The effect of twice daily aclidinium bromide/formoterol fumarate 340/12 mcg vs. once daily tiotropium 'respimat' 5mcg on static and dynamic hyperinflation in patients with COPD during 24 hours.

Exertional dyspnea is the most important symptom of COPD patients. Exertional
dyspnea is multifactorial, but derangement of ventilator mechanics due to lung
hyperinflation (LH) is thought to play an important role. Static LH causes an
upward shift in the pressure-volume curve, where there is increased elastic
loading, due to loss of elastic properties of the lung without loss of the
elastic properties of the chest wall. Together with increasing intrathoracic
gas volume, the residual volume also increases, due to premature closure of the
small airways, a feature otherwise known as gas or air trapping. Static LH is
highly predictive for dynamic LH, a situation where the end-expiratory lung
volume increases during exercise due to reduced lung elastance and insufficient
time to deflate the lungs. Dynamic LH is importantly related to exertional
dyspnea and exercise limitation and is the major contributing factor of
physical inactivity in COPD, regardless of their BODE or GOLD classification.
Bronchodilation therapy is the cornerstone of the treatment of patients with
COPD as it reduces dyspnea, increases exercise capacity, and improves quality
of life in individuals with COPD. Randomized controlled trials have been
evaluated consistently by spirometric outcomes, mostly forced expiratory volume
in the first second. Also, the pharmacological effects of different products on
lung hyperinflation outcomes were increasingly studied in recent years.
However, there is no information on the 24 hour effect of pharmacotherapy on
static lung hyperinflation and a twice daily compared to once daily regimen has
not been studied. In addition dual to single bronchodilator therapy has only
been scarcely studied and results were contradictory.
It has been established that COPD symptoms vary throughout the day, but there
is a scarcity of information of long-acting bronchodilation on 24 hour symptoms
in COPD patients. Also, sleep quality is known to be poor in COPD patients,
with increased nocturnal symptoms. Recently, it was shown that tiotropium is
associated with decreased COPD-related night-time awakenings. Night-time
awakenings were associated with increased nocturnal rescue medication use.
Also, a significant improvement of overall night-time and early-morning symptom
severety and limitation of early-morning activities were observed with
aclidinium bromide/formoterol fumarate 340/12 µg and both monotherapies.

Therefore we aimed to study the 24 hour effect of twice daily
aclidinium/formeterol versus once daily tiotropium on serial static and dynamic
lung hyperinflation measurements, as well as (24 hour) symptoms and sleep
quality.
Tiotropium was chosen as a comparator because it has developed as the gold
standard for long acting bronchodilator therapy for research.

Experimental, randomized, 2-arm, cross-over study.

Aclidinium bromide/formoterol fumarate (Duaklir Genuair), 1 dose of 340/12mcg
per 12 hours via DPI. Tiotropium (Spiriva Respimat), 2 doses of 2,5 mcg once
per 24 hours via PMDI.

This exploratory study will be performed using two kinds of medications which
are already registered for treatment of COPD. Therefore, the risks are minimal
and predictive.