Publications
108 results found
Price LC, Kouranos V, Baughman R, et al., 2024, Use of pulmonary arterial hypertension therapies in patient swith sarcoidosis-associated pulmonary hypertension., Sarcoidosis Vasc Diffuse Lung Dis, Vol: 41
Melén E, Faner R, Allinson JP, et al., 2024, Lung-function trajectories: relevance and implementation in clinical practice, The Lancet, ISSN: 0140-6736
Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.
Khalaf Z, Bush A, Saglani S, et al., 2024, Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma, Thorax, Vol: 79, Pages: 112-119, ISSN: 0040-6376
Background Asthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and exacerbations.Methods Primary care medical records, 2004–2021, were linked to hospital records. Children were categorised by age at diagnosis and followed until the next age bracket. Ages (based on management guidelines) were 5–8 years, 9–11 years and adolescents (12–16 years). Characteristics evaluated included body mass index, allergies and events before and after diagnosis (symptoms, medication). Exacerbation incidence was calculated. Multivariable Cox proportional hazards determined associations with exacerbations.Results 119 611 children were eligible: 61 940 (51.8%) 5–8 years, 32 316 (27.7%) 9–11 years and 25 355 (21.2%) adolescents. Several characteristics differed by age; children aged 5–8 years had the highest proportion with eczema, food/drug allergy and cough, but adolescents had the highest proportion with overweight/obesity, aeroallergen sensitisation, dyspnoea and short-acting-beta-agonist only use. Exacerbation rates were highest in the youngest children (per 100 person-years (95% CI): 5–8 years =13.7 (13.4–13.9), 9–11 years =10.0 (9.8–10.4), adolescents =6.7 (6.5–7.0)). Exacerbation risk factors also differed by age; 5–8 years: male, eczema and food/drug allergy were strongly associated, but for children ≥9 years old, obesity and aeroallergen sensitisation were strongly associated. For all children, higher socioeconomic deprivation was significantly associated with having an exacerbation. Delayed diagnosis was most common in children aged 5–8 years and was associated with increased exacerbations across all ages.Conclusion Children’s baseline characteristics and exacerbation rates varied according to their age group. Clinica
Ritchie AI, Donaldson GC, Hoffman EA, et al., 2024, Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry., Am J Respir Crit Care Med
RATIONALE: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. OBJECTIVES: We hypothesised that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. METHODS: We recruited 431 current smokers (median age 39 years, 16 pack-years smoked) and recorded symptoms by the COPD Assessment Test (CAT), spirometry and quantitative thoracic CT (QCT) scans at study entry. These scans results were compared to 67 never smoking controls. 368 participants were followed every six months with measurement of post-bronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age and sex was related to the initial QCT appearances and symptoms, measured with the CAT. MEASUREMENTS AND MAIN RESULTS: There were no material differences in demography or subjective CT appearances between the young smokers and controls, but 55.7% of the former had a CAT score above 10 and 24.2% reported chronic bronchitis. QCT assessments of Disease Probability-defined functional small airways disease, ground glass opacification, bronchovascular prominence and small blood vessel to total pulmonary vessel volume ratio were increased compared to controls and were all associated with a faster FEV1 decline as was a higher CAT score. CONCLUSIONS: Radiologic abnormalities on CT are already established in young smokers with normal lung function and is associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Valencia-Hernández CA, Del Greco M F, Sundaram V, et al., 2023, Asthma and incident coronary heart disease: an observational and Mendelian randomisation study, European Respiratory Journal, Vol: 62, ISSN: 0903-1936
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.First, we conducted an observational study using U.K. medical records to match asthma patients, by age, sex and GP practice, 1:1 to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian Randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium, and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium. Using 64 asthma SNPs, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.In our observational study (N=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR=1.06, 95%CI=1.01-1.13), after accounting for healthcare behaviour, we found no association (model 2: HR=0.99, 95% CI=0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR=1.11, 95%CI=1.01-1.21; males: HR=0.91, 95%CI=0.84-0.98). Our MR study (N=589 875) found no association between asthma and CHD (OR=1.01; 95%CI=0.98-1.04) and no modification by sex.Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Bloom CI, Adcock IM, 2023, CC16: a treatable trait in asthma?, American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 745-746, ISSN: 1073-449X
Ritchie AI, Singayagam A, Mitchell S, et al., 2023, The effect of inhaled corticosteroids on pneumonia risk in patients with COPD-bronchiectasis overlap: a UK population-based case-control study, Chest, Vol: 164, Pages: 875-884, ISSN: 0012-3692
BackgroundInhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and are commonly used in patients with COPD-bronchiectasis overlap.Research QuestionIs the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis?Study Design and MethodsElectronic healthcare records (2004-2019) were used to obtain a cohort of COPD patients and a nested case-control (age-gender matched 1:4). Analyses were conducted to determine the risk of hospitalised pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control, containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BEC), was used to determine any association with BEC.Results316,663 were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (AHR=1.24, 95% CI 1.15-1.33). In the first nested case-control of 84,316 COPD patients, ICS was found to increase the odds of pneumonia (AOR=1.26, 95% CI 1.19-1.32), only if used in the previous 180 days. However, bronchiectasis was a significant modifier such that ICS use did not further augment the already elevated bronchiectasis-associated pneumonia risk (AOR, 95% CI: COPD-bronchiectasis=1.01, 0.8-1.28; no bronchiectasis=1.27, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control, confirmed these findings. Lastly, we found BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was significantly associated with pneumonia (AOR, 95% CI: BEC≤3x109/L=1.56, 1.05-2.31, BEC>3x109/L=0.89, 0.53-1.24).InterpretationICS use does not further augment the already increased risk of hospitalised pneumonia associated with concomitant bronchiectasis in COPD.
