Risk Of Exacerbations In Patients Research Articles

Incremental long-term benefit of drug therapies for chronic obstructive pulmonary disease in quality of life but not mortality: a network meta-analysis

IntroductionThe latest evidence revealed that dupilumab, an interleukin-4 (IL-4) and interleukin-13 (IL-13) blocker, significantly reduces the exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). The efficacy of dupilumab compared with conventional inhaled drugs remains incompletely determined. This study aimed to investigate the comparative efficacy of dupilumab and conventional inhaled drugs in patients with stable COPD.Material and methodsThis study retrieved randomised clinical trials (RCTs) with follow-up ≥ 48 weeks on long-acting β-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), inhaled corticosteroids (ICSs), and dupilumab in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases. The information on eligible studies was extracted after the screening. The comparative efficacy of 4 drugs and their combinations in acute exacerbation and mortality was assessed using Bayesian network meta-analysis models.ResultsThis network meta-analysis identified 69 eligible RCTs on 7 classes of drug therapies after stepwise screening and included 125,331 COPD patients. Compared with placebo, the 7 drug interventions significantly reduced the risk of acute exacerbation, and the reduction degree increased with the incremental use of drug classes. ICS/LABA/LAMA/dupilumab was the most effective in decreasing exacerbation risk (OR = 0.561 [95% CI: 0.387–0.810]), followed by ICS/LABA/LAMA (OR = 0.717 [95% CI: 0.626–0.817]). The 7 drug therapies were not significantly associated with a lower risk of death compared to placebo. Nevertheless, ICS/LABA/LAMA/dupilumab is the most likely to be effective in decreasing mortality.ConclusionsThe incremental use of combinations of conventional and novel drugs contributed to the long-term benefits in acute exacerbation but not death in COPD. The optimal drug combination in terms of acute COPD exacerbation was ICS/LABA/LAMA/dupilumab.

Airsupra: An inhaled albuterol/budesonide combination for asthma.

The FDA has approved Airsupra (AstraZeneca), a metered-dose inhaler containing the short-acting beta2-agonist (SABA) albuterol and the inhaled corticosteroid (ICS) budesonide, for use as needed for treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients ≥18 years old with asthma. Airsupra is the first combination of a SABA and an ICS to become available in the US. It is not approved for use as maintenance therapy.

The six-minute step test can predict COPD exacerbations: a 36-month follow-up study

The six-minute step test (6MST) has been shown to be effective in assessing exercise capacity in individuals with COPD regardless of severity and, despite its easy execution, accessibility and validity, information on the prognostic power of this test remains uncertain. The aim of this study is to investigate whether the 6MST can predict the occurrence of exacerbations in patients with COPD. This is a prospective cohort study with a 36-month follow-up in patients with COPD. All patients completed a clinical assessment, followed by pulmonary function testing and a 6MST. The 6MST was performed on a 20 cm high step; heart rate, blood pressure, oxygen saturation, BORG dyspnea and fatigue were collected. Sixty-four patients were included in the study, the majority being elderly men. Performance on the 6MST demonstrated lower performance compared to normative values proposed in the literature, indicating a reduced functional capacity. Kaplan Meier analysis revealed that ≤ 59 steps climbed during the 6MST was a strong predictor of COPD exacerbation over a 36-month follow-up. We have identified a minimal threshold number of steps (≤ 59) obtained through the 6MST may be able predict the risk of exacerbations in patients with COPD.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β2-agonist (SABA) and inhaled corticosteroid (ICS) as alternative reliever at Step 2. The FDA approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and to reduce exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA–ICS during the window-of-opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that use of albuterol–budesonide rather than albuterol as reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the US. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.

Calcium Channel Blockers and the Risk of Exacerbation in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Study of 48,488 Outpatients.

Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker amlodipine. However, it remains unclear whether using this drug potentially affects the risk of acute severe exacerbations (AECOPD) and all-cause mortality in these patients. The data were collected from Danish national registries, containing complete information on health, prescriptions, hospital admissions, and outpatient clinic visits. The COPD patients (n = 48,488) were matched via propensity score on known predictors of the primary outcome in an active comparator design. One group was exposed to amlodipine treatment, and the other was exposed to bendroflumethiazide, since both of these drugs are considered to be the first choice for the treatment of arterial hypertension according to Danish guidelines. The use of amlodipine was associated with a reduced risk of death from all causes at the 1-year follow-up (hazard ratio 0.69, 95% confidence interval: 0.62-0.76) compared with the use of bendroflumethiazide in the matched patients. No difference in the risk of severe AECOPD was found. In the COPD patients, amlodipine use was associated with a lower risk of death from all causes compared with the use of bendroflumethiazide. Amlodipine seems to be a safe first choice for the treatment of arterial hypertension in COPD patients.

