Abstracts from CIPP XVI Meeting Libon june 2017.pdf

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#A53 − Once-daily Tiotropium Respimat Add-on Therapy

FEV1 response versus pboR (Table). The safety and tolerability of

Improves Lung Function in Patients Aged 6–17 Years with

tioR in both trials were comparable with those of placebo.

Severe Symptomatic Asthma.







Hamelmann E , Vogelberg C , Goldstein S , El Azzi G , Engel M ,
Sigmund R 5, Szefler S 6

Children’s Center, Evangelisches Krankenhaus Bielefeld, and Allergy Center
of the Ruhr University − Bochum, Germany; 2 Department of Pulmonology
and Allergy, University Hospital Carl Gustav Carus, Technical University of
Dresden − Dresden, Germany; 3 Island Medical Research, Rockville Center −
New York, USA; 4 TA Respiratory Diseases, Boehringer Ingelheim Pharma
GmbH & Co. KG − Ingelheim am Rhein, Germany; 5 Global Biometrics and
Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG − Biberach
an der Riss, Germany; 6Department of Pediatrics, Children’s Hospital of
Colorado and the University of Colorado School of Medicine − Aurora,

Tiotropium Respimat add-on therapy is an effective bronchodilator,
producing clinically meaningful improvements versus placebo in lung
function in patients aged 6–17 years with severe symptomatic asthma,
mirroring findings in adult patients with symptomatic asthma.

#A55 − HMGB1 as a Biomarker of Inhaled Corticosteroid
Treatment Response in Moderate-Severe Asthmatic
Children: A Single Center Pilot Study.
Brafa Musicoro V 1, Leonardi S 1, Manti S 2, Salpietro C 2,
Cuppari C 2, Tardino LG 1, Parisi GF 1

Tiotropium Respimat (tioR) add-on therapy to inhaled corticosteroids
(ICS) with or without additional controllers has been shown to improve
lung function in Phase II and III studies of adults, adolescents and children

Department of Clinical and Experimental Medicine, University of Catania −
Catania, Italy; 2Department of Pediatrics, Unit of Pediatric Genetics and
Immunology, Università of Messina − Messina, Italy

with symptomatic asthma. We present a pooled analysis of lung function
data in adolescents and children with severe symptomatic asthma.

High mobility group box 1 (HMGB1) is a new molecule involved in


pro-inflammatory responses, abnormally expressed in serum and






parallel-group, 12-week trials in patients aged 6–11 years (VivaTinA-asthma; NCT01634152) and 12–17 years (PensieTinA-asthma;

sputum of allergic asthmatic patients [1, 2]. The aim of this study was
to investigate the role of HMGB1 as guidance for treatment
management of asthmatic children.

NCT01277523) with severe symptomatic asthma. Patients received
once-daily tioR 5 μg (two doses of 2.5 μg), tioR 2.5 μg (two doses of

Materials and Methods

1.25 μg) or placebo Respimat (pboR) as add-on to high-dose ICS plus

30 asthmatic patients and 44 healthy children were enrolled. The

another controller or as add-on to medium-dose ICS plus two other

patients were classified according to GINA disease severity criteria

controllers. ICS dose was as defined in the Global Initiative for Asthma

(mild, moderate and severe). Sputum HMGB1 Levels and lung function

2009 (PensieTinA) and 2010 (VivaTinA) guidelines. Patients were

indices (FEV1%; FEF 25–75%) were recorded in the cohort study at

required to have a ≥3-month (PensieTinA) or ≥6-month (VivaTinA)

baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled

history of asthma and be symptomatic at screening and before

corticosteroids (ICS) treatment (Table 1).

randomization by Asthma Control Questionnaire (interviewer-admin-


istered; VivaTinA) mean score of ≥1.5. The primary end point of both
studies was change from baseline (response) in peak forced expiratory
volume in 1 second within 3 hours post-dose (FEV1[0–3h]); the key
secondary end point was trough FEV1 response (measured 10 minutes
before the next dose of study medication); a further end point was
forced expiratory flow between 25% and 75% of the forced vital
capacity (FVC; FEF[25–75%]) response; the post hoc end point was
trough FEV1/FVC ratio. All end points were measured at Week 12.
793 participants (VivaTinA n = 401; PensieTinA n = 392) were
randomized across both trials; 792 were included in this pooled full
analysis set. Baseline demographics and disease characteristics were
balanced between treatment groups. TioR add-on therapy improved
lung function in the pooled population at Week 12, with tioR 5 μg

Sputum HMGB1 Levels were significantly higher in all patients with
asthma (p < 0.0001). An inverse correlation between sputum HMGB1
Levels and pulmonary function parameters was observed only in
moderate (T0: FEV1% r:-0.9891, p < 0.001; T3: FEV1% r:-0.6763,
p < 0.001; T6: FEV1% r:-0.5419, p < 0.05) and in severe asthmatic
children (T0: FEV1% r:-0.8696, p < 0.001; T3: FEV1% r:-0.6477,
p < 0.05; T6: FEV1% r:-0.8627, p < 0.001) (Fig. 1). After ICS treatment,
a significant decrease of sputum HMGB1 Levels was noted in
moderate (T0: 93.44 ± 20.65 ng/ml vs. T3: 77.96 ± 1.81 ng/ml vs.
T6: 67.75 ± 3.01 ng/ml; p < 0.0001) and in severe asthmatic children

130.3 ± 7.48 ng/ml



156.9 ± 1.09 ng/ml



116.08 ± 4.77 ng/ml; p < 0.0001). The area under the ROC curve,
performed in order to define the diagnostic profile of sputum HMGB1
Levels in identifying asthmatic children, was 0.713.

showing superior and significant improvements in peak FEV1(0-3h)


response, trough FEV1 response, FEF(25–75%) response and FEV1/

In addition to the findings that HMGB1 is a sensitive biomarker of

FVC ratio versus pboR, and tioR 2.5 μg showing superior improve-

allergic asthma in children, our data firstly demonstrate a significant

ments in peak FEV1(0-3h) response, FEF(25–75%) response and

correlation between the decrease in HMGB1 Levels and a successful

FEV1/FVC ratio versus pboR, with numerical improvements in trough

treatment response.