Lo CWH, Pathadka S, Qin SX, et al., 2023, Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review., Eur Respir Rev, Vol: 32
BACKGROUND: The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown. OBJECTIVE: To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma. METHODS: A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded. RESULTS: 59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10th revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children. CONCLUSION: Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.
Bloom C, 2023, Covid‐19 pandemic and asthma: what did we learn?, Respirology, Vol: 28, Pages: 603-614, ISSN: 1323-7799
This review addresses some of the major lessons we have learnt regarding asthma and the covid-19 pandemic, including susceptibility to SARS-CoV-2 infection and severe covid-19, potentially protective factors, comparison to other respiratory infections, changes in healthcare behaviour from the perspective of patients and clinicians, medications to treat or prevent covid-19, and post-covid syndrome.
Khalaf Z, Saglani S, Bloom CI, 2022, CHARACTERISING SCHOOL-AGE CHILDREN WITH ASTHMA: ENGLISH POPULATION-COHORT STUDY, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A23-A23, ISSN: 0040-6376
Valencia-Hernandez CA, Zakeri R, Sundaram V, et al., 2022, INCREASED RISK OF CARDIOVASCULAR DISEASE IN ASTHMA, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A47-A48, ISSN: 0040-6376
Ritchie AI, Singanayagam A, Mitchell S, et al., 2022, THE RISK OF PNEUMONIA IN COPD PATIENTS WITH CONCOMITANT BRONCHIECTASIS USING INHALED CORTICOSTEROIDS: A UK CASE-CONTROL STUDY, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A70-A70, ISSN: 0040-6376
Price LC, Garfield B, Bloom C, et al., 2022, Persistent isolated impairment of gas transfer following COVID-19 pneumonitis relates to perfusion defects on dual-energy computed tomography, ERJ Open Research, Vol: 8, Pages: 1-5, ISSN: 2312-0541
Conway FM, Bloom CI, Shah PL, 2022, Susceptibility of patients with airways disease to SARS-CoV-2 infection., American Journal of Respiratory and Critical Care Medicine, Vol: 206, Pages: 696-703, ISSN: 1073-449X
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic. People with airways disease are at higher risk of respiratory infection, and viruses can trigger respiratory exacerbations. Patients with airways disease may therefore be more susceptible to SARS-CoV-2 infection, development of covid-19, or be at higher risk of adverse outcomes. Here we review susceptibility, based on current epidemiological studies, and explore biological mechanisms. Evidence from multiple large observational studies has shown chronic obstructive pulmonary disease (COPD) is a significant risk factor for covid-19 related mortality. Whether people with asthma are more susceptible to infection or severe outcomes has been much debated but appears to be related to their asthma phenotype and severity. To what extent these differences are biological or influenced by public health non-pharmacological interventions is difficult to quantify. Biological mechanisms that may influence susceptibility and adverse outcomes in airways disease include the increased expression of protein receptors enabling viral cell entry, dysfunctional epithelial airway immunity, type-2 inflammation and the use of inhaled corticosteroids. A better understanding of the susceptibility and mechanisms is essential for developing preventative and therapeutic strategies. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Bloom C, Montonen J, Jons O, et al., 2022, Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases, PULMONARY THERAPY, Vol: 8, Pages: 75-93, ISSN: 2364-1754
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Bloom C, Montonen J, Jons O, et al., 2022, First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases, PULMONARY THERAPY, Vol: 8, Pages: 57-74, ISSN: 2364-1754
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Sundaram V, Nagai T, Chiang C-E, et al., 2022, Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients, JOURNAL OF CARDIAC FAILURE, Vol: 28, Pages: 353-366, ISSN: 1071-9164
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Bloom C, Wong E, Hickman K, et al., 2021, Influence of the first wave of COVID-19 on asthma inhaler prescriptions, npj Primary Care Respiratory Medicine, Vol: 31, ISSN: 2055-1010
In the beginning of the COVID-19 pandemic there were major concerns regarding the huge demand for asthma inhalers. Using primary care medical records for 614,700 asthma patients between January and June 2020, we found that there was a substantial increase in inhalers solely in March 2020. Patients significantly associated with receiving higher inhaled corticosteroid prescriptions were younger, of higher socioeconomic status and had milder asthma.