Modelling ASthma TrEatment Responses (MASTER): Effect of individual patient characteristics on the risk of exacerbation in moderate or severe asthma: A time-to-event analysis of randomized clinical trials.

There is limited understanding of how clinical and demographic characteristics are associated with exacerbation risk in patients with moderate-to-severe asthma, and how these factors correlate with symptom control and treatment response. Here we assess the relationship between baseline characteristics and exacerbation risk during regular dosing with inhaled corticosteroids (ICS) monotherapy or in combination with long-acting beta2-agonists (ICS/LABA) in clinical trial patients with varying levels of symptom control, as assessed by the asthma control questionnaire (ACQ-5). A time-to-event model was developed using pooled patient data (N = 16 282) from nine clinical studies [Correction added on 26 July 2023, after first online publication: The N value in the preceding sentence has been corrected in this version.]. A parametric hazard function was used to describe the time-to-first exacerbation. Covariate analysis included the assessment of the effect of seasonal variation, clinical and demographic baseline characteristics on baseline hazard. Predictive performance was evaluated by standard graphical and statistical methods. An exponential hazard model best described the time-to-first exacerbation in moderate-to-severe asthma patients. Body mass index, smoking status, sex, ACQ-5, % predicted forced expiratory volume over 1 s (FEV1 p) and season were identified as statistically significant covariates affecting baseline hazard irrespective of ICS or ICS/LABA use. Fluticasone propionate/salmeterol (FP/SAL) combination therapy resulted in a significant reduction in the baseline hazard (30.8%) relative to FP monotherapy. Interindividual differences at baseline and seasonal variation affect the exacerbation risk independently from drug treatment. Moreover, it appears that even when a comparable level of symptom control is achieved in a group of patients, each individual may have a different exacerbation risk, depending on their baseline characteristics and time of the year. These findings highlight the importance of personalized interventions in moderate-to-severe asthma patients.

Comparison of treatment persistence, adherence, and risk of exacerbation in patients with COPD treated with single-inhaler versus multiple-inhaler triple therapy: A prospective observational study in China.

Aim: This study sought to compare treatment persistence, adherence, and risk of exacerbation among patients with COPD treated with single-inhaler triple therapy (SITT) and multiple-inhaler triple therapy (MITT) in the Chinese population. Methods: This was a multicenter, prospective observational study. Patients with COPD from ten hospitals in Hunan and Guangxi provinces in China were recruited from 1 January 2020 to 31 November 2021 for the study and were followed up for oneyear. Treatment persistence, adherence, and exacerbation rates during the 12-month follow-up were analyzed in COPD patients treated with SITT and MITT. Results: A total of 1,328 patients were enrolled for final analysis, including 535 (40.3%) patients treated with SITT and 793 (59.7%) treated with MITT. Of these patients, the mean age was 64.9years and most patients were men. The mean CAT score was 15.2 ± 7.1, and the median (IQR) FEV1% was 54.4 (31.2). The SITT group had a higher mean CAT score, more patients with mMRC >1, and lower mean FEV1% and FEV1/FVC than the MITT patients. Moreover, the proportion of patients with ≥1 exacerbation in the previous year was higher in the SITT cohort. SITT patients had, compared to MITT patients, a higher proportion of adherence (proportion of days covered, PDC) ≥0.8 (86.5% vs. 79.8%; p = 0.006), higher treatment persistence [HR: 1.676 (1.356-2.071), p < 0.001], lower risk of moderate-to-severe exacerbation [HR: 0.729 (0.593-0.898), p = 0.003], and severe exacerbation [HR: 0.675 (0.515-0.875), p = 0.003], as well as reduced all-cause mortality risk [HR: 0.475 (0.237-0.952), p = 0.036] during the 12-month follow-up. Persistence was related to fewer future exacerbations and mortality than non-persistence in the SITT and MITT groups. Conclusion: Patients with COPD treated with SITT showed improved treatment persistence and adherence, as well as a reduction in the risk of moderate-to-severe exacerbation, severe exacerbation, and mortality compared to patients treated with MITT in the Chinese population. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR-POC-17010431.

