device compared to their demographic counterparts. 50% of smart device owners were willing to share and 32% would consider sharing their smart device data for research purposes. The type of activity data they are willing to share varies by gender, age, education, and employment. Findings from this study can be used to design both equitable and cost-effective digital health studies, leveraging personally-owned smartphones and wearables in representative populations, ultimately enabling the development of equitable digital health technologies

Drug concentration at the site of disease in children with pulmonary tuberculosis.

BackgroundCurrent TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB.ObjectivesTo determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB.MethodsWe quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions.ResultsIsoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions.ConclusionsDespite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid

Drug concentration at the site of disease in children with pulmonary tuberculosis

Background Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. Objectives To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. Methods We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. Results Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. Conclusions Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid

De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder

International audiencePURPOSE:Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292).METHODS:We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. Available data were analyzed to characterize the canonical phenotype and examine genotype-phenotype relationships.RESULTS:Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. All ZNF292 variants were de novo, except in one family with dominant inheritance. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment.CONCLUSION:De novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD

Production of Λ\Lambda and KS0{\rm K}^{0}_{\rm S} in jets in p-Pb collisions at sNN=5\sqrt{s_{\rm NN}} = 5 TeV and pp collisions at s=7\sqrt{s} = 7 TeV

The production of $\Lambda$ baryons and ${\rm K}^{0}_{\rm S}$ mesons (${\rm V}^{0}$ particles) was measured in p-Pb collisions at $\sqrt{s_{\rm NN}} = 5$ TeV and pp collisions at $\sqrt{s} = 7$ TeV with ALICE at the LHC. The production of these strange particles is studied separately for particles associated with hard scatterings and the underlying event to shed light on the baryon-to-meson ratio enhancement observed at intermediate transverse momentum ($p_{\rm T}$) in high multiplicity pp and p-Pb collisions. Hard scatterings are selected on an event-by-event basis with jets reconstructed with the anti-$k_{\rm T}$ algorithm using charged particles. The production of strange particles associated with jets $p_{\rm T,\;jet}^{\rm ch}>10$ GeV/$c$ is reported as a function of $p_{\rm T}$ in both systems; and its dependence on $p_{\rm T}$ with jets $p_{\rm T,\;jet}^{\rm ch}>20$ GeV/$c$ and on angular distance from the jet axis, $R({\rm V}^{0},\;{\rm jet})$, for jets with $p_{\rm T,\;jet}^{\rm ch} > 10$ GeV/$c$ are reported in p-Pb collisions. The results are compared with the strange particle production in the underlying event. The $\Lambda/{\rm K}^{0}_{\rm S}$ ratio associated with jets in p-Pb collisions for $R({\rm V}^{0},\;{\rm jet})<0.4$ is consistent with the ratio measured in pp collisions and with the expectation of jets fragmenting in vacuum given by the PYTHIA event generator

Λc+\Lambda^+_c production in pppp and in pp-Pb collisions at sNN\sqrt {s_{NN}}=5.02 TeV

International audienceThe production cross section of prompt $\mathrm{\Lambda_{c}^{+}}$ charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}} = 5.02$ TeV. The $\mathrm{\Lambda_{c}^{+}}$ and $\rm {\overline{\Lambda}{}_c^-}$ baryons were reconstructed in the hadronic decay channels $\rm \Lambda_{c}^{+} \rightarrow p K^{-}\pi^{+}$ and $\rm \Lambda_{c}^{+}\to p K^{0}_{S}$ and respective charge conjugates. The measured differential cross sections as a function of transverse momentum ($p_{\rm T}$) and the $p_{\rm T}$-integrated $\mathrm{\Lambda_{c}^{+}}$ production cross section in pp and in p-Pb collisions are presented. The $\mathrm{\Lambda_{c}^{+}}$ nuclear modification factor ($R_\mathrm{pPb}$), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the $R_\mathrm{pPb}$ of D mesons. The $\mathrm {\Lambda_{c}^{+}}/\mathrm {D^0}$ ratio is also presented and compared with the light-flavour baryon-to-meson ratios p$/\pi$ and $\Lambda /\mathrm {K^0_S}$, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators

Measurement of Prompt D0^{0}, Λc+\Lambda_{c}^{+}, and Σc0,++\Sigma_{c}^{0,++}(2455) Production in Proton–Proton Collisions at s\sqrt s = 13 TeV

International audienceThe pT-differential production cross sections of prompt D0, Λc+, and Σc0,++(2455) charmed hadrons are measured at midrapidity (|y|&lt;0.5) in pp collisions at s=13  TeV. This is the first measurement of Σc0,++ production in hadronic collisions. Assuming the same production yield for the three Σc0,+,++ isospin states, the baryon-to-meson cross section ratios Σc0,+,++/D0 and Λc+/D0 are calculated in the transverse momentum (pT) intervals 2&lt;pT&lt;12 and 1&lt;pT&lt;24  GeV/c. Values significantly larger than in e+e- collisions are observed, indicating for the first time that baryon enhancement in hadronic collisions also extends to the Σc. The feed-down contribution to Λc+ production from Σc0,+,++ is also reported and is found to be larger than in e+e- collisions. The data are compared with predictions from event generators and other phenomenological models, providing a sensitive test of the different charm-hadronization mechanisms implemented in the models