Measuring burden of disease in both asthma and COPD by merging the ACQ and CCQ: less is more?

Symptoms of asthma and COPD often overlap, and both diseases can co-exist in one patient. The asthma control questionnaire (ACQ) and clinical COPD questionnaire (CCQ) were developed to assess disease burden in respectively asthma or COPD. This study explores the possibility of creating a new questionnaire to assess disease burden in all obstructive lung diseases by integrating and reducing questions of the ACQ and CCQ. Data of patients with asthma, COPD and asthma-COPD overlap (ACO) were collected from a primary and secondary care center. Patients completed ACQ and CCQ on the same day. Linear regression tested correlations. Principal Component Analysis (PCA) was used for item reduction. The secondary cohort with asthma and COPD patients was used for initial question selection (development cohort). These results were reproduced in the primary care cohort and secondary cohort of patients with ACO. The development cohort comprised 252 patients with asthma and 96 with COPD. Correlation between ACQ and CCQ in asthma was R = 0.82, and in COPD R = 0.83. PCA determined a selection of 9 questions. Reproduction in primary care data (asthma n = 1110, COPD n = 1041, ACO = 355) and secondary care data of ACO patients (n = 53) resulted in similar correlations and PCA-derived selection of questions. In conclusion, PCA determined a selection of nine questions of the ACQ and CCQ: working title 'the Obstructive Lung Disease Questionnaire'. These results suggest that this pragmatic set of questions might be sufficient to assess disease burden in obstructive lung disease in both primary as secondary care.

Aberrant characteristics of peripheral blood innate lymphoid cells in COPD, independent of smoking history.

Background: Distinguishing asthma and COPD can pose challenges in clinical practice. Increased group 1 innate lymphoid cells (ILC1s) have been found in the lungs and peripheral blood of COPD patients, while asthma is associated with elevated levels of ILC2s. However, it is unclear whether the inflammatory characteristics of ILC1s and ILC2s differ between COPD and asthma. This study aims to compare peripheral blood ILC subsets and their expression of inflammatory markers in COPD patients, asthma patients and controls. Methods: The study utilised multi-colour flow cytometry to analyse peripheral blood ILC populations in clinically stable COPD patients (n=38), asthma patients (n=37), and smoking (n=19) and non-smoking (n=16) controls. Results: Proportions of peripheral blood inflammatory CD4+ ILC1s were significantly higher in COPD patients than in asthma. Proportions of CD4- ILC1s were increased in COPD patients compared to asthma patients and smoking controls. Frequencies of CD117- ILC2s were significantly reduced in COPD patients compared with asthma patients. In contrast, the fraction of inflammatory CD45RO+ cells within the CD117- ILC2 population was significantly increased. Principal component analyses showed that combined features of the circulating ILC compartment separated COPD patients from asthma patients and both control groups. Conclusion: Our in-depth characterisation of ILC1 and ILC2 populations in peripheral blood revealed significant differences in their phenotypes between COPD and asthma patients and smoking or non-smoking controls. These findings suggest a role for both ILC subsets in COPD disease pathology, independent of smoking history, and may have implications for patient stratification and therapy development.

Efficacy and safety of dupilumab as add-on therapy for patients with severe asthma: A real-world Dutch cohort study.