Stewart I, Bloom C, 2021, Considerations for conducting and interpreting long-term follow-up of intervention studies: avoiding spoiled milk, Thorax, Vol: 76, Pages: 1067-1068, ISSN: 0040-6376
Bloom CI, Johnston SL, 2021, Decline in respiratory and cardiac admissions during the COVID-19 pandemic: what is the role of common respiratory virus infections?, Respirology, Vol: 26, Pages: 1010-1011, ISSN: 1323-7799
Numerous countries across the globe have introduced a variety of public health measures, non-pharmaceutical interventions (NPIs), to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and accordingly reduce coronavirus disease 2019 (COVID-19) hospitalizations and mortality. Effective NPIs have at the same time caused considerable changes in healthcare demand for non-COVID-19 conditions. In New Zealand, during the first wave of the pandemic in early 2020, their government instigated a stringent programme of restrictions, with a four-level alert system, including border closure, quarantine for returning travellers, social distancing measures and personal hygiene promotion. High public compliance with NPIs prevented COVID-19 community transmission for 102 consecutive days. In fact, they were so effective that the usual winter influenza surge was also disrupted, with an extraordinary 99.9% reduction in influenza virus detections as compared to previous years and a substantial reduction in all other respiratory viruses, including a 98% reduction in respiratory syncytial virus detections.1 Due to the key role viruses are known to play in many respiratory conditions and are postulated to play in myocardial infarctions and heart failure, it may be hypothesized that the stringent reductions implemented in New Zealand may also have mitigated the incidence of these conditions during that time.
Bloom CI, Cullinan P, Wedzicha JA, 2021, Asthma phenotypes and COVID-19 risk: a population-based observational study, American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 36-45, ISSN: 1073-449X
Rationale: Studies have suggested some asthma patients are at risk of severe COVID-19, but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives: Determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalisation rates to influenza and pneumonia. Methods: Electronic medical records were used to identify asthma patients and match them to the general population. Patient-level data were linked to Public Health England SARS-CoV-2 test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type-2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results: 434,348 asthma and 748,327 matched patients were included. All asthma patients had a significantly increased risk of a GP-diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (HR=1.27, 95%CI=1.01-1.61), intermittent ICS + add-on asthma medication use (HR=2.00, 95%CI=1.43-2.79), regular ICS + add-on use (HR=1.63, 95 CI=1.37-1.94), or with frequent exacerbations (HR=1.82, 95% CI=1.34-2.47) was significantly associated with hospitalisation. These phenotypes were significantly associated with influenza and pneumonia hospitalisations. Only patients with regular ICS + add-on asthma therapy (HR=1.70, 95%CI=1.27-2.26) or frequent exacerbations (HR=1.66, 95%CI=1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions: More severe asthma was associated with more severe COVID-19 outcomes, but type-2 inflammation was not. The risk of COVID-19 hospitalisation appeared to be similar to the risk with influenza or pneumonia.
