Marjan Kerkhof

This study suggests caution when prescribing systemic corticosteroids to patients with #COVID19 who show mild-to-moderate pulmonary symptoms because a harmful effect cannot be excludedhttps://bit.ly/3P4nOjQ

Purpose: This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations. Patients and Methods: A historical cohort study was conducted using data from the UK’s Optimum Patient Care Research Database. Patients with COPD ≥ 40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥ 2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥ 2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated. Results: A total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV₁ < 80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94– 1.09]), acute respiratory events (IRR = 0.98 [0.92– 1.04]), acute OCS courses (IRR = 1.01 [0.91– 1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90– 1.09]), but not for mMRC (OR = 0.93 [0.69– 1.27]) or risk of pneumonia (HR = 0.50 [0.14– 1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness. Conclusion: This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.

Introduction: Early identification of preventable risk factors of COPD progression is important. Whether exacerbations have a negative impact on disease progression is largely unknown. We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD. Methods: Patients diagnosed with mild/moderate COPD (obstruction and FEV₁% predicted 50– 90%), aged ≥ 35 years, and a smoking history, who had ≥ 6 years of UK electronic medical records after initiation of maintenance therapy were studied. Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥ 1 exacerbation over a 6-year period and FEV₁ decline, adjusted for sex, age, anthropometrics and smoking habits. Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization. Results: Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥ 1 exacerbation. The mean annual FEV₁ decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥ 1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥ 1 exacerbation every year. Patients with more years with ≥ 1 exacerbation had a lower mean FEV₁ at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations. When counting years with ≥ 2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥ 2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV₁ at diagnosis). Conclusion: Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.

Purpose: Prior work suggests a threshold of four courses/year of systemic corticosteroid (SCS) therapy is associated with adverse consequences. The objective of this study was to investigate the onset of adverse outcomes beginning at SCS initiation in a broad asthma population. Patients and methods: This historical matched cohort study utilized anonymized, longitudinal medical record data (1984–2017) of patients (≥18 years) with active asthma. Matched patients with first SCS prescription (SCS arm) and no SCS exposure (non-SCS arm) were followed until first outcome event. Associations between time-varying exposure measures and onset of 17 SCS-associated adverse outcomes were estimated using Cox proportional hazard regression, adjusting for confounders, in separate models. Results: We matched 24,117 pairs of patients with median record availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4 and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in the non-SCS arm, patients prescribed SCS had significantly increased risk of osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI 1.87–5.19), pneumonia (2.68; 2.30–3.11), cardio-/cerebrovascular diseases (1.53; 1.36–1.72), cataract (1.50; 1.31–1.73), sleep apnea (1.40; 1.04–1.86), renal impairment (1.36; 1.26–1.47), depression/anxiety (1.31; 1.21–1.41), type 2 diabetes (1.26; 1.15–1.37), and weight gain (1.14; 1.10–1.18). A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0– Conclusion: Our findings suggest urgent need for reappraisal of when patients need specialist care and consideration of nonsteroid therapy.

Purpose We investigated the use of asthma medication by children and the association of use as recommended by guidelines with modifiable risk factors: parental attitudes, knowledge of asthma medication and information provided by health care providers. Methods Questionnaire data were obtained from parents of 229 8-year-old children participating in the prevention and incidence of asthma and mite allergy birth cohort who used asthma medication in the past 12 months. They reported on their child's medication use, their own knowledge and attitudes towards the medication and their satisfaction with the information they received from health care providers. Results Irregular use of inhaled corticosteroids (ICS) was common: 40% of the parents only gave their child ICS when the child felt breathless and 52% only ‘when the child needed it’; 15% of the parents tried to avoid giving medication, and about 25% of the parents sometimes discontinued medication. Parental knowledge of how asthma medication should be given was a major determinant of guideline-recommended use: Of the parents who knew that anti-inflammatory drugs should be taken everyday (53% of all parents), 84% reported that they actually gave their child the medicines everyday as compared with 25% of the parents who did not know this. Guideline-recommended use was also significantly associated with parental satisfaction with the amount of information received from health care providers. These associations were independent of maternal school education. Conclusions Our findings suggest that substantial improvements in the use of asthma medication are feasible, and this could considerably improve the effectiveness of current asthma treatment. Copyright © 2014 John Wiley & Sons, Ltd.

Objective. Most epidemiological, questionnaire-based studies collect data on body weight and height but not on waist circumference (WC), although WC is suggested to be clinically more relevant. It is unknown whether valid WC data of school-aged children can be obtained by questionnaires. In this study the agreement between parental reported and measured WC in 8-year-old children was investigated and compared with the agreement between parental reported and measured body mass index (BMI). Methods. Data on body weight, height, and WC of 1 292 8-year-old Dutch children were collected by a medical examination and a questionnaire. Mean differences, correlations and misclassification based on parental reported values were calculated. Results. Mean differences between parental reported and measured values were small. Pearson correlation coefficient for measured and reported WC was 0.83 compared with 0.90 for measured and reported BMI. Parents of children with a high BMI tended to underreport their child's WC and body weight. A total of 22.7% of overweight children were misclassified as being normal weight based on reported WC compared with measured WC. For BMI this applied to 23.7% of children. Conclusion. Parental reported waist circumference corresponded well with measured values, indicating that reported waist circumference can be used to study associations between waist circumference and risk factors or health outcomes.

Background: A higher prevalence of respiratory symptoms and an associated increase in health care utilization among children with parents who smoke is to be expected. From previous studies however, it appears that parents who smoke may underutilize health services for their children, especially with respect to respiratory care. This study explores the validity and generalizability of the previous assumption. Methods: Data were obtained from a Dutch birth-cohort study; the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) project. Information regarding parental smoking, the child's respiratory symptoms and health care use and potential confounders were obtained by postal questionnaires. Multivariate logistic models were used to relate parental smoking to the child's respiratory symptoms and health care use. Results: The study comprised 3,564, 4-year old children. In the crude analysis, respiratory symptoms were more frequent among children with a parent who smoked, while health care utilization for respiratory symptoms was not significantly different between children with or without a parent who smoked. In the multivariate analyses, maternal smoking had a larger impact on the child's respiratory symptoms and health care use as compared to paternal smoking. Maternal smoking was positively associated with mild respiratory symptoms of the child, adjusted odds ratio [AOR] 1.50 (1.19–1.91), but not with severe respiratory symptoms AOR 1.03 (0.75–1.40). Among children with mild respiratory symptoms, children with a mother who smoked were less likely to be taken to the general practitioner (GP) for respiratory symptoms, than children with mothers who did not smoke, AOR 0.58 (0.33–1.01). This finding was less pronounced among children with severe respiratory symptoms AOR 0.86 (0.49–1.52). Neither GP visits for non-respiratory symptoms nor specialized care for respiratory disease were significantly associated with parental smoking. Conclusion: Mothers who smoke appear to underutilize health care for their children with mild respiratory symptoms. Health care workers should be informed about this phenomenon. Inquiring after the respiratory health of the children during regular visits to healthy baby clinics may help to track potential underutilization of care.