BACKGROUND: Dupilumab as add-on treatment for severe uncontrolled asthma (SA) has shown to be effective and safe by phase-III-trials. Real-world data on clinical efficacy and safety is limited. OBJECTIVE: We aim to investigate the efficacy and safety of dupilumab as add-on therapy for SA in a real-world cohort. MATERIAL AND METHODS: The primary endpoint was annually exacerbation-rate (AER). Secondary outcomes were maintenance oral corticosteroid (mOCS) dependency, asthma control (ACQ-5), pulmonary function (FEV1), quality of life (AQLQ) and frequency of reported adverse events (AEs). RESULTS: Overall, 148 patients were included. Median AER [IQR] reduced from 4.00 [2.00-5.00] at baseline to 1.00 [0.00-2.00] at 12 months (p < 0.001). mOCS-dependency reduced from 39.9% of the patients at baseline, to 20.3% at 6 months and to 14.9% at 12 months (p < 0.001). Median ACQ improved from 3.00 [2.00-3.80] at baseline to 1.80 [0.60-2.95] after 6 months and to 1.40 [0.20-2.60] after 12 months (p < 0.001). Median FEV1 (L) improved from 2.21 [1.58-2.85] to 2.50 [2.00-3.06] at 6 months and to 2.51 [1.88-3.04] after 12 months (p < 0.001). The outcomes improved most in subgroups with high eosinophils (≥300/µL) or FeNO (≥50 ppb) at baseline. AEs were reported by 45.3% (67/148), of which headache was most frequent. CONCLUSIONS: This study indicates that dupilumab as add-on therapy for SA is associated with significant improvements in exacerbation-rate, mOCS-dependency, asthma control, pulmonary function, and quality of life. These results are in line with those of previous phase-III-trials.

Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters.

BACKGROUND: The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV1, symptoms and impairment of the health status of patients with chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included. METHODS: The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531-9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering. RESULTS: Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel's clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL. CONCLUSIONS: We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.

Adult but not childhood onset asthma is associated with the metabolic syndrome, independent from body mass index.

INTRODUCTION: Adult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA. STUDY DESIGN AND METHODS: This cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria. RESULTS: Eighty-one participants were included (27 AoA, 25 CoA, 29 controls). AoA was associated with the metabolic syndrome (Odds Ratio = 3.64 95% CI (1.16-11.42) p = 0.03, Nagelkerke R2 = 0.26), adjusted for age, sex, body mass index and smoking habits. AoA patients had higher median serum IL-6 and leptin-adiponectin (LA) ratio compared to controls (IL-6 (pg/mL): 3.10 [1.11-4.30] vs. 1.13 [0.72-1.58], p = 0.002 and LA ratio (pg/mL): 6.21 [2.45-14.11] vs. 2.24 [0.67-4.71], p = 0.0390). This was not observed in CoA and controls. CONCLUSION: AoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Bacterial lysate add-on therapy to reduce exacerbations in severe asthma: A double-blind placebo-controlled trial.

BACKGROUND: Asthma exacerbations are frequently induced by respiratory tract infections (RTIs). Bacterial lysates have been described to possess immune-modulatory effects and reduce RTIs as well as asthma symptoms in children. However, whether bacterial lysates have similar effects in adult asthma patients is unknown. AIMS: To reduce asthma exacerbations by add-on bacterial lysate therapy in adults with severe asthma and to characterize the clinical and immune-modulatory effects of this treatment. METHODS: Asthma patients (GINA 4) with ≥2 annual exacerbations in the previous year were included. The intervention regimen consisted of OM-85/placebo for 10 consecutive days per month for 6 months during two winter seasons. Primary end-point was the number of severe asthma exacerbations within 18 months. The study was approved by the national and local ethical review board and registered in the Dutch Trial Registry (NL5752). All participants provided written informed consent. RESULTS: Seventy-five participants were included (38 OM-85; 37 placebo). Exacerbation frequencies were not different between the groups after 18 months (incidence rate ratio 1.07, 95%CI [0.68-1.69], p = 0.77). With the use of OM-85, FEV1% increased by 3.81% (p = 0.04) compared with placebo. Nasopharyngeal swabs taken during RTIs detected a virus less frequently in patients using OM-85 compared to placebo (30.5% vs. 48.0%, p = 0.02). In subjects with type 2 inflammation adherent to the protocol (22 OM-85; 20 placebo), a non-statistically significant decrease in exacerbations in the OM-85 group was observed (IRR = 0.71, 95%CI [0.39-1.26], p = 0.25). Immune-modulatory effects included an increase in several plasma cytokines in the OM-85 group, especially IL-10 and interferons. Peripheral blood T- and B cell subtyping, including regulatory T cells, did not show differences between the groups. CONCLUSION: Although OM-85 may have immune-modulatory effects, it did not reduce asthma exacerbations in this heterogeneous severe adult asthma group. Post hoc analysis showed a potential clinical benefit in patients with type 2 inflammation.

