In this study the investigators aim to investigate the extent to which in patients with chronic obstructive pulmonary disease narrowing of the vocal cords causes a positive pressure within the airways thus improving airflow and lung function. This information will be captured in the upright and lying down positions and an estimate of the magnitude of the effect will be formed by offsetting the pressure by asking the patients to breathe using a commercially available device used to treat sleep apnoea called a CPAP machine. This is an observational study in which the observation of laryngeal aperture, and mouth and oesophageal pressure at differing levels of applied CPAP will be recorded for analysis in patients with COPD and in normal subjects without COPD. All will have the same measurements, observations, and interventions to allow us to observe and measure pressure, laryngeal aperture, and airflow .

In patients with chronic obstructive pulmonary disease (COPD) flow limitation inherent to the condition causes gas trapping and consequently over-inflation of the lung termed hyperinflation which worsens on exercise. Expiratory airflow can be maximized if the intrinsic positive pressure in the lung (Positive end expired pressure,PEEP) is offset by externally applied pressure (Expiratory positive airway pressure,EPAP) and it has been noted that patients with COPD do this by pursed lips breathing on expiration. The applicants have shown in a preliminary study that patients with COPD also close their vocal cords during expiration and is hypothesised that the function of the glottic narrowing was to provide an external positive expiratory pressure thus reducing flow limitation.

Relatively few data exist on laryngeal airflow in humans. One therapy that is increasingly used in the treatment of acute and chronic respiratory failure is non invasive pressure ventilation. Devices used for this oscillate between a high Inspiratory positive airway pressure (IPAP) and a lower Expiratory positive airway pressure (EPAP) but there remains uncertainty as how best to titrate the EPAP. We speculate that the optimum EPAP would be one to most reduce glottic narrowing on the basis that this would optimise expiratory flow and reduce the drive to glottic narrowing. The aim of this study is to test this hypothesis and to identify the range of external applied EPAP which minimises glottic narrowing in COPD patients in the erect and supine positions.

Technical advances with the use of continuous laryngoscopic examination (CLE) now provide a feasible and safe method to directly observe laryngeal movement from a fixed position. We aim to measure intra-thoracic pressure using an oesophageal balloon during respiration and to relate this to the CLE movement of the larynx.

At the same time we will be measuring airflow and volume with a pneumotachograph. This will allow us to identify the effect of glottic narrowing on intra-thoracic pressure and to see if the glottic narrowing does lead to an increased positive end expired pressure in the chest ( positive end expired pressure intrathoracic,PEEPi) and the extent to which it can be offset using EPAP delivered by a positive pressure machine (continuous positive airways pressure,CPAP).

The design of this study is a one visit physiological study which is an observational study with no blinding of investigator or participants.

We intend to study 10 controls with normal lung function and no history of COPD and 20 patients with COPD. They will attend for a single 3 hour period which will start with full explanation of the procedures to be undertaken and informed consent will be obtained on all aspects of the investigation by one of the investigators who is fully trained to obtain consent in research projects.

The subjects will be examined and have lung function tests if they have not already been carried out in the previous 6 weeks

The subject will be seated in an armchair and after application of local anaesthetic to the nose will be assisted to swallow an oesophageal balloon catheter in a deflated state inserted via a nostril and assisted by sipping water whilst the balloon is swallowed. The position of the balloon will be identified by measuring the length swallowed and positioned to the lower third of the oesophagus. A small quantity of air will be introduced into the balloon (1.0ml) to inflate the balloon and the tubing connected to a pressure measuring device situated next to the chair.

Next the subject will have introduced into their other nostril a fibre-optic laryngoscope which will be passed under direct vision to the back of the throat where the larynx in movement can be seen The output from the laryngoscope will be recorded digitally.

The subject will place over their mouth and nose a modified facemask through which they will be able to breathe without difficulty modified to admit the measurement catheters above. Attached to the mask will be a pneumotachograph which measures airflow and tubing to allow the pressure at the mouth to be varied.

This will allow the movement of the larynx on quiet breathing at rest to be observed with intra-thoracic pressure measured at the same time and the airflow at the mouth recorded simultaneously.

Once the subject is comfortable with these devices and relaxed in the chair recording of the laryngeal movement , pressures and airflow will be commenced and continue for 5 minutes. At the end of this time the subject will be asked to make an inspiratory capacity manoeuvre (breathe in as far as they can).

Subsequently the mouth pressure will be varied by 1cm H2O(1cm H20 = pressure produced by a column of water of 1cm depth) increments in random order 0-15cm H2O with 5 minutes at each level.

The protocol will then be repeated with the subject lying flat after which the catheter and the laryngoscope will be withdrawn.

Data will be stored securely in accordance with the Royal Brompton Hospital information governance and security protocols and access to personal data will only be by members of the research team. We will seek permission from the participants to inform their general practitioner or any other health professionals.

All data will be handled in accordance with the United Kingdom(UK) data protection Act 1998 and the condition of the main Research Ethics Committee (REC) approval.

The UK National Health Service Indemnity Scheme will meet any potential liability of the sponsors to harm to participants arising from the management of the research. any adverse events will be recorded in the case notes and a case report form and any serious adverse events will be reported to the study sponsor and the research ethics committee.

Inclusion Criteria:

• patients with COPD
• Gold stage 11 as severity of disease
• aged 40+
• male and female
• at least 1 pack/day of cigarettes for >10 years
• normal subjects
• no evidence of Chronic Obstructive pulmonary disease (COPD) on spirometry
• < 1 pack of cigarettes/day for 10 years
• age >40
• male and female

Exclusion Criteria:

• an inability to comprehend what is proposed or travel to appointments
• restrictive lung pathology as assessed by history and lung function testing
• active infection
• evidence of cardiac disease
• inability to tolerate any of the following
• the fibre-optic laryngoscope
• the passing and retention of the oesophageal balloon
• the wearing of a face mask
• the application of a low level of positive pressure to the face mask and mouth ( CPAP, EPAP)
• those who are receiving a trial drug as part of another study at the time of study
• pregnancy

20 patients with chronic obstructive pulmonary disease (COPD) Gold stage 11 as severity of disease aged 40+ male and female at least 1 pack/day of cigarettes for >10 years

10 normal subjects no evidence of Chronic obstructive pulmonary disease (COPD) on spirometry < 1 pack of cigarettes /day for 10 years age >40 male and female