Mesa 3- Actualización en el tratamiento sintomático de la EPOC Congreso A.R.C en EPOC. Madrid Oct. 2016

1. Hospital Universitario Virgen
Macarena. Sevilla
Dr. Agustín Valido

2. [ERS] A home-centered disease management
program in severe chronic obstructive
pulmonary disease (Results of the COPD patient
Management European Trial-COMET)
Kessler R, Casan P, Koehler D, Tognella S, Viejo JL, dal Negro R, et al.
Mesa 3

3. Introduction.-
Severe COPD impacts deeply on daily activities an is asociated
with high hospitalisation rate and prognosis.
Objetive.-
To investigate the effectiveness of home-centered disease
management program in reducing all-cause hospitalisations in
severe COPD.

4. Methods.-
- GOLD III/IV COPD patiens with at least 1 exacerbation in the
previous year were randomised to disease (DM) or usual (UM)
management.
- DM intervention included self-management coaching (“Livin
Well With COPD”) and decision support in case of clinical
worsening over about 1 year.

5. Results.- (I)
- 319 patients (74.3% on HOT, 27.3% on HMV) entered follow-up
(Intention-To-Treat, ITT).
- Difference in yearly number of unscheduled all-cause hospital
days (primary outcome) was -5,32 days [95%CI -13,69; 3,05](DM
17.4±35.4, UM 22.6±41.8, p=0.161, Wilcoxon, ITT).
- It was -7.99 days [95%CI -16.62; 0.64], p=0.070) in Per Protocol
(PP, eligibility criteria not fulfilled and/or having received <25%
of planned coaching, n=288).

6. Results.- (II)
- When considering acute care hospital days (without nursing
facility days), adjusted means difference was -6.90 days ([95%CI
-14.49; 0.68], p=0.074) in ITT and -8.26 ([95%CI -16.39; -0.12],
p=0.047) in PP.
- No between-group differences were found in health status
(SGRQ total score).
- More patients died in UM (n=23) than in DM (n=3, p<0.001, Chi2
),
mainly from respiratory cause (16 patients).

7. Conclusions.-
- This 1-yr intervention in severe COPD showed a non-
statistically significant reduction of all-cause hospital days
(those including nursing facility).
- Significant reductions in acute care hospital days (PP) and a
lower number of deaths were shown with DM.

8. [ERS] Pharmacological characterization of the
mechanism of action leading to synergism
between glycopyrronium bromide and
indacaterol fumarate
Calzetta L, Rogliani P, Puxeddu E, Ora J, Facciolo F, Matera MG, et al.
Mesa 3

9. Introduction.-
Nowadays there is a considerable gap in knowledge concerning the
mechanism(s) by which long-acting β2 agonists (LABAs) and long-acting
muscarinic antagonists (LAMAs) interact to induce bronchodilation.
Objetive.-
This study aimed to identify the mechanism(s) causing the synergistic
interaction between the LAMA glycopyrronium bromide (GLY) and the LABA
indacaterol fumarate (IND) in human bronchial tissue.

10. Methods.-
- The influence of GLY plus IND was assessed on the release of
acetylcholine (ACh) and concentrations of cAMP in human
isolated airways.
- Iberiotoxin (IbTX, 100 nM) was used to block the KCa++
channels,
tetanus toxin (TeTX, 10 nM) to inhibit the synaptic vesicle
exocytosis of ACh, and quinine (100 μM) to reduce the release of
non-neurogenic ACh.

11. Results.- (I)
- The co-administration of GLY and IND reduced the release of ACh
from epithelial cells (-36.6±4.7%, P<0.01 vs. control) but not from
bronchi, and enhanced cAMP levels in both bronchi
(+479.4±62.4%, P<0.01 vs. control) and epithelial cells
(+29.1±7.1, P<0.05 vs. control), an effect that was inhibited by
IbTX.

12. Results.- (II)
- TeTX inhibited the release of parasympathetic ACh (−60.0%
±1.2%, P<0.001 vs. control), and both GLY and IND further
enhanced this effect (−68.4%±1.8%, P<0.001 vs. control).
- Quinine did not influence (P>0.05) the effectiveness of
GLY/IND combination in reducing the non-neurogenic release
of ACh.

13. Conclusions.-
- GLY/IND co-administration leads to a synergistic improvement
of bronchodilation by increasing cAMP concentrations in both
airway smooth muscle and bronchial epithelium and by
decreasing ACh release from the epithelium.

14. [ATS] Improvement in lung function with
indacaterol/glycopyrrolate (ind/gly) in
patientswith moderate to severe COPD from the
Us: a subgroup alalysis from the Flight1 and
Flight2 studies
Kerwin E, Mahler DA, FowlerTaylor A, Maitra S, Banerji D
Mesa 3

15. Introduction.-
IND/GLY 27,5/15,6 μg demostrated superior improvement in lung
funtion along with rapid onset versus its monocomponents
(IND27,5 μg and GLY 15,6 μg) and placebo in patients with
moderate-to-severe COPD. Here we present the lung function data
in the subgroup of patients from the US.

16. Methods.-
- FLIGHT1 and FLIGHT2 were replicate, 12 week, multi-center.
Randomized, double-blind studies that evaluated the safety and
efficacy of IND/GLY.
- Lung funtion was evaluated in terms of the area under the curve up
to 12 h for forced expiratory volumen in 1 second (FEV1 AUC0-12H),
TROUGH FEV1and peak FEV1 during 4 hours post dose with IND/GLY
versus its monocomponents and placebo.
- Onset of action was evaluated by measuring the improvement in
FEV1 at 5 min post-morning dose on Day1.

17. Results.- (I)
- Of 2038 patients from the overall pool, 1104 were fron the US an
included in this analysis (IND/GLY, n=274; IND, n=256; GLY,
n=292; placebo, n=278).
- IND/GLY showed superior improvement in lung function with a
statistically significant (p>0,001) improvement in FEV1AUC0-12H at
week 12, compared with placebo, IND and GLY (Table 1).

18. Results.- (II)
- Improvements in trough FEV1 and peak
FEV1 were also statistically significant with
IND/GLY versus placebo, and its
monocompnents at Week 12 (all
p<0,001).
- In addition, IND/GLY showed rapid onset
of action as indicated by a statistically
significant improvement in FEV1 at 5 min
post-dose on Day 1 versus placebo
(p<0,001).

19. Conclusions.-
- In this post-hoc analysis, IND/GLY b.i.d. Demonstrated superior
improvement in lung fuction with a rapid onset of action
compared with monocponents and placebo.