Дисфункція дрібних дихальних шляхів та можливості її корекції при астмі

Abstract. Background. Although randomized controlled trials have shown that asthma control is an achievable goal, real-life studies over the past 20 years have shown that asthma remains poorly controlled in a significant proportion of patients, even among those receiving treatment at asthma specialist, and in patients with mild asthma who regularly take inhaled corticosteroids. Even when asthma control is achieved, it is not optimal on all GINA steps. The small airways have been recognized as the primary site of airflow limitation in asthma. The aim of the work: to study, according to the literature, the peculiarities of the dysfunction of the small airways in asthma and to evaluate the possibilities of its treatment. Materials and methods. Scientific articles that covered the pathophysiology of small airways disorders, their impact on asthma control, diagnostic methods, and pharmacological treatment methods were analyzed. The results. Airways with an internal diameter &lt; 2 mm, which do not contain cartilage in their walls and extend from the 8th generation of the airways to the periphery of the lung, are collectively called “small airways”. They are called the QUIET ZONE because they are difficult to assess and treat in patients with asthma who are not optimally controlled but have relatively normal FEV1 and disproportionate small airways dysfunction (SAD). Predominant in patients at all stages of treatment, associated with poor disease control. The ATLANTIS study showed that up to 91 % of patients with asthma have. The small airways have a high density of corticosteroid and β2-adrenoceptors, which means that they can be influenced. The main task is that the drugs should reach these small airways. Conventional inhalers that generate particles larger than 2 μm do not address the problem of SAD in patients with asthma. Inhaler devices that produce ultrafine particles of inhaled corticosteroids alone or in combination with long-acting β-agonists with a diameter of less than 2 μm have the potential to improve long-term asthma control along with a corresponding improvement in small airway function. The fixed combination of beclomethasone dipropionate with formoterol has optimal deposition in the respiratory tract — central pulmonary deposition accounts for 66 %, and peripheral — 34 % of the dose, thus the drug is delivered to both the central and peripheral respiratory tracts and affects inflammation and bronchoconstriction throughout the lungs. This is facilitated by MODULITE technology. The effectiveness and safety of the use of the BDP/F combination (Foster) in MART regimen is confirmed by a significant evidence base, which guaranteed its place in the Track1 treatment of asthma. Conclusions: Patients with asthma have a serious inflammatory process in the peripheral airways, which makes them the main site of obstruction in asthma; SAD predominates in patients at all stages of asthma, is associated with poor disease control, is responsible for air trapping, correlates with poor asthma control1, and predicts an increased risk of exacerbations in patients. The fixed combination of beclamethasone/formoterol in one inhaler (Foster) is the only extrafinely dispersed fixed combination of ICS/LABA that reaches the small airways; the fixed combination of BDP/Formoterol in the MART regimen provides a significant reduction in the frequency of severe complications, hospitalizations, emergency calls, and reduces the number of courses of systemic corticosteroids.

Clinically relevant effects of Mindfulness-Based Stress Reduction in individuals with asthma

BackgroundPsychological distress and comorbid psychopathology contribute to exacerbation risk in patients with asthma. Thus, interventions designed to reduce stress and improve emotion regulation, such as Mindfulness-Based Stress Reduction (MBSR), may augment standard care. Few studies have addressed this question and a paucity of data exists to determine the ability of MBSR to impact clinical outcomes in asthma. MethodsThis randomized controlled trial investigated effects of MBSR training on asthma control and airway inflammation, in relation to psychological symptoms, in adults with asthma. Participants were randomized to an 8-week MBSR training (n = 35) or wait-list control group (n = 34). Clinically relevant asthma assessments, including Asthma Control Questionnaire and inflammatory biomarkers, were collected at baseline and six approximately-monthly follow-ups. Self-reported mindfulness, distress, depression, and anxiety symptoms were assessed at baseline, post-intervention, and study completion. Chronic stress level was determined at baseline only. ResultsAsthma control improved significantly in individuals randomized to MBSR, relative to wait-list controls (p = .01; effect size d = 0.76), which was maintained at 4mo post-intervention. 32% of MBSR participants achieved a clinically significant improvement, based on the ACQ6 Minimally Important Difference, relative to 12% of wait-list participants. Moreover, MBSR-related improvement in asthma control was associated with a reduction in distress (p = .043) and the intervention was most efficacious for those with the highest baseline depressive symptoms (p = .023). Importantly, MBSR also reduced levels of exhaled nitric oxide, a biomarker of airway inflammation, relative to wait-list controls (p < .05). ConclusionSupporting and extending extant evidence of mind-body relationships in asthma and the benefits of stress reduction for these patients, this is, to the best of our knowledge, the first RCT to demonstrate that training in MBSR improves clinically relevant asthma outcomes. MBSR may thus be a valuable addition to optimal asthma management, particularly for those with comorbid psychopathology. Clinical trial registrationNCT02157766.

