Socioeconomic deprivation is known to be associated with worse outcomes in asthma, but there is a lack of population-based evidence of its impact across all stages of patient care. We investigated ...the association of socioeconomic deprivation with asthma-related care and outcomes across primary and secondary care and with asthma-related death in Wales.
We constructed a national cohort, identified from 76% (2.4 million) of the Welsh population, of continuously treated asthma patients between 2013 and 2017 using anonymised, person-level, linked, routinely collected primary and secondary care data in the Secure Anonymised Information Linkage (SAIL) Databank. We investigated the association between asthma-related health service utilisation, prescribing, and deaths with the 2011 Welsh Index of Multiple Deprivation (WIMD) and its domains. We studied 106,926 patients (534,630 person-years), 56.3% were female, with mean age of 47.5 years (SD = 20.3). Compared to the least deprived patients, the most deprived patients had slightly fewer total asthma-related primary care consultations per patient (incidence rate ratio IRR = 0.98, 95% CI 0.97-0.99, p-value < 0.001), slightly fewer routine asthma reviews (IRR = 0.98, 0.97-0.99, p-value < 0.001), lower controller-to-total asthma medication ratios (AMRs; 0.50 versus 0.56, p-value < 0.001), more asthma-related accident and emergency (A&E) attendances (IRR = 1.27, 1.10-1.46, p-value = 0.001), more asthma emergency admissions (IRR = 1.56, 1.39-1.76, p-value < 0.001), longer asthma-related hospital stay (IRR = 1.64, 1.39-1.94, p-value < 0.001), and were at higher risk of asthma-related death (risk ratio of deaths with any mention of asthma 1.56, 1.18-2.07, p-value = 0.002). Study limitations include the deprivation index being area based and the potential for residual confounders and mediators.
In this study, we observed that the most deprived asthma patients in Wales had different prescribing patterns, more A&E attendances, more emergency hospital admissions, and substantially higher risk of death. Interventions specifically designed to improve treatment and outcomes for these disadvantaged groups are urgently needed.
Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday ...functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme. Individualised semi-structured interviews with 33 adults (29 female; 49 ± 10 years; 6–11 months post-infection) explored expectations of IMT prior to the intervention, and post intervention interviews explored perceptions of IMT and its impact on recovery. Inductive thematic analysis was used to analyse the data. IMT helped many to feel proactive in managing their symptoms and was associated with perceived improvements in respiratory symptoms, exercise and work capacity, and daily functioning. IMT was well perceived and offers significant potential for use as part of a holistic recovery programme, although it is important to consider the complex, varied symptoms of post COVID-19, necessitating an individually tailored rehabilitation approach.
We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective ...protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments. Those patients with gene variants responsive to CFTR modulators may have found these therapies to be transformational; research is now focusing on safely reducing the burden of symptom-directed treatment. However, modulators are not available in all parts of the globe, an issue which is further widening existing health inequalities. For patients who are not suitable for- or do not have access to- modulator drugs, alternative approaches are progressing through the trials pipeline. There will be challenges encountered in design and implementation of these trials, for which the established global CF infrastructure is a major advantage. Here, the Cystic Fibrosis National Research Strategy Group of the UK NIHR Respiratory Translational Research Collaboration looks to the future of cystic fibrosis therapies and consider priorities for future research and development.
The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic's impact on people with chronic obstructive pulmonary disease (COPD) remains ...poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments.
Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations.
Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81).
The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.
The COVID-19 pandemic's impact on people with asthma is poorly understood. We hypothesised that lockdown restrictions were associated with reductions in severe asthma exacerbations requiring ...emergency asthma admissions and/or leading to death.
Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we compared weekly counts of emergency admissions and deaths due to asthma over the first 18 weeks in 2020 with the national averages over 2015-2019. We modelled the impact of instigating lockdown on these outcomes using interrupted time-series analysis. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. We also investigated trends in asthma-related primary care prescribing and emergency department (ED) attendances in Wales.
Lockdown was associated with a 36% pooled reduction in emergency admissions for asthma (incidence rate ratio, IRR: 0.64, 95% CI: 0.49 to 0.83, p value 0.001) across both countries. There was no significant change in asthma deaths (pooled IRR: 0.57, 95% CI: 0.17 to 1.94, p value 0.37). ED asthma attendances in Wales declined during lockdown (IRR: 0.85, 95% CI: 0.73 to 0.99, p value 0.03). A large spike of 121% more inhaled corticosteroids and 133% more oral corticosteroid prescriptions was seen in Wales in the week before lockdown.
National lockdowns were associated with substantial reductions in severe asthma exacerbations leading to hospital admission across both Scotland and Wales, with no corresponding increase in asthma deaths.
Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet ...identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations--with a meta-analysis false discovery rate less than 10(-4)--between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.
Background Total IgE is a therapeutic target in patients with allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE levels in an epigenome-wide association ...study of white subjects. Whether DNA methylation of eosinophils explains these findings is insufficiently understood. Methods We tested for association between genome-wide DNA methylation in WBCs and total IgE levels in 2 studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL; n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II) study (n = 573). Whole-genome methylation of DNA from WBCs was measured by using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE levels were measured by using the UniCAP 100 system. In PR-GOAL WBC types (ie, neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured by using Coulter Counter techniques. In the GALA II study WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE levels, which was first conducted separately for each cohort, and then results from the 2 cohorts were combined in a meta-analysis. Results CpG sites in multiple genes, including novel findings and results previously reported in white subjects, were significantly associated with total IgE levels. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in the genes ZFPM1 ( P = 1.5 × 10−12 ), ACOT7 ( P = 2.5 × 10−11 ), and MND1 ( P = 1.4 × 10−9 ). Conclusions In an epigenome-wide association study adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE levels among Hispanic children.
To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause ...acute respiratory tract infection and covid 19.
Phase 3 open label randomised controlled trial.
United Kingdom.
6200 people aged ≥16 years who were not taking vitamin D supplements at baseline.
Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months.
The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat.
Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63).
Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.
ClinicalTrials.gov NCT04579640.
There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs ...of asthma.
We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010-11, and routine administrative, health and social care datasets for 2011-12; 2011-12 costs were estimated in pounds sterling using economic modelling.
The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7-31.3; n = 18.5 million (m) people) and 15.6 % (14.3-16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9-10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7-5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths.
Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs.
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