Showing papers by "Hana Müllerová published in 2022"
TL;DR: This work assessed how the presence/absence of specific TTs relate to the diagnosis and severity of ‘asthma’, ‘COPD’ or ‘ asthMA + COPd’.
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real‐world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of ‘asthma’, ‘COPD’ or ‘asthma + COPD’.
15 citations
TL;DR: Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion, illustrating that every exacerbation counts.
Abstract: Background Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes. Objective To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort. Methods Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up. Results Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66–1.74), 2.31 (95% CI 2.24–2.37), and 3.52 (95% CI 3.43–3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion. Conclusion Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.
10 citations
TL;DR: Although the underlying mechanisms are not fully elucidated, patients with COPD should be monitored for risk of CV outcomes after exacerbations and preventing exacerbations may decrease the risk of subsequent acute CV events.
Abstract: Background: The majority of patients with chronic obstructive pulmonary disease (COPD) suffer from comorbid cardiovascular (CV) disease. Accumulating evidence suggests a temporal association between COPD exacerbations and acute CV events, possibly due to lung hyperinflation, increased hypoxemia and systemic inflammation. The aims of the study were to estimate the risk of (1) acute CV events [acute myocardial infarction (AMI), CV-related death] or stroke in the months following a COPD exacerbation and (2) COPD exacerbation in the months following an acute CV event. Methods: A systematic literature review of observational studies published since 2000 was conducted by searching literature databases (Medline and Embase). Studies were eligible if conducted in adults with COPD, exposed to either COPD exacerbation or acute CV events, with outcomes of acute CV events or COPD exacerbation reported. Studies were appraised for relevance, bias and quality. Meta-analyses, using random-effect models, were performed for each outcome of interest, thus providing a pooled relative risk (RR) and its 95% confidence interval. Results: Eight studies were identified, of which seven were used for the meta-analyses examining the risk of CV events 1–3 months after an exacerbation compared with none. For stroke (six studies), RR was 1.68 (95% CI = 1.19–2.38). For AMI (six studies), RR was 2.43 (95% CI = 1.40–4.20). No studies exploring risk of exacerbation following an acute CV event were identified. Conclusion: This meta-analysis identified a markedly increased risk of stroke or AMI within a relatively short period of time following a COPD exacerbation. Although the underlying mechanisms are not fully elucidated, patients with COPD should be monitored for risk of CV outcomes after exacerbations. In addition, preventing exacerbations may decrease the risk of subsequent acute CV events. Registration: The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42020211055).
6 citations
TL;DR: In this article , the authors aimed to describe the clinical and healthcare resource utilisation burden of physician-assessed mild asthma using the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329).
Abstract: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma.Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits.Overall, 2004 patients with mild asthma were included; 22.8% experienced ≥1 exacerbation in the previous 12 months, of whom 72.3% experienced ≥1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation ± 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score <20), increasing to 55.6% for those with ≥2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring ≥1 emergency department visit and 1.1% requiring ≥1 hospital admission.In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.
5 citations
TL;DR: Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months by as mentioned in this paper , and was associated with adverse clinical outcomes across asthma and COPD.
Abstract: Persistent cough with sputum production is an important clinical trait in chronic obstructive pulmonary disease (COPD). We defined "frequent productive cough" based on 2 questions from the St George's Respiratory Questionnaire (SGRQ) and sought to determine its occurrence and associated outcomes in patients with physician-assigned asthma and/or COPD from the NOVELTY study.Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months (scoring ≥3 for both SGRQ questions). Relationships with baseline disease characteristics and exacerbations over 12 months' follow-up were examined using logistic regression.Baseline SGRQ data were available for 7125 patients, of whom 31.3% had frequent productive cough. It was more common in asthma+COPD (38.8%) and COPD (38.1%) than asthma (25.0%), increasing with physician-assessed severity, and in current versus former and never smokers. Patient-reported symptomatic worsening was more common in patients with versus without frequent productive cough. Reduced post-bronchodilator FEV1 (odds ratio [OR] per 10% decrement 1.14 [95% confidence interval 1.11-1.16]) and history of pollutant exposure at home/work (OR 1.50 [1.33-1.69]) were associated with frequent productive cough in all diagnoses. Patients with baseline frequent productive cough were more likely to have ≥1 exacerbation over the subsequent 12 months (OR 1.71 [1.52-1.93]), including exacerbations requiring hospital admission and those treated with oral corticosteroids.Frequent productive cough represents an important indicator of adverse clinical outcomes across asthma and/or COPD. Research into the underlying pathologic mechanisms is required to support targeted therapy development.GOV: NCT02760329.
