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Pathological Conditions, Anatomical

Hereditary Hemorrhagic Telangiectasia

Pulmonary Arteriovenous Malformation

A group of up to 30 healthy controls will be recruited to have a cardiopulmonary exercise test and a blood test.

A group of up to 30 pulmonary AVM patients will be recruited to have a cardiopulmonary exercise test, and a blood test.

Most patients with pulmonary AVMs have underlying hereditary hemorrhagic telangiectasia (HHT). If there is a difference between pulmonary AVM and control groups that does not correct following embolization of pulmonary AVMs, a group of up to 30 people with HHT but no evidence of pulmonary AVMs will be selected to have a cardiopulmonary exercise test and a blood test.

On Day 1, subjects will have the test in the Exercise Suite of Hammersmith Hospital, London, UK. They will have painless skin probes placed on their fingers, chest, and legs to monitor heart rate, ECG, blood oxygen levels, and oxygen delivery during the test. Subjects will also be shown how to breathe through a mouthpiece with a nose clip on, and how to indicate on a sliding device whether they feel breathless. They will then start cycling against a very low resistance at a steady speed. As long as they feel comfortable, there will be a gradual increase in work load until they feel they cannot keep going at the same speed. They can also stop sooner for any reason. Afterwards, while they are "cooling down" (within the hour on Day 1), they will fill in a short questionnaire describing how they feel.

Cardiopulmonary exercise test

On same day (Day 1), the subject will have 20-30mls of blood (that is, 4-6 teaspoonful) taken for analysis.

Blood test

Claire L Shovlin

Pulmonary arteriovenous malformations (PAVMs) are a rare vascular condition affecting the lungs. PAVMs lead to low blood oxygen levels, yet are very well tolerated by patients. This study will examine the exercise capacity of PAVM patients using formal cardiopulmonary exercise tests performed on a stationary bicycle.

It is well known that the lung is the site at which oxygen enters the blood stream, diffusing from the alveolar air sacs into the pulmonary capillaries. This newly oxygenated blood is carried to the heart in the pulmonary veins, then passes into the systemic circulation to provide oxygen to the tissues.

Patients with pulmonary arteriovenous malformations (PAVMs) have abnormal vascular connections between pulmonary arteries and pulmonary veins in the lung. Blood flowing through PAVMs therefore bypasses the oxygenation sites in the pulmonary capillaries. Low blood oxygen levels (hypoxemia) is frequent in PAVM patients but breathlessness (dyspnea) is not. The investigators have shown that dyspnea was not a common presenting complaint in a large UK series, and that there is little correlation between severity of dyspnea in PAVM patients, and blood oxygen levels.

In this study the investigators will address the question "Why are hypoxemic PAVM patients not more dyspneic?"

The investigators will address this by first performing standardised cardiopulmonary exercise testing, as used in the clinic, on age and sex matched patients with PAVMs and healthy controls. Physiological parameters will be compared, to test the null hypothesis that the impact of exercise on PAVM patients' cardiopulmonary systems does not differ to normal controls.

If the expected differences are confirmed, the investigators will examine if there is any difference to normals by re-examining the exercise tolerance of the PAVM cohort after they have had their PAVMs treated by embolization.

Most patients with PAVMs have an underlying hereditary vascular disorder, hereditary haemorrhagic telangiectasia. Assuming the expected differences between PAVM patients and controls are confirmed, the investigators will therefore also examine which pattern HHT patients without PAVMs display. Finally, cellular and molecular methods will be used to dissect mechanistic pathways.

Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs

Hypoxemia, Dyspnea, and Exercise Tolerance in Patients With Pulmonary Arteriovenous Malformations

Of the many measurements and derived indices that can be measured during cardiopulmonary exercise testing, the peak consumption of oxygen (VO2 max) is perhaps the best indicator of integrated cardiorespiratory capacity. The principle research question will therefore test the null hypothesis that "The VO2 max does not differ between PAVM patients and age matched healthy controls."

We will also test in univariate and multiple regression analyses whether breathing reserve differs between PAVM patients and controls.

We will also test in univariate and multiple regression analyses whether ventilatory efficiency differs between PAVM patients and controls.

Imperial College London

Immune System Diseases

Asthma

30 patients with pulmonary AVMs and no airflow obstruction will undergo cardiopulmonary exercise testing

30 patients with pulmonary AVMs and airflow obstruction will undergo cardiopulmonary exercise testing

Subjects will have the test in the Exercise Suite of Hammersmith Hospital, London, UK. They will have painless skin probes placed on their fingers, chest, and legs to monitor heart rate, ECG, blood oxygen levels, and oxygen delivery during the test. Subjects will also be shown how to breathe through a mouthpiece with a nose clip on, and how to indicate on a sliding device whether they feel breathless. They will then start cycling against a very low resistance at a steady speed. As long as they feel comfortable, there will be a gradual increase in work load until they feel they cannot keep going at the same speed. They can also stop sooner for any reason. Afterwards, while they are "cooling down", they will fill in a short questionnaire describing how they feel. 20-30mls of blood will be taken for analysis.

