Acute Effect of Pulmonary Desufflation on Cardiac Performance in COPD Patients
Acute Effect of Pulmonary Desufflation on Cardiac Performance in COPD Patients
Chronic Obstructive Pulmonary disease (COPD) is one of the major clinical entities that
 causes thousands of deaths every year all over the world and weights a lot on the health care
 system of every country in terms of direct and indirect costs. The physiopathological
 modifications that characterise COPD are represented by irreversible (sometimes partially
 reversible) airflow obstruction, and bronchiolar inflammation. Lungs that develop emphysema
 lack of elastic recoil and imply increased resistances and airflow obstruction due to loss of
 lung parenchyma and supporting elastic structures. All these modifications produce air
 trapping and so lung hyperinflation. The latter is precisely the cause of the symptoms and
 particularly dyspnoea which is often heavily perceived by COPD patients and that drives to
 the limitation of daily activities. Lung hyperinflation and the other alterations that occur
 in COPD imply gas retention and increase in pulmonary vascular resistances. Considering that
 the rib cage has limited elastic properties, the effects of gas trapping and lung parenchymal
 damage on mediastinum and particularly on heart mechanics is indisputable. Together with
 alveolar hypoxia, lung hyperinflation is responsible for the development, as the disease
 progresses, of the cor pulmonale. Tha latter causes pulmonary hypertension and increased
 mechanic load during right heart chambers contraction and relaxation. Those alterations may
 effect left heart chambers too.

 Airflow obstruction in COPD is usually treated by inhaled bronchodilators and
 corticosteroids. The main and most used bronchodilators are represented by beta 2 agonists
 (short, long and ultra-long acting) and anticholinergic inhalatory drugs, which can be also
 short, long and ultra long acting. Among ultra long acting beta 2 agonists, indacaterol is
 characterised by quick onset of action (5 minutes), and guarantees an effective
 bronchodilation duration of 24 hours. It is also known that it has an important effect on
 reducing lung hyperinflation decreasing residual volume and consequently allowing an increase
 of inspiratory capacity. The purpose of our study is to evaluate the effects of indacaterol
 on lung hyperinflation in COPD subjects of any stage and with lung air trapping, and the
 consequent potential effects on heart performance evaluated by cardiac trans thoracic echo
 color doppler.
In a paper recently published, Barr et al, supposed that pulmonary emphysema and bronchial
 obstruction were inversely related with ventricular telediastolic volume, with the ejection
 volume and the ejection fraction in patients with severe pulmonary disease. The mechanisms
 that are involved in the development of cor pulmonale are the increase of pulmonary vascular
 resistances, lung hyperinflation and hypoxic vascular constriction. All the mentioned
 contribute to the generation of right cardiac failure and consequently, left cardiac failure.
 The authors assessed lung hyperinflation by CT scan, pulmonary function by spirometry, and
 cardiac kinetic and mechanics by magnetic resonance. They concluded that the amount of
 emphysema and bronchial obstruction were related with a worse telediastolic left ventricular
 volume and stroke volume, no relation was found with ejection fraction. It was evident that
 patients with severe pulmonary disease and with no present cardiac diseases, had sub-clinic
 modifications that one day may lead them to the development of cor pulmonale.

 The effect of bronchodilation, with its effect on lung hyperinflation, may have a role in
 producing some modifications in this context. That's why that the aim of our study is
 centered on the evaluation of the effect of bronchodilation firstly on diastolic right
 ventricular function and also on interventricular septum motility, on the ejection fraction
 and on the kinetics of right cardiac chambers assessed by cardiac echocardiography
Inclusion Criteria:

 -  Signature of informed consent

 -  COPD patients with age raging from 50 to 85 years old

 -  Patients with at least a history of COPD of one year

 -  COPD patients clinically stable in the last three months

 -  COPD subjects with FEV1 (Forced Expiratory Volume at one second)<70% of predicted
 value

 -  FEV1/FVC (Forced Vital Capacity)<88% (males) or <89% (females) of LLN (Lower Levels of
 Normality)

 -  COPD former or active smokers with at least a smoking history of 20 pack years

 -  Residual Volume (RV) >= 125% predicted value

 -  No Cardiac ultrasound signs of Cor Pulmonale

 Exclusion Criteria:

 -  Acute Bronchial Exacerbation at recruitment

 -  Fertile women with age between 18 and 50 years old or with active period

 -  Pregnancy

 -  Subjects enrolled in other clinical trials or that have taken part in one of them in
 the month preceding the enrollment.

 -  FEV1/FVC more than 70% of predicted value in basal conditions

 -  FEV1 more than 70% of predicted value in basal conditions

 -  Residual Volume < 125% predicted value

 -  Known deficit of alpha 1 antitrypsin

 -  Subjects that underwent a Lung Volume Reduction Surgery (LVRS)

 -  Subjects with known positivity to Human Immunodeficiency Virus (HIV)

 -  Misuse of alcool or drugs

 -  Lack of compliance in performing respiratory tests

 -  Subjects not capable to follow the study prescriptions because of psychic disorders or
 language problems.

 -  Long Term Oxygen Therapy with flows > 6 litres per minute (l/min) at rest

 -  Cor Pulmonale

 -  Patients that cannot take Indacaterol for cardiologic reasons