Zakeri R, Morgan A, Sundaram V, et al., 2021, Under-recognition of heart failure in patients with atrial fibrillation and the impact of gender: a UK population-based cohort study, BMC Medicine, Vol: 19, ISSN: 1741-7015
Background: Patients with atrial fibrillation (AF) complicated by heart failure (HF) have a poor prognosis. We investigated whether long-term loop-diuretic therapy in patients with AF and no known diagnosis of HF, as a potential surrogate marker of undiagnosed HF, is also associated with worse outcomes.Methods: Adults with incident AF were identified from UK primary and secondary care records between 2004-2016. Repeat prescriptions for loop-diuretics, without a diagnosis of HF or documented non-cardiac indication, were classified as ‘isolated’ loop-diuretic use.Results: Amongst 124,256 people with incident AF (median 76 years, 47% women), 22,001 (17.7%) had a diagnosis of HF, and 22,325 (18.0%) had isolated loop-diuretic use. During 2.9 (LQ-UQ 1-6) years’ follow-up, 12,182 patients were diagnosed with HF (incidence rate 3.2 [95%CI 3.1-3.3]/100 person-years). Of these, 3,999 (32.8%) had prior isolated loop-diuretic use, including 31% of patients diagnosed with HF following an emergency hospitalisation. The median time from AF to HF diagnosis was 3.6 (1.2-7.7) years in men versus 5.1 (1.8-9.9) years in women (p=0.0001). In adjusted models, patients with isolated loop-diuretic use had higher mortality (HR 1.42 [95%CI 1.37-1.47], p<0.0005) and risk of HF hospitalisation (HR 1.60 [95%CI 1.42-1.80], p<0.0005) than patients with no HF or loop-diuretic use, and comparably poor survival to patients with diagnosed HFConclusions: Loop-diuretics are commonly prescribed to patients with AF and may indicate increased cardiovascular risk. Targeted evaluation of these patients may allow earlier HF diagnosis, timely intervention and better outcomes, particularly amongst women with AF, in whom HF appears to be under-recognised and diagnosed later than in men.
Altmann MC, Rinchai D, Baldwin N, et al., 2021, Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data, Nature Communications, Vol: 12, Pages: 1-19, ISSN: 2041-1723
As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/.
Bloom CI, Drake TM, Docherty AB, et al., 2021, 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, The Lancet Respiratory Medicine, Vol: 9, Pages: 699-711, ISSN: 2213-2600
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 (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma.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
Cook J, Bloom C, Lewis J, et al., 2021, Impact of health technology assessment on prescribing patterns of inhaled fixed-dose combination triple therapy in chronic obstructive pulmonary disease., J Mark Access Health Policy, Vol: 9, Pages: 1-10, ISSN: 2001-6689
Background: Evidence suggests that triple therapy for patients with chronic obstructive pulmonary disease (COPD) is being used in a broader range of patients than recommended by guidelines, which may have health and cost implications. Objective: To explore the relationship between national health technology assessment (HTA) agency appraisals and market penetration of two fixed-dose combination (FDC) triple therapies. Study design: HTAs from Q3 2017 to Q1 2020 from 10 countries were evaluated. Intervention: Glycopyrronium bromide/formoterol fumarate/beclomethasone (Trimbow®) and umeclidinium/vilanterol/fluticasone furoate (Trelegy™ Ellipta®). Main outcome measure: HTA restrictions and prescribing rates (days of therapy). Results: Seven countries (70%) imposed restrictions on use including prescription only for patients stable on free-combination triple therapy or not controlled on dual therapy, requirement of a specialist prescription or therapeutic plan, prescription only for patients with severe COPD, and use as second-line therapy or later. In general, countries that have imposed restrictions on the use of FDC triple therapies have seen a lower than average uptake. Conclusion: Payer guidance on prescribing FDC triple therapy may potentially support more appropriate prescribing in line with clinical guidelines. It is important for payers to consider which restrictions would ensure the most efficient use of scarce resources.
Bloom CI, Cullinan P, Wedzicha JA, 2021, Assessing Factors Associated with COVID19 Risk in Asthma, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Bloom C, Franklin C, Bush A, et al., 2021, Burden of preschool wheeze and progression to asthma in the UK: population-based cohort 2007 to 2017, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 1949-1958, ISSN: 0091-6749
BackgroundWheeze is one of the most common symptoms of preschool children (age 1 to 5 years), yet we have little understanding of the burden in the UK.ObjectivesDetermine prevalence and pattern of physician-confirmed preschool wheeze, related healthcare utilisation, and factors associated with progression to school-age asthma.MethodsWe used nationally representative primary and secondary care electronic medical records between 2007-2017 to identify preschool children with wheeze. Factors associated with asthma progression were identified in a nested cohort of children with follow-up from 1-2 years of age, until at least 8 years of age.ResultsFrom 1,021,624 preschool children, 69,261 were identified with wheeze. Prevalence of preschool wheeze was 7.7% in 2017. Wheeze events were lowest in August and highest in late-autumn/early-winter. During median follow-up of 2.0 years (IQR 1.2-4.0), 15.8% attended an emergency department, and 13.9% had a hospital admission, for a respiratory disorder. The nested cohort with prolonged follow-up identified 15,085 children; 35.5% progressed to asthma between 5-8 years old. Of children with preschool wheeze, without an asthma diagnosis, 34.9% were prescribed inhaled corticosteroids, and 15.6% oral corticosteroids. The factors most strongly associated with progression to asthma were wheeze frequency and severity, atopy, prematurity, maternal asthma severity and first reported wheeze event occurring in September.ConclusionsPreschool wheeze causes considerable healthcare burden, a large number of children are prescribed asthma medication and have unplanned secondary care visits. Multiple factors influence progression to asthma, including first wheeze event occurring in September.
