High Density Lipoproteins and Type 2 Inflammatory Biomarkers are Negatively Correlated in Atopic Asthmatics

Juan Carlos Ivancevich Wednesday, 19 July 2017 11:28

Amisha V. Barochia1 , Elizabeth M. Gordon1 , Maryann Kaler1 , Rosemarie A. Cuento1 , Patricia Theard1 , Debbie M. Figueroa1 , Xianglan Yao1 , Nargues A. Weir1 , Maureen L. Sampson2 , Mario Stylianou3 , David F. Choy4 , Cecile T.J. Holweg4 , Alan T. Remaley5 , and Stewart J. Levine1


Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL (high-density lipoprotein) and apolipoprotein A-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics, and 163 non-asthmatic subjects with and without atopy. Serum lipids and lipoproteins were quantified using standard laboratory assays and nuclear magnetic resonance (NMR) spectroscopy. Absolute blood eosinophils were quantified by complete blood counts. Periostin levels were measured using the Elecsys Periostin assay. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL-cholesterol and total HDL particles measured by NMR spectroscopy (HDLNMR). Serum periostin levels negatively correlated with total HDLNMR. In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.

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Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study

Juan Carlos Ivancevich Monday, 17 July 2017 16:43

The Lancet Child & Adolescent Health

In Press, Corrected Proof

Clare MurrayMDabPhilip FodenMScaLesley LowePhDaHannah DurringtonPhDaProf Adnan CustovicMDcProf Angela SimpsonMDa



Concerns have been expressed about asthma overdiagnosis. The UK National Institute of Health and Care Excellence (NICE) proposed a new diagnostic algorithm applying four lung function measures sequentially (ratio of forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] <70%, bronchodilator reversibility ≥12%, fractional exhaled nitric oxide [FeNO] ≥35 parts per billion, and peak expiratory flow variability >20%). We aimed to assess the diagnostic value of three of the tests individually, and then test the proposed algorithm in symptomatic children.


We used follow-up data at age 13–16 years from the Manchester Asthma and Allergy Study, a prospective, population-based, birth cohort study. We initially present results for the whole population, then by subgroup of disease. To simulate the situation in primary care, we included participants reporting symptoms of wheeze, cough, or breathlessness in the previous 12 months and who were not on regular inhaled corticosteroids. We used an epidemiological definition of current asthma, defined as all three of physician-diagnosed asthma, current wheeze, and current use of asthma treatment, reported by parents in a validated questionnaire. We assigned children with negative answers to all three questions as non-asthmatic controls. We also measured spirometry, bronchodilator reversibility, and FeNO at follow-up; data for peak expiratory flow variability were not available. We calculated the proportion of participants with a current positive lung function test at each step of the algorithm, and recorded the number of participants that met our definition of asthma.


Of 1184 children born into the cohort, 772 attended follow-up at age 13–16 years between July 22, 2011, and Nov 11, 2014. Among 630 children who completed spirometry, FEV1:FVC was less than 70% in ten (2%) children, of whom only two (20%) had current asthma. Bronchodilator reversibility was positive in 54 (9%) of 624 children, of whom only 12 (22%) had current asthma. FeNO was 35 or more parts per billion in 115 (24%) of 485 children, of whom 29 (25%) had current asthma. Only four of 56 children with current asthma had positive results for all three tests (spirometry, bronchodilator reversibility, and FeNO). Conversely, 24 (43%) of the 56 children with current asthma were negative on all three tests. FEV1:fvc (p=0·0075) and FeNO (p<0·0001), but not bronchodilator reversibility (p=0·97), were independently associated with asthma in multivariable logistic regression models. Among children who reported recent symptoms, the diagnostic accuracy of the algorithm was poor.


Our findings challenge the proposed cutoff values for spirometry, the order in which the lung function tests are done, and the position of bronchodilator reversibility within the algorithm sequence. Until better evidence is available, the proposed NICE algorithm on asthma diagnosis should not be implemented in children.

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Prevalence and characteristics of asthma–COPD overlap syndrome identified by a stepwise approach

Juan Carlos Ivancevich Saturday, 01 July 2017 15:35
Hiromasa Inoue,1 Takahide Nagase,2 Satoshi Morita,3 Atsushi Yoshida,4 Tatsunori Jinnai,4 Masakazu Ichinose5
1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 3Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 4Medical Department, AstraZeneca K.K., Osaka, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

Background and objective: There is increasing recognition of asthma–COPD overlap syndrome (ACOS), which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood. The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).
Methods: This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD. Clinical data, including spirometry results, were retrieved from medical records. For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire.
Results: Of the 1,008 patients analyzed, 167 (16.6%) had syndromic features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2%) also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1), respectively, and therefore were identified as having ACOS. Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability), and 328 patients (32.5%, ≥12%/≥400 mL FEV1 clinical variability) had both the features. Patients identified as having ACOS were of significantly younger age, had a shorter duration of COPD, lower number of pack-years, better lung function, milder dyspnea symptoms, and higher peripheral blood eosinophil values compared with patients with COPD alone. The rate of exacerbations in the previous year was not significantly different between the ACOS and COPD groups.
 Using a stepwise approach, as stated in the GINA/GOLD report, the proportions of patients identified as having ACOS were found to be 9.2% and 4.2% (depending on the FEV1variability cutoff used) among the 1,008 outpatients medically treated for COPD in a real-life clinical setting.

Keywords: obstructive lung diseases, airway hyperresponsiveness, respiratory function tests, differential diagnosis

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Patient preferences for dry powder inhaler attributes in asthma and chronic obstructive pulmonary disease in France: a discrete choice experiment

Juan Carlos Ivancevich Friday, 07 July 2017 20:22
Natalia HawkenSaku TorvinenMohamed Elmoctar NeineIkbel AmriMondher ToumiSamuel AballéaAdam Plich and Nicolas Roche



Dry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies. Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients’ preferences for different attributes of DPIs.


Attributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study). An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase). A fractional factorial design including three blocks of 12 choice sets was created. Each choice set comprised three alternatives: two fictitious inhalers and the patient’s current inhaler. Marginal utilities were estimated using a ranked ordered logit model. Interactions between attributes and disease (asthma or COPD) were tested.


Six DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties. Overall, 201 patients with asthma and 93 with COPD were included in the online survey. Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77–€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95–€6.02]). Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65–€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98–€ 7.77]).


This study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.

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Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016 – results from three population surveys

Juan Carlos Ivancevich Tuesday, 27 June 2017 14:30



During the latter half of the 20th century the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends after 2010, especially regarding studies separating allergic asthma from non-allergic asthma is lacking.


The aim was to estimate prevalence trends of current asthma, both allergic and non-allergic, from 1996 to 2016.


Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis was used as a marker for allergic sensitization in order to define allergic asthma.


The prevalence of current asthma increased from 8.4% (95%CI 7.8-9.0) in 1996 to 9.9% (95%CI 9.2-10.6) in 2006 and 10.9% (95%CI 10.1-11.7) in 2016 (p=<0.001). Allergic asthma increased from 5.0% (95%CI 4.5-5.5) in 1996 to 6.0% (95%CI 5.4-6.6) in 2006 and further to 7.3% (95%CI 6.6-8.0) in 2016 (p<0.001), while the prevalence of non-allergic asthma remained stable around 3.4-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use, and allergic rhino-conjunctivitis also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.

Conclusions & Clinical Relevance

The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

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Editor: Juan C. Ivancevich, MD

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