4 citations
TL;DR: In this article , negative binomial regression modelled the association between baseline LRTIs and subsequent COPD exacerbations and Cox proportional hazard regression was used to investigate mortality in 215 234 patients with COPD.
Abstract: Objective Little is known about how lower respiratory tract infections (LRTIs) before chronic obstructive pulmonary disease (COPD) are associated with future exacerbations and mortality. We investigated this association in patients with COPD in England. Methods Clinical Practice Research Datalink Aurum, Hospital Episode Statistics and Office of National Statistics data were used. Start of follow-up was patient’s first ever COPD diagnosis date and a 1-year baseline period prior to start of follow-up was used to find mild LRTIs (general practice (GP) events/no antibiotics), moderate LRTIs (GP events+antibiotics) and severe LRTIs (hospitalised). Patients were categorised as having: none, 1 mild only, 2+ mild only, 1 moderate, 2+ moderate and 1+ severe. Negative binomial regression modelled the association between baseline LRTIs and subsequent COPD exacerbations and Cox proportional hazard regression was used to investigate mortality. Results In 215 234 patients with COPD, increasing frequency and severity of mild and moderate LRTIs were associated with increased rates of subsequent exacerbations compared with no recorded LRTIs (1 mild adjusted IRR 1.16, 95% CI 1.14 to 1.18, 2+ mild IRR 1.51, 95% CI 1.46 to 1.55, 1 moderate IRR 1.81, 95% CI 1.78 to 1.85, 2+ moderate IRR 2.55, 95% CI 2.48 to 2.63). Patients with 1+ severe LRTI (vs no baseline LRTIs) also showed an increased rate of future exacerbations (adjusted IRR 1.75, 95% CI, 1.70 to 1.80). This pattern of association was similar for risk of all-cause and COPD-related mortality; however, patients with 1+ severe LRTIs had the highest risk of all-cause and COPD mortality. Conclusion Increasing frequency and severity of LRTIs prior to COPD diagnosis were associated with increasing rates of subsequent exacerbations, and increasing risk of all-cause and COPD-related mortality.
3 citations
01 May 2022
2 citations
TL;DR: In this paper , the authors explored the association between pre-COPD diagnosis LRTIs and post-diagnosis exacerbations and mortality, and found that LRTI prior to diagnosis is indicative of worse COPD outcomes.
Abstract: Background: Lower respiratory tract infections (LRTIs) before COPD diagnosis may be a risk factor for higher COPD burden. Aims: To explore the association between pre-COPD diagnosis LRTIs and post-COPD diagnosis exacerbations and mortality. Methods: An observational UK cohort study was conducted using CPRD linked with hospitalisations and death statistics. People with a first-ever COPD diagnosis between 2004-2019 were included. LRTIs were mild (GP visit + no antibiotics), moderate (GP + antibiotics), or severe (hospitalisation). Six mutually-exclusive exposure groups were: no LRTI, 1 mild, 2+ mild, 1 moderate, 2+ moderate, 1+ severe 12 months preceding inclusion. Post-COPD diagnosis outcomes were (i) number of exacerbations, (ii) death due to any cause, COPD or cardiovascular disease (CVD). Poisson regression models adjusted on baseline confounders were used. Results: 215,234 patients were included. Compared with no LRTI (ref), patients with 1 moderate (IRR 1.9; 95%CI 1.9-1.9), 2+ moderate (IRR 2.6; 95%CI 2.6-2.6), or 1+ severe (IRR 1.2; 95% CI 1.2-1.2) LRTIs were at increased risk of exacerbation. All-cause mortality was increased in patients with 1 moderate (IRR 1.3; 95%CI 1.2-1.3), 2+ moderate (IRR 1.4; 95%CI 1.3-1.4), or 1+ severe (IRR 1.3; 95% CI 1.2-1.3) LRTIs. Similar results were found for COPD mortality. Only moderate LRTIs were associated with increased CVD mortality. Mild events were inconsistently associated with outcomes. Conclusion: LRTIs prior to diagnosis are indicative of worse COPD outcomes. This may offer an opportunity for disease modification through prompt diagnosis and pro-active management.
1 citations
04 Sep 2022
TL;DR: In this article , the authors measured possible associations between COPD-related OCS use or cumulative OCS exposure and all-cause mortality (ACM) in patients with COPD.