Lack of Association between Inhaled Corticosteroid Use and the Risk of Future Exacerbation in Patients with GOLD Group A Chronic Obstructive Pulmonary Disease.

Background: As most clinical trials have been performed in more symptomatic and higher-risk patients, evidence regarding treatment in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A chronic obstructive pulmonary disease (COPD) is limited. We assessed the distribution of inhaler treatment and sought to investigate the association between inhaled corticosteroid (ICS) use and future exacerbation in GOLD group A COPD patients. Methods: Patients with GOLD group A COPD who received maintenance inhalers were identified from a multicentre, prospective cohort in South Korea. Patients were categorized as group A when they had fewer symptoms and did not experience severe exacerbation in the previous year. Development of moderate or severe exacerbation during the 1-year follow-up was analysed according to baseline inhaler treatment. Results: In 286 patients with GOLD group A COPD, mono-bronchodilator (37.8%), dual-bronchodilator (29.0%), triple therapy (17.5%), and ICS/long-acting beta-2 agonist (15.4%) were used. Compared to patients without ICS-containing inhalers (N = 191), those using ICS (N = 95) were more dyspnoeic, and more likely to have asthma history, lower lung function, and bronchodilator response. During the 1-year follow-up, moderate or severe exacerbations occurred in 66 of 286 (23.1%) patients. In the multivariable logistic regression analysis, ICS-containing inhaler use was not associated with the development of exacerbation, even in the subgroup with a high probability of asthma–COPD overlap. Conclusion: Although about one-third of patients with GOLD group A COPD were using ICS-containing inhalers, use of ICS was not associated with a reduction in the future development of exacerbation.

Effect of timing of bronchodilator therapy initiation on exacerbations in patients with chronic obstructive pulmonary disease: a retrospective cohort study

BackgroundThe benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD.MethodsThis was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the “prompt therapy” group and the rest into the “delayed therapy” group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema.ResultsCompared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema.ConclusionsThis is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.

