Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast: a randomised controlled trial investigating the effects on airway inflammation in asthma

<p>Abstract</p> <p>Background</p> <p>Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP) (Seretide™; SFC) and FP plus montelukast (FP/M) on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics.</p> <p>Methods</p> <p>Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function.</p> <p>Results</p> <p>Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94).</p> <p>Conclusion</p> <p>Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC.</p> <p>Study number</p> <p>SAM40030 (SOLTA)</p

Prediction of binding hot spot residues by using structural and evolutionary parameters

In this work, we present a method for predicting hot spot residues by using a set of structural and evolutionary parameters. Unlike previous studies, we use a set of parameters which do not depend on the structure of the protein in complex, so that the predictor can also be used when the interface region is unknown. Despite the fact that no information concerning proteins in complex is used for prediction, the application of the method to a compiled dataset described in the literature achieved a performance of 60.4%, as measured by F-Measure, corresponding to a recall of 78.1% and a precision of 49.5%. This result is higher than those reported by previous studies using the same data set

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research

Subdiagnóstico de DPOC na atenção primária em Aparecida de Goiânia, Goiás Underdiagnosis of COPD at primary health care clinics in the city of Aparecida de Goiânia, Brazil

OBJETIVO: Estimar a prevalência de DPOC não diagnosticada entre indivíduos com fatores de risco para a doença atendidos em unidades de estratégia de saúde da família (UESF) na cidade de Aparecida de Goiânia (GO). MÉTODOS: Os critérios de inclusão foram ter idade > 40 anos, ter história de tabagismo > 20 maços-ano ou de exposição à queima de biomassa > 80 horas-ano e procurar atendimento médico em uma das UESF selecionadas. Todos os indivíduos incluídos no estudo foram submetidos a espirometria para a definição diagnóstica de DPOC. RESULTADOS: Foram avaliados com sucesso 200 indivíduos, a maioria do sexo masculino. A média de idade foi de 65,9 ± 10,5 anos. Tiveram confirmação diagnóstica de DPOC 63 indivíduos. Desses, apenas 18 haviam sido previamente diagnosticados com DPOC (taxa de subdiagnóstico de 71,4%). Não houve diferenças significantes entre os subgrupos com e sem diagnóstico prévio de DPOC em relação a fatores demográficos e fatores de risco. Entretanto, houve diferenças significantes entre esses subgrupos em relação à presença de expectoração, chiado e dispneia (p = 0,047, p = 0,005 e p = 0,047, respectivamente). Os valores de VEF1 e VEF1/CVF, em percentual do previsto, foram significativamente menores nos indivíduos com diagnóstico prévio de DPOC. A DPOC foi predominantemente leve a moderada em ambos os subgrupos. CONCLUSÕES: A taxa de subdiagnóstico da DPOC foi alta nas UBS estudadas. Um terço dos pacientes com fatores de risco para DPOC apresentou critérios clínicos e funcionais para a doença. A espirometria foi subutilizada.<br>OBJECTIVE: To estimate the prevalence of undiagnosed COPD among individuals with risk factors for the disease treated at primary health care clinics (PHCCs) in the city of Aparecida de Goiânia, Brazil. METHODS: Inclusion criteria were being > 40 years of age, having a > 20 pack-year history of smoking or a > 80 hour-year history of exposure to biomass smoke, and seeking medical attention at one of the selected PHCCs. All subjects included in the study underwent spirometry for the diagnosis of COPD. RESULTS: We successfully evaluated 200 individuals, mostly males. The mean age was 65.9 ± 10.5 years. The diagnosis of COPD was confirmed in 63 individuals, only 18 of whom had been previously diagnosed with COPD (underdiagnosis rate, 71.4%). There were no significant differences between the subgroups with and without a previous diagnosis of COPD in relation to demographics and risk factors. However, there were significant differences between these subgroups for the presence of expectoration, wheezing, and dyspnea (p = 0.047; p = 0.005; and p = 0.047, respectively). The FEV1 and FEV1/FVC ratio, expressed as percentages of the predicted values, were significantly lower in the subjects with a previous diagnosis of COPD, which was predominantly mild or moderate in both subgroups. CONCLUSIONS: The rate of underdiagnosis of COPD was high at the PHCCs studied. One third of the patients with risk factors for COPD met the clinical and functional criteria for the disease. It seems that spirometry is underutilized at such facilities