Abstract: Background: Oral corticosteroids (OCS) are sometimes used to manage exacerbations of chronic obstructive pulmonary disease (COPD). However, their use has been associated with adverse outcomes such as mortality. Aim: To measure possible associations between COPD-related OCS use or cumulative OCS exposure and all-cause mortality (ACM) in patients with COPD. Methods: This historical, observational cohort study used the UK Clinical Practice Research Datalink (1987−2019) linked to mortality data to compare patients who ever (OCS group) or never (non-OCS group) used OCS. Patients with a COPD diagnosis on/after 1 April 2003 were identified. Direct matching was performed between the OCS group (index date: first COPD-related OCS prescription) and non-OCS group (index date: nearest primary care visit to a matched OCS patient). Cox regressions examined associations between OCS use or time-varying cumulative OCS exposure and ACM, adjusted for confounders that included baseline exacerbation number. Results: Of 323,722 patients with COPD identified, 106,775 received COPD-related OCS (median follow-up, 7.8 years); 53,299 pairs were able to be matched (mean ± SD age, 64.6±12.5 years; 59.8% male). Compared with the non-OCS group, the OCS group had higher ACM risk (adjusted hazard ratio [HR] [95% CI]: 1.03 [1.00, 1.06]). Relative to cumulative OCS exposure <0.5g, cumulative exposure ≥0.5g was associated with higher ACM risk (adjusted HR [95% CI]: 0.5−<1.0g, 1.74 [1.65, 1.83]; 1.0−<2.5g, 2.45 [2.33, 2.58]; 2.5−<5.0g, 3.26 [3.08, 3.45]; 5.0−<10.0g, 4.01 [3.77, 4.27]; ≥10.0g, 5.75 [5.39, 6.13]). Conclusion: OCS use was associated with a higher risk of all-cause mortality, which increased with higher cumulative OCS exposure.
04 Sep 2022
TL;DR: In this article , the authors evaluated the temporality of the association between FPC and subsequent COPD exacerbations and found that FPC is associated with greater asthma and/or COPD severity and exacerbation risk.
Abstract: Background: Frequent productive cough (FPC) is associated with greater asthma and/or COPD severity and exacerbation risk. Aim: To evaluate the temporality of the association between FPC and subsequent COPD exacerbations. Methods: In patients with physician-assigned COPD diagnosis without concomitant asthma from NOVELTY (NCT02760329), FPC at baseline was defined as SGRQ scores ≥3 for cough and sputum (symptoms most/several days/week for past 3 months). Exacerbations (0 vs ≥1) were assessed quarterly for 1 year. The relationship between FPC and exacerbations was assessed by a repeated measures binomial model, adjusted for age, sex and smoking status. To test for any difference in trajectory between FPC status and exacerbation risk per quarter, an interaction term was applied. Results: Of 2,123 patients with COPD (mean age 67.2 [SD 9.0] years, 38% female, mean post-BD FEV1 61% [SD 23%] predicted), 36% had FPC at baseline. Mean exacerbation risk was 0.65 vs 0.44 events/person/year in patients with vs without FPC. In each quarter, exacerbation risk was consistently higher in patients with vs without FPC (OR 1.72 [95% CI 1.44, 2.06]), following a similar trajectory (p=0.6991; Figure). Conclusions: Frequent productive cough was consistently associated with higher COPD exacerbation risk over the first 4 quarters of follow-up, suggesting that it can be considered as a trait related to exacerbation risk.
01 Nov 2022
TL;DR: In this paper , the authors compared the use of OCS and non-OCS in patients with chronic obstructive pulmonary disease (COPD) and found that OCS use is associated with increased HCRU and costs with a positive dose-response relationship.
