Advanced Chronic Obstructive Pulmonary Disease (COPD) is a condition with a negative prognosis that causes symptoms such as wheezing and fatigue that dramatically reduce the quality of life of the person with the disease.

Typically, the advanced stage of COPD is characterized by a fluctuating pattern and recurrent hospitalizations, and by a vicious circle in which dyspnoea increases and exercise tolerance reduces, causing depression with social isolation, low quality of life and increased risk of death.

Muscle dysfunction in these patients contributes together with dynamic hyperinflation to increased fatigue and dyspnoea during exercise, leading to early interruption of exertion, before reaching the maximal aerobic capacity.

The European and American guidelines of the American Thoracic Society / European Respiratory Society relating to the patient with COPD emphasize the need for the patient to undergo Respiratory Rehabilitation (RR) programs. The RR should include training programs as they improve exercise capacity, dyspnoea and quality of life more than programs that do not include training.

To our knowledge, no study has been performed in COPD with chronic respiratory failure (CRF) patients to evaluate the effects of High Interval Training compared to continuous submaximal training. Moreover, no different interval training protocols have been compared. However, studies conducted on healthy subjects or on other pathologies, show how the interval training protocol induces, in a specific and diversified way, physiological modifications to the cardio-respiratory and muscular systems.

In COPD patients with respiratory failure with marked muscular dysfunction and associated systemic changes (systemic inflammation, vascular changes, pulmonary hypertension, right heart failure, etc.), the evaluation of the best training program would reinforce the rehabilitative indications not yet fully proposed in the Guidelines. Moreover, the evaluation of the response to different training stimuli could provide important information on the reversibility of the intolerance to the effort in this patient population.

Primary aim of this study will be to evaluate the physiological effects on exercise tolerance of three training modalities performed in an intra-hospital setting (classic endurance training compared to two high-intensity interval programs - Long Interval Training and Short Interval training) in a population of COPD patients with chronic hypoxemic respiratory failure.

Advanced (Chronic Obstructive Pulmonary Disease) COPD is a condition with a negative prognosis that causes symptoms such as wheezing and fatigue that dramatically reduce the quality of life of the person with the disease.

Typically, the advanced stage of COPD is characterized by a fluctuating pattern and recurrent hospitalizations, and by a vicious circle in which dyspnoea increases and exercise tolerance reduces, which in turn causes depression and associated social isolation, low quality of life and increased risk of death.

Muscle dysfunction in these patients contributes together with dynamic hyperinflation to increased fatigue and dyspnoea during exercise, leading to early interruption of exertion, before reaching maximum aerobic capacity.

The European and American guidelines of the American Thoracic Society / European Respiratory Society relating to the patient with Chronic Obstructive Pulmonary Disease (COPD) emphasize the need for the patient to undergo Respiratory Rehabilitation (RR) programs. The RR should include training programs as they improve exercise capacity, dyspnoea and quality of life more than programs that do not include training.

However, although there are many studies referring to the benefits of physical exercise in patients with COPD with mild-to-moderate severity, the recent guidelines provide few recommendations for types of training and its efficacy for patients with advanced disease that have already developed Chronic Respiratory Failure (CRF) and use of Long Term Oxygen Therapy (LTOT).

Thanks to a retrospective study on 1047 patients, the Authors have previously shown that patients with COPD with CRF respond to a rehabilitation program (in terms of exercise tolerance, blood gases, dyspnoea and quality of life) as well as COPD patients without CRF.

A recent meta-analysis conducted by Paneroni et al. supports the effectiveness of exercise in improving quality of life and functional capacity in patients with severe COPD (FEV1 <35%), with or without CRF. The study showed that so far the training proposed to these patients is mainly of moderate-intensity endurance and performed primarily through the continuous use of exercise bikes or free walking. In a similar way to patients with moderate or mild severity, the setting of the exercise was mainly proposed using a speed or a load that approximates around 70% of the maximum value reached in an incremental test.

Regarding the type of exercise to be used in patients with COPD, several recent papers suggest the opportunity to use interval training even in high intensity. The purpose of the High Interval Training is to repeatedly stress the cardio-respiratory and muscular system, above "what is normally required for normal activities, through" bouts of high intensity and short duration exercise".

In subjects with COPD, this type of training could guarantee a delay in the development of the dynamic hyperinflation mechanism typical of the pathology and could guarantee greater physiological modifications regarding the classical submaximal continuous training. Despite some physiological studies that have tested this effect, the results of the clinical application of these interventions appear - in subjects with moderate COPD - similar to that got with continuing training. However, the protocols proposed to date appear to be diversified in terms of approach, especially concerning the intensity and duration of the active and passive phases.

To our knowledge, no study has been performed in COPD with CRF patients to evaluate the effects of High Interval Training compared to continuous submaximal training and no protocols on different interval training have been compared. Indeed, studies conducted on healthy subjects or on other pathologies, show how the interval training protocol induces, in a specific and diversified way, physiological modifications to the cardiorespiratory and muscular systems.

In patients with respiratory failure with marked muscular dysfunction and associated systemic changes (systemic inflammation, vascular changes, pulmonary hypertension, right heart failure, etc.), the evaluation of the best training program would reinforce the rehabilitative indications not yet fully proposed in the Guidelines. Moreover, the evaluation of the response to different training stimuli could provide important information on the reversibility of the intolerance to the effort in this patient population.

Inclusion Criteria:

• age> 50 years
• clinical definition of COPD according to GOLD guidelines (10) with FEV1 / FVC G 70% and FEV1 <50% of the above
• PaO2 in air-ambient lower than 60 mmHg evaluated through arterial blood gas analysis
• oxygen therapy prescription for more than 18 hours/ day for at least one month
• clinical stable condition

Exclusion Criteria:

• presence of pulmonary diseases other than COPD
• respiratory tract infections in the last 4 weeks
• termination