Health and cost impact of stepping-down asthma medication for UK patients, 2001-2017:A population-based observational study

BackgroundGuidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs.Methods and findingsWe used nationwide UK primary care medical records, 2001-2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting β2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (adjusted hazard ratio, 95% CI, p-value: ICS inhaler dose = 0.86, 0.77-0.93, p ConclusionIn this UK study, we observed that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses. Stepping down medication did not adversely affect outcomes and was associated with substantial cost savings

Low uptake of palliative care for COPD patients within primary care in the UK

Mortality and symptom burden from chronic obstructive pulmonary disease (COPD) and lung cancer are similar but there is thought to be an inequality in palliative care support (PCS) between diseases. This nationally representative study assessed PCS for COPD patients within primary care in the UK.This was a cohort study using electronic healthcare records (2004-2015). Factors associated with receiving PCS were assessed using logistic regression for the whole cohort and deceased patients.There were 92 365 eligible COPD patients, of which 26 135 died. Only 7.8% of the whole cohort and 21.4% of deceased patients received PCS. Lung cancer had a strong association with PCS compared with other patient characteristics, including Global Initiative for Chronic Obstructive Lung Disease stage and Medical Research Council Dyspnoea score (whole cohort, lung cancer: OR 14.1, 95% CI 13.1-15; deceased patients, lung cancer: OR 6.5, 95% CI 6-7). Only 16.7% of deceased COPD patients without lung cancer received PCS compared with 56.5% of deceased patients with lung cancer. In patients that received PCS, lung cancer co-diagnosis significantly increased the chances of receiving PCS before the last month of life (1-6 versus ≤1 month pre-death: risk ratio 1.4, 95% CI 1.3-1.7).Provision of PCS for COPD patients in the UK is inadequate. Lung cancer, not COPD, was the dominant driver for COPD patients to receive PCS

Changing causes of death for patients with chronic respiratory disease in England, 2005-2015

Background: Chronic respiratory diseases (CRD) are common, increasing in prevalence, and cause significant morbidity and mortality worldwide. However, we have limited knowledge on causes of death of patients with CRD in the general population. Objective: We evaluated mortality rates and causes of death over time in CRD patients.Methods: We used linked primary care and mortality data to determine mortality rates and the most common causes of death in people with CRD (including asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD)) during 2005-2015 in England. Results: We identified 558,888 CRD patients (451,830 asthma, 137,709 COPD, 19,374 bronchiectasis, 10,745 ILD). The age-standardised mortality rate of patients with CRD was 1,607 per 100,000 persons (asthma=856, COPD=1,503, ILD=2,609, bronchiectasis=1,463). CRD mortality was overall 54% higher than the general population. One third of CRD patients died from respiratory-related causes. Respiratory-related mortality was constant, while cardiovascular-related mortality decreased significantly over time. COPD accounted for the majority of respiratory-related deaths (66% overall) in all patient groups except ILD. Conclusions: CRD patients continue to experience substantial morbidity and mortality due to respiratory diseases. Disease-modifying intervention strategies are needed to improve outcomes for patients with CRD

Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy

Rationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually . Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. METHODS: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. RESULTS: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. CONCLUSIONS: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response

Clinical profile of predefined asthma phenotypes in a large cohort of UK primary care patients (Clinical Practice Research Datalink).

BACKGROUND: Distinct asthma phenotypes have previously been suggested, including benign asthma, atopic asthma and obese non-eosinophilic asthma. This study aims to establish if these phenotypes can be identified using data recorded in primary care clinical records and reports on patient characteristics and exacerbation frequency. METHODS: A population-based cohort study identified 193,999 asthma patients in UK primary care from 2007 to 2017. We used linked primary and secondary care data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Patients were classified into predefined phenotypes or included in an asthma "not otherwise specified" (NOS) group. We used negative binomial regression to calculate the exacerbation rates and adjusted rate ratios. Rate ratios were further stratified by asthma treatment step. RESULTS: In our cohort, 3.9% of patients were categorized as benign asthma, 28.6% atopic asthma and 4.8% obese non-eosinophilic asthma. About 62.7% of patients were asthma NOS, including asthma NOS without treatment (10.4%), only on short-acting beta agonist (6.1%) and on maintenance treatment (46.2%). Crude severe exacerbation rates per 1,000 person-years were lowest for benign asthma (106.8 [95% CI: 101.2-112.3]) and highest for obese non-eosinophilic asthma (469.0 [451.7-486.2]). Incidence rate ratios for all phenotype groups decreased when stratified by treatment step but remained raised compared to benign asthma. CONCLUSION: Established phenotypes can be identified in a general asthma population, although many patients did not fit into the specific phenotypes which we studied. Phenotyping patients and knowledge of asthma treatment step could help anticipate clinical course and therefore could aid clinical management but is only possible in a minority of primary care patients based on current phenotypes and electronic health records (EHRs)

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population

Background: Excessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. Methods: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3–6, 7–10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. Results: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3–6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7–10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). Conclusions: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong

Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19 a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

BackgroundStudies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.MethodsWe analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (Findings75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16-49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16-49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05-1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08-1·27]; pInterpretationUnderlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease.FundingNational Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

Rationale: New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives: To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods: We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results: An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions: Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment

Clinical profile of predefined asthma phenotypes in a large cohort of UK primary care patients

Abstract: Background: Distinct asthma phenotypes have previously been suggested, including benign asthma, atopic asthma and obese non-eosinophilic asthma. This study aims to establish if these phenotypes can be identified using data recorded in primary care clinical records and reports on patient characteristics and exacerbation frequency. Methods: A population-based cohort study identified 193,999 asthma patients in UK primary care from 2007 to 2017. We used linked primary and secondary care data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Patients were classified into predefined phenotypes or included in an asthma “not otherwise specified” (NOS) group. We used negative binomial regression to calculate the exacerbation rates and adjusted rate ratios. Rate ratios were further stratified by asthma treatment step. Results: In our cohort, 3.9% of patients were categorized as benign asthma, 28.6% atopic asthma and 4.8% obese non-eosinophilic asthma. About 62.7% of patients were asthma NOS, including asthma NOS without treatment (10.4%), only on short-acting beta agonist (6.1%) and on maintenance treatment (46.2%). Crude severe exacerbation rates per 1,000 person-years were lowest for benign asthma (106.8 [95% CI: 101.2–112.3]) and highest for obese non-eosinophilic asthma (469.0 [451.7–486.2]). Incidence rate ratios for all phenotype groups decreased when stratified by treatment step but remained raised compared to benign asthma. Conclusion: Established phenotypes can be identified in a general asthma population, although many patients did not fit into the specific phenotypes which we studied. Phenotyping patients and knowledge of asthma treatment step could help anticipate clinical course and therefore could aid clinical management but is only possible in a minority of primary care patients based on current phenotypes and electronic health records (EHRs)