Abstract:
Introduction and Objectives
Oral corticosteroids (OCS) are sometimes used to manage exacerbations in patients with chronic obstructive pulmonary disease (COPD). Evidence suggests chronic OCS use is related to adverse outcomes, which may be associated with additional healthcare resource utilisation (HCRU) and costs. The objective of this study was to compare HCRU in patients who ever or never used OCS (OCS vs non-OCS cohorts) and to examine associations between cumulative OCS exposure and HCRU/costs.Methods
This matched historical observational cohort study used the UK Clinical Practice Research Datalink (1987–2019). Patients with a COPD diagnosis on/after 1 April 2003 and Hospital Episode Statistics linkage were included. Attendances for emergency room, specialist or primary care (PC) outpatient and inpatient visits were analysed. Costs were estimated using Health and Social Care 2019 and NHS Reference Costs 2019–2020 reports.Results
Compared with the non-OCS cohort, the OCS cohort had higher annualised total attendances and costs (table 1). Compared with patients with cumulative OCS doses <0.5 g, patients with higher cumulative doses had higher costs (incidence rate ratios; 95% CI) starting at 0.5–<1.0 g for specialist consultations (1.91; 1.89, 1.93), inpatient non-elective short stays (1.10; 1.09, 1.12) and long stays (1.039; 1.036, 1.042) and PC consultations (1.274; 1.267, 1.281).Conclusions
OCS use is associated with increased HCRU and costs, with a positive dose-response relationship. Please refer to page A216 for declarations of interest related to this abstract.04 Sep 2022
TL;DR: In this article , a negative binomial regression model was used to evaluate the relationship between SGRQ at baseline and exacerbations at 1-year follow-up in patients with a physician-assigned COPD diagnosis.
Abstract: Background: In clinical studies, poorer COPD health status is associated with increased exacerbation risk. Aim: To evaluate this relationship in a global cohort of patients with a physician-assigned COPD diagnosis. Methods: Patients with a physician-assigned COPD diagnosis without concomitant asthma from NOVELTY (NCT02760329), recruited from primary (46%) and secondary care, were included. Health status was assessed using baseline SGRQ total score; physician-reported exacerbations were collected at 1-year follow-up. A negative binomial regression model assessed the relationship between SGRQ at baseline and exacerbations (adjusted for age, sex, smoking status, prior exacerbations) at 1-year follow-up. Results: Of 2,123 patients with COPD (mean age 67.2 [SD 9.0] years, 38% female, mean post-BD FEV1 61% [SD 23%] predicted), 74% had SGRQ total score ≥25 at baseline (overall mean 40.6 [SD 21.6]). At 1-year follow-up, mean exacerbation risk was 0.51, 1.67, 0.62 and 0.21 events/patient/year in patients overall, with ≥1 event, with SGRQ total score ≥25 and with SGRQ total score <25, respectively. A 4-point increase in baseline SGRQ total score was associated with a 6% increase in 1-year exacerbation risk (relative risk: 1.06; 95% CI 1.05, 1.08; p<0.001). Conclusions: In this real-world population of patients with COPD, predominantly with mild/moderate airflow limitation, with a large proportion from primary care, exacerbation risk increased with poorer baseline COPD health status, independent of age, sex, smoking status and prior exacerbations. Patients with higher symptom burden should be considered for treatment optimisation to reduce their risk of future exacerbations.
04 Sep 2022
TL;DR: In this paper , the authors explored predictors for corticosteroid- and antibiotic only-treated attacks in the multi-country, prospective, observational NOVELTY cohort (NCT02760329).
Abstract: Background: Risk factors for asthma attacks requiring corticosteroid treatment include elevated biomarkers of type-2 airway inflammation. In real life, asthma attacks are often treated with antibiotics, and little is known about these attacks. Aim: We explored predictors for corticosteroid- and antibiotic only-treated attacks in the multi-country, prospective, observational NOVELTY cohort (NCT02760329). Methods: Patients with physician-assigned asthma with baseline data for 15 candidate predictors (including blood eosinophils [EOS] and fractional exhaled nitric oxide [FeNO]) and data for exacerbation history (acute asthma requiring ≥3 days of corticosteroids and/or hospitalisation, or antibiotics only) in the 12 months prior to and the 12 months post-baseline, not on biologics, were included. Adjusted rate ratios [95% confidence intervals] were calculated to determine risk factors for annualised corticosteroid- and antibiotic only-treated attacks. Results: Of 4,753 patients with asthma, 961 with full predictors and outcomes data were included. Significant predictors for corticosteroid-treated attacks were female sex (1.54 [1.08–2.21]), increased symptoms (Asthma Control Test 0.94 [0.91–0.97], for one unit) and a prior corticosteroid-treated attack (3.68 [2.69–5.03]); but not EOS and FeNO. Predictors for antibiotic only-treated attacks were low FEV1% (0.98 [0.96–1.00], for one unit), comorbid rhinosinusitis (2.42 [0.98–5.93]) and a prior antibiotic only-treated attack (4.24 [1.53–12.07]). Conclusion: Risk factors for corticosteroid- and antibiotic only-treated attacks differed. Contrary to clinical trial reports, type-2 biomarkers did not predict asthma attacks in this subset of patients.