EFFECTIVENESS OF COPD MAINTENANCE THERAPY WITH LAMA/LABA VS LAMA/LABA/ICS IN A UNITED STATES CLAIMS DATABASE

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: This retrospective cohort study compared time to a) first hospitalization for community-acquired pneumonia and b) first COPD exacerbation in patients initiating maintenance therapy with the long-acting dual bronchodilator therapy tiotropium/olodaterol (T/O) vs triple therapy (TT) with long-acting muscarinic antagonist (LAMA)/long-acting beta agonist (LABA)/inhaled corticosteroids (ICS). METHODS: Administrative data from the US HealthCore Integrated Research Database (Jan 2013–Mar 2019) were used to compare patients for up to 1 year. Eligible patients were aged ≥40 years, diagnosed with COPD (not asthma), and had ≥1 inhaler prescription of fixed-dose T/O, or fixed or free TT (first prescription=index date). Propensity scores were calculated. Within the area of overlap, fine stratification and reweighting were used to balance measured covariates between the cohorts. Residual imbalances (standardized difference >0.10 [10%]) in the reweighted pseudo-population were adjusted for in the outcome models. A sensitivity analysis excluded patients with an exacerbation ≤30 days pre-index to minimize confounding e.g. due to higher TT prescription in frequent exacerbators. Further sensitivity analyses excluded patients with any prior use of maintenance therapy, and substituted the propensity score fine stratification/reweighting method with a 1:1 greedy match (propensity score caliper: 0.05). In all analyses, a Cox proportional hazard regression model was used to assess outcomes (as-treated analysis). RESULTS: The study population had 2,864 T/O and 24,326 TT users (after reweighting: 2,785 T/O and 15,465 TT users; mean age, 65.6 years; female, 47.1% [T/O] vs 49.7% [TT]). There were no differences in baseline characteristics, except for calendar year and season of cohort entry. No difference in prior exacerbations (any) was observed (std diff: <0.1); however, a higher proportion of TT users had severe exacerbations ≤1 year pre-index (32.7% vs 17.3%) and any exacerbations ≤30 days pre-index (25.8% vs 10.8%) vs T/O users. For T/O vs TT, adjusted hazard ratio (aHR) for exacerbation was 0.85 (95% CI: 0.76–0.96) (adjusted for calendar year, season of cohort entry). Excluding exacerbators ≤30 days pre-index balanced the cohorts (std diff: <0.1) in terms of prior exacerbations (any, moderate or severe). In this population, the aHR for exacerbation was 1.04 (95% CI: 0.91–1.19) (adjusted for calendar year, LABA/ICS use, season of cohort entry). Results were similar when applying 1:1 matching (aHR 1.02; 95% CI 0.84–1.24) and when restricting to treatment-naïve patients (no LABA, LAMA, ICS use prior to T/O or TT) (aHR 1.08; 95% CI 0.81–1.44). T/O users had a numerically lower risk of pneumonia than TT users (aHR 0.83; 95% CI 0.64–1.07). CONCLUSIONS: This study showed no benefit of TT vs T/O in reducing exacerbation risk in patients with no recent exacerbations, including treatment-naïve patients. In line with previous data, T/O was associated with a numerically lower risk of pneumonia vs TT. CLINICAL IMPLICATIONS: In an infrequently exacerbating population, prescribing T/O in place of TT appears not to increase exacerbation risk and could reduce pneumonia risk. DISCLOSURES: Employee relationship with Boehringer Ingelheim Please note: $20001 - $100000 by Alberto de la Hoz, source=Web Response, value=Salary Consultant relationship with HealthCore, Inc Please note: 2010-2018 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Consulting fee Employee relationship with Moderna Please note: Since Feb 2021 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Salary Owner/Founder relationship with Ciconia Inc Please note: 2018-2021 Added 05/04/2021 by Daina Esposito, source=Web Response, value=Ownership interest Employee relationship with Anthem Inc (HealthCore Inc) Please note: April 2019-present Added 05/04/2021 by Xintong He, source=Web Response, value=Salary Employee relationship with Boehringer-Ingelheim Please note: 2016- Added 05/03/2021 by Jukka Montonen, source=Web Response, value=Salary Advisory Committee Member relationship with GlaxoSmithKline Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria Advisory Committee Member relationship with Bayer Please note: Last 24 months Added 04/29/2021 by Jennifer Quint, source=Web Response, value=Honoraria

Patient characteristics, biomarkers and exacerbation risk in severe, uncontrolled asthma.

Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma. Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration. The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (F ENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL-1 and F ENO ≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and F ENO had greater prognostic value than either biomarker alone. Persistent eosinophil and F ENO elevations throughout the study period were associated with greater AAER. Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and F ENO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.

Serum hepatocyte growth factor as a predictor of disease severity and future exacerbations in patients with non-cystic fibrosis bronchiectasis

BackgroundSerum biomarkers associated with the severity of non-cystic fibrosis (CF) bronchiectasis are insufficient. This study determined the association of serum hepatocyte growth factor (HGF), osteopontin, and pentraxin-3 levels with disease severity and exacerbation in patients with non-CF bronchiectasis. MethodsSerum levels of HGF, osteopontin, and pentraxin-3 were measured in patients with clinically stable non-CF bronchiectasis (n = 61). The correlation between the biomarkers and bronchiectasis severity index (BSI) and FACED score was assessed using univariate and multivariate linear regression analyses. Predictive variables associated with exacerbation were analyzed using a Cox proportional hazards model and the time to first exacerbation in high and low HGF groups during the observation period was compared using Kaplan-Meier survival curves. ResultsThe BSI showed significant correlation with HGF (r = 0.423; p = 0.001) and pentraxin-3 (r = 0.316; p = 0.013). The FACED score was significantly correlated with HGF (r = 0.406; p = 0.001). Univariate and multivariate linear regression analysis revealed that serum level of HGF was independently associated with both scoring systems. The high HGF group showed a significantly shorter time to first exacerbation (Log-rank test, p = 0.014). Multivariate Cox proportional hazards regression analysis revealed that high serum HGF level and colonization with non-pseudomonas organisms were independent predictors of future exacerbations (HR 2.364; p = 0.024 and HR 2.438; p = 0.020, respectively). ConclusionSerum level of HGF is a potential biomarker that is closely associated with disease severity and future risk of exacerbations in patients with non-CF bronchiectasis.

Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma

Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.

A Clinical Model for the Prediction of Acute Exacerbation Risk in Patients with Idiopathic Pulmonary Fibrosis.