Association between elevated serum triglycerides and asthma in patients with obesity: An explorative study.

Background: Adults with a high body mass index (BMI) have an increased risk of developing asthma. To explore the impact of increased lipids on the presence of asthma, this study investigated the relationship between lipid levels and inflammatory markers in patients with asthma and controls with obesity. Objective: We hypothesized that higher lipid levels are more prevalent in patients with obesity and asthma. Methods: In this explorative cohort study, 96 patients with asthma and 45 controls were included. All the patients participated in one of three asthma studies; two of these studies included only patients with obesity. An asthma diagnosis was defined by the presence of typical clinical symptoms, reversible airway obstruction (+12% improvement in forced expiratory volume in the first second of expiration after bronchodilator), or bronchial hyperreactivity (Histamine PC20 < 8 mg/mL), or a fractional exhaled nitric oxide of > 50 ppb. We compared lipid levels and neutrophils and eosinophils in patients with asthma and the controls with a wide BMI range (17.8-63.8 kg/m²). Multivariable logistic regression was used to analyze the data. Results: Serum triglycerides were statistically significantly higher in patients with obesity and asthma adjusted for BMI, blood eosinophils, and statin use (odds ratio [OR] 2.56 [95% confidence interval, 1.34-4.88]; p = 0.004). Inclusion or exclusion of those who used long-acting ß2-agonists and inhaled corticosteroids led to comparable adjusted ORs for blood triglyceride and blood eosinophils levels. Conclusion: Elevated serum triglycerides were associated with the presence of asthma in patients with obesity. This indicated that elevated triglycerides might be a yet unrecognized trait that contributed to the development of asthma. The precise cause and effect of these high triglyceride levels in the patients with asthma and with obesity were not determined in this study.Clinical trial Trial registration NCT03278561, www.clinicaltrials.gov; NL4262, NL3056, trialregister.nl.

The impact of the involvement of a healthcare professional on the usage of an eHealth platform: a retrospective observational COPD study.

BACKGROUND: Ehealth platforms, since the outbreak of COVID-19 more important than ever, can support self-management in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this observational study is to explore the impact of healthcare professional involvement on the adherence of patients to an eHealth platform. We evaluated the usage of an eHealth platform by patients who used the platform individually compared with patients in a blended setting, where healthcare professionals were involved. METHODS: In this observational cohort study, log data from September 2011 until January 2018 were extracted from the eHealth platform Curavista. Patients with COPD who completed at least one Clinical COPD Questionnaire (CCQ) were included for analyses (n = 299). In 57% (n = 171) of the patients, the eHealth platform was used in a blended setting, either in hospital (n = 128) or primary care (n = 29). To compare usage of the platform between patients who used the platform independently or with a healthcare professional, we applied propensity score matching and performed adjusted Poisson regression analysis on CCQ-submission rate. RESULTS: Using the eHealth platform in a blended setting was associated with a 3.25 higher CCQ-submission rate compared to patients using the eHealth platform independently. Within the blended setting, the CCQ-submission rate was 1.83 higher in the hospital care group than in the primary care group. CONCLUSION: It is shown that COPD patients used the platform more frequently in a blended care setting compared to patients who used the eHealth platform independently, adjusted for age, sex and disease burden. Blended care seems essential for adherence to eHealth programs in COPD, which in turn may improve self-management.

Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19.

BACKGROUND: Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19. METHODS: A prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity-assessed by an increased waist-hip ratio-and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses. RESULTS: In total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014). CONCLUSION: This study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference. TRIAL REGISTRATION NUMBER: NL8580.