Mallia P, Russell G, Meghji J, et al., 2021, Symptomatic, biochemical and radiographic recovery in patients with Covid-19, BMJ Open Respiratory Research, Vol: 8, ISSN: 2052-4439
Background: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described.Methods: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness.Results: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge.Conclusions: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.
Whittaker H, Bloom C, Morgan A, et al., 2021, Accelerated FEV1 decline and risk of cardiovascular disease and mortality in a primary care population of COPD patients, European Respiratory Journal, Vol: 57, ISSN: 0903-1936
Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD-GOLD) primary care dataset (n=36 282). Accelerated FEV1 decline was defined using the fastest quartile of the COPD population's decline. Cox regression assessed the association between baseline accelerated FEV1 decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease, and CVD mortality). The model was adjusted for age, gender, smoking status, BMI, history of asthma, hypertension, diabetes, statin use, mMRC dyspnoea, exacerbation frequency, and baseline FEV1 percent predicted.6110 (16.8%) COPD patients had a CVD event during follow-up; median length of follow-up was 3.6 years [IQR 1.7–6.1]). Median rate of FEV1 decline was –19.4 mL·year−1 (IQR, –40.5 to 1.9); 9095 (25%) patients had accelerated FEV1 decline (>–40.5 mL·year−1), 27 287 (75%) did not (≤ –40.5 mL·year−1). Risk of CVD and mortality was similar between patients with and without accelerated FEV1 decline (HRadj 0.98 [95%CI, 0.90–1.06]). Corresponding risk estimates were 0.99 (95%CI 0.83–1.20) for heart failure, 0.89 (95%CI 0.70–1.12) for myocardial infarction, 1.01 (95%CI 0.82–1.23) for stroke, 0.97 (95%CI 0.81–1.15) for atrial fibrillation, 1.02 (95%CI 0.87–1.19) for coronary artery disease, and 0.94 (95%CI 0.71–1.25) for CVD mortality. Rather, risk of CVD was associated with mMRC score ≥2 and ≥2 exacerbations in the year prior.CVD out
Naqvi SA, Patel R, Griffiths CJ, et al., 2021, P114 Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review, British Thoracic Society Winter Meeting, Publisher: BMJ Publishing Group, Pages: A151-A151, ISSN: 0040-6376
Background Oral corticosteroid (OCS) use increases the risk of systemic adverse effects including osteoporosis, fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if there is an increased risk of these adverse effects from inhaled corticosteroids (ICS) use in adults with asthma.Methods MEDLINE and EMBASE databases were searched to identify studies measuring adverse effects with ICS use in asthma, with those investigating a majority population of COPD patients excluded. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia, tuberculous or non-tuberculous mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and ROBINS-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies with the same outcome measurement.Results Thirteen studies met the inclusion criteria, two trials and eleven observational studies, all analysing the effects of ICS compared with non-ICS use for particular outcomes. Study outcomes by number of studies were: six BMD, six infection (four pneumonia, one tuberculous, one non-tuberculous mycobacterial), one ocular disorder (cataracts) and no diabetes. Studies addressing BMD were limited by study size, lack of generalisability, and short follow-up. BMD was measured from a range of bones via ultrasound or x-ray absorptiometry; most found a loss of BMD. Studies addressing infection suffered from lack of power, misclassification and selection bias; most studies found an increased risk of infection. Only one study assessed ocular disorders, they found an increased risk of cataracts. This study likely suffered from residual confounding. Most studies were unable to fully account for OCS exposure, total ICS exposure or difference between ICS drugs and their varyi
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