Objective To develop and validate a risk assessment model for the prediction of the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) in patients with idiopathic pulmonary fibrosis (IPF). Methods We enrolled a total of 110 patients with IPF, hospitalized or treated as outpatients at Xuzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from July 2012 to July 2020. Of these, 78 and 32 patients were randomly assigned to training and test groups, respectively. The risk factors for AE-IPF were analyzed using logistic regression analysis, and a nomographic model was constructed. The accuracy, degree of calibration, and clinical usefulness of the model were assessed with the consistency index (C-index), calibration diagram, and decision curve analysis (DCA). Finally, the stability of the model was tested using internal validation. Results The results of logistic regression analysis showed that a history of occupational exposure, diabetes mellitus (DM), essential hypertension (EH), and diffusion capacity for carbon monoxide (DLCO)% predicted were independent risk factors for AE-IPF prediction. The nomographic model was constructed based on these independent risk factors, and the C-index was 0.80. The C-index for the internal validation was 0.75, suggesting that the model had good accuracy. The decision curve indicated that for a threshold value of 0.04–0.66, greater clinical benefit was obtained with the AE-IPF risk prediction model. Conclusion A customized AE-IPF prediction model based on a history of occupational exposure, DM, EH, and DLCO% predicted provided a reference for the clinical prediction of AE-IPF.

Effect of Inhaled Corticosteroid Withdrawal on Chronic Obstructive Pulmonary Disease Exacerbations in Patients Taking Triple Therapy at Baseline.

PurposeIn the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk. However, many patients were not taking triple therapy before study participation. This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.Patients and MethodsThe effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis. Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.ResultsOverall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening. Baseline characteristics were generally similar between groups. Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89–1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94–1.19]). However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81–1.41] (≥100 cells/μL) to 1.45 [0.58–3.60] (≥400 cells/μL).ConclusionConsistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening. Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.

Identification of exacerbation risk in patients with liver dysfunction using machine learning algorithms.

The prediction of the liver failure (LF) and its proper diagnosis would lead to a reduction in the complications of the disease and prevents the progress of the disease. To improve the treatment of LF patients and reduce the cost of treatment, we build a machine learning model to forecast whether a patient would deteriorate after admission to the hospital. First, a total of 348 LF patients were included from May 2011 to March 2018 retrospectively in this study. Then, 15 key clinical indicators are selected as the input of the machine learning algorithm. Finally, machine learning and the Model for End-Stage Liver Disease (MELD) are used to forecast the LF deterioration. The area under the receiver operating characteristic (AUC) of MELD, GLMs, CART, SVM and NNET with 10 fold-cross validation was 0.670, 0.554, 0.794, 0.853 and 0.912 respectively. Additionally, the accuracy of MELD, GLMs, CART, SVM and NNET was 0.669, 0.456, 0.794, 0.853 and 0.912. The predictive performance of the developed machine model execept the GLMs exceeds the classic MELD model. The machine learning method could support the physicians to trigger the initiation of timely treatment for the LD patients.

Stability and Predictors of Poor 6-min Walking Test Performance over 2 Years in Patients with COPD.

Poor performance in the 6-min walk test (6MWT < 350 m) is an important prognostic indicator of mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Little is known about the stability of this state over time and what factors might predict a poor 6MWT performance. To determine the stability of 6MWT performance over a 2-year period in COPD patients participating in annual medical follow-up visits, and to assess the ability of several clinical, pulmonary, and non-pulmonary factors to predict poor 6MWT performance, we prospectively included 137 patients with stable COPD (mean age, 66.9 ± 8.3 years). The 6MWT was scored at baseline and 2-year follow-up. To evaluate clinical, pulmonary, and non-pulmonary variables as potential predictors of poor 6MWT performance, we used multiple logistic regression models adjusted for age, sex, weight, height, and 6MWT performance at baseline. Poor 6MWT performance was stable over 2 years for 67.4% of patients. Predictors of poor 6MWT performance included a five-repetition sit-to-stand test score ≤2 (OR, 3.01; 95% CI, 1.22–7.42), the percentage of mobility activities with limitations (OR, 1.03; 95% CI, 1.00–1.07), and poor 6MWT performance at baseline (OR, 4.64; 95% CI, 1.88–11.43). Poor 6MWT performance status was stable for the majority of COPD patients. Lower scores on the five-repetition sit-to-stand test and a higher number of mobility activities with limitations were relevant predictors of poor 6MWT performance over 2 years. Prognostic models based on these non-pulmonary factors can provide non-inferior discriminative ability in comparison with prognostic models based on only pulmonary factors.