Claire L Shovlin, PhD FRCP

Luke Howard, DPhil FRCP

Pulmonary arteriovenous malformations (PAVMs) are a rare vascular condition affecting the lungs. PAVMs lead to low blood oxygen levels, yet are very well tolerated by patients. This study will examine the exercise capacity of PAVM patients using formal cardiopulmonary exercise tests performed on a stationary bicycle, and whether this is affected by the presence of concurrent airflow obstruction, such as due to asthma.

It is well known that the lung is the site at which oxygen enters the blood stream, diffusing from the alveolar air sacs into the pulmonary capillaries. This newly oxygenated blood is carried to the heart in the pulmonary veins, then passes into the systemic circulation to provide oxygen to the tissues.

Patients with pulmonary arteriovenous malformations (PAVMs) have abnormal vascular connections between pulmonary arteries and pulmonary veins in the lung. Blood flowing through PAVMs therefore bypasses the oxygenation sites in the pulmonary capillaries. Low blood oxygen levels (hypoxemia) is frequent in PAVM patients but breathlessness (dyspnea) is not. The investigators have shown that dyspnea was not a common presenting complaint in a large UK series, and that there is little correlation between severity of dyspnea in PAVM patients, and blood oxygen levels.

In this study the investigators will address the question "Do PAVM patients have lower exercise tolerance if they have concurrent airflow obstruction?" The primary outcome measure will be the total body oxygen consumption in mls/min/kg, at peak exercise (the V\[dot\]O2 peak (also known as "VO2 max")).

The investigators will address this by first performing standardised cardiopulmonary exercise testing, as used in the clinic and our previous study (11/H0803/9), on age and sex matched patients with PAVMs. 30 will be recruited with airflow obstruction, and 30 without airflow obstruction. Physiological parameters will be compared, to test the null hypothesis that the impact of exercise on PAVM patients' cardiopulmonary systems does not differ according to the presence or absence of airflow obstruction. Cellular and molecular methods will be used to dissect mechanistic pathways.

Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs With and Without Airflow Obstruction

Hypoxemia, Dyspnea, and Exercise Tolerance in Patients With Pulmonary Arteriovenous Malformations , With and Without Airflow Obstruction

Of the many measurements and derived indices that can be measured during cardiopulmonary exercise testing, the peak consumption of oxygen (VO2 max) is perhaps the best indicator of integrated cardiorespiratory capacity. The principle research question will therefore test the null hypothesis that "The VO2 max does not differ between PAVM patients with and without airflow obstruction."

We will also test in univariate and multiple regression analyses whether breathing reserve differs between PAVM patients with and without airflow obstruction.

We will also test in univariate and multiple regression analyses whether ventilatory efficiency differs between PAVM patients with and without airflow obstruction.

Pulmonary arteriovenous malformations (PAVMs) are thin-walled abnormal vessels which provide direct capillary-free communications between the pulmonary and systemic circulations. Patients with PAVMs have usually have low blood oxygen levels and are at risk of other complications including strokes, brain abscesses, pregnancy-related complications and haemorrhage. We hypothesise that the complications of PAVM patients arise from their PAVMs and not the more recognised intracardiac forms of shunting. We propose to perform echocardiograms to enable assessment of the presence of other causes of capillary-free communications between the pulmonary and systemic circulations.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs	NCT02436213	Pulmonary Arter... Hereditary Hemo...	Cardiopulmonary... Blood test	18 Years -	Imperial College London
Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs With and Without Airflow Obstruction	NCT02458703	Pulmonary Arter... Hereditary Hemo... Asthma COPD	Cardiopulmonary...	16 Years - 80 Years	Imperial College London
Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs	NCT02436213	Pulmonary Arter... Hereditary Hemo...	Cardiopulmonary... Blood test	18 Years -	Imperial College London
Contrast Echocardiography in Patients With Pulmonary Arteriovenous Malformations (PAVMs)	NCT00733759	Pulmonary Arter...		-	Imperial College London
Cardiopulmonary Exercise Testing to Evaluate Pulmonary AVMs With and Without Airflow Obstruction	NCT02458703	Pulmonary Arter... Hereditary Hemo... Asthma COPD	Cardiopulmonary...	16 Years - 80 Years	Imperial College London

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