1. History
In 1891, the disease was first described by the German physician Ernst von Romberg in his studies for pathological anatomy.
In the decade from 60 to 70, the fashion of taking drugs for anorexia carries the disease in the foreground to the attention of the public.
In 1973, the World Health Organization in Geneva organized the First International Conference of Pulmonary Hypertension, which is the first diagnostic classification.
In 1982, a group with leader Professor John R. Vane received the Nobel Prize for his discovery of the significance of prostacyclin in pulmonary circulation.
In the 90s were developed the first intravenous prostanoids, epoprostenol and bosentan, which they are endothelin antagonists.
In 2000-2002, BMPR2, a gene responsible for the familial form of pulmonary arterial hypertension, was recognized. Studies also started for other derivatives of prostacyclin ( iloprost, treprostinil, beraprost).
2003-2004, guidelines and the first IAP treatment algorithm based on evidence of Pulmonary Hypertension were approved at the International Conference of Venice.
From 2005 until today, new studies have been made, new drugs and therapies have been produced, whereas the research has taken serious parameters to give us new therapeutic ways.
In the last year, 2013-2014, we have in our “quiver” two new important drugs, that are expected to come out in our country in mid 2014.
Definition
Pulmonary Hypertension (PH) has nothing to do with hypertension. Hypertension is the increase of blood pressure within the arteries of the entire body except the lung arteries. On the contrary, the Pulmonary Hypertension involves only the lungs arteries.
The arteries of the lungs react differently from the other arteries of the body. For example, the reduction of blood oxygen causes vasodilation of the arteries of the body and vasoconstriction of the arteries of the lungs.
This explains why climbing at a tall mountain with an altitude of over 1,000 meters, where the atmospheric air has a lower oxygen content, creates conditions of vasodilation in peripheral vessels resulting to the decrease of blood pressure and causes pulmonary vasoconstriction of blood vessels leading to increased pulmonary pressure.
The normal pressure of blood within the arteries of lungs does not exceed 20-25 mmHg. At a healthy person, the pressure increases approximately up to 20 mm Hg (millimeters of mercury ) and decreases up to 5 mm Hg. Pulmonary artery pressure (often indicated as mPAP [middle pulmonary artery pressure]) is the average of the higher and lower pressures. Diagnosis of pulmonary hypertension is set if the middle pulmonary artery pressure exceeds 25mmHg at rest, with normal pressure in the pulmonary capillaries during right heart tubing ( The increase in pulmonary pressure can reach and surpass the levels of blood pressure, which means to reach and surpass the 120 mmHg. The most common Causes of Pulmonary Hypertension are:
• Chronic lung diseases, such as chronic bronchitis leading to chronic obstructive lung disease, and fibrosis of the lung. Important factors in the worsening of the situation are infections and smoking.
• Diseases of the veins of the legs, such as varicose veins, thrombosis and thrombophlebitis. Blood clots formed within the veins can easily be detached and create plugs in the bloodstream that reach small arteries of the lungs, then clog and destroy them, thereby increasing the pressure of the blood within the arteries of the lungs.
• Chronic diseases of the heart, such as stenosis or mitral insufficiency and heart failure. These disorders cause an increase in pressure within the left ventricle of the heart and then they are transmitted to the veins and arteries of the lungs. This creates the Pulmonary Hypertension with a cardiac origin.
• Some congenital heart defects, such as the ventricular septal defect and open Botallo duct when the damage is large.
• Living at an altitude of over 8,000 feet (2,438 meters) or climbing or hiking at an altitude of over 8,000 feet (2,438 meters)
• Connective tissue diseases, such as Scleroderma or Lupus.
• Sleep apnea and other sleep disorders.
• Sickle cell anemia, Chronic liver disease (cirrhosis) and AIDS.
• Pulmonary Hypertension occurs as a side effect of certain substances, such as anorexia, anti-obesity drugs and cocaine.
• Finally, Idiopathic Pulmonary Hypertension, which is responsible for 40 % of cases P.A.Y. and is more common in young women (up to 3.5:1 compared with men) with a mean age of 36 years at diagnosis. Idiopathic situation created by unknown causes is basically where there is thickening of the wall of the pulmonary arteries and decrease until disappearance of the internal diameter.
3. Symptoms
Symptoms of Pulmonary Hypertension in its early stages cannot be understood for months or even years. However, as the disease progresses, they deteriorate.
The symptoms include:
• Shortness of breath (dyspnoea), initially during exercise and finally at rest.
• Distress.
• Dizziness or fainting (heart failure).
• Pressure or pain in the chest.
• Persistent dry cough and hoarseness.
• Swelling (edema) of the ankles, your legs, and finally in the abdomen (ascites).
• Blue color on the lips and on the skin (cyanosis).
• Racing pulse or heart palpitations.
4. Classification of Pulmonary – Categories P.H
Classification of Pulmonary Hypertension (World Health Organization )
Pulmonary Hypertension is an important disease that concerns a respectable percentage of population: 30-50 persons per million population, according to the estimates of experts. Divided into two main categories: Primary Pulmonary Hypertension, whose rationale is not known, and Secondary Pulmonary Hypertension, the appearance of which is attributed to different causes.
Group 1 : Pulmonary Arterial Hypertension
A. Idiopathic (primary)
– Familial.
– Related to: vascular connective tissue disease, systematic communication – pulmonary circulation, portal hypertension, infection by HIV, drugs / toxins (eg. anorexia, rapeseed oil, L- tryptophan, methamphetamine, cocaine).
– Other conditions: thyroid disorders, thisafrismoseis, hereditary hemorrhagic telangiectasia, hemoglobinopathy, myeloproliferative disorders, splenectomy.
– Significant venous or capillary involvement.
B. Pulmonary veno-occlusive disease
C. Pulmonary – capillary hemangiomatosis
– Persistent pulmonary circulation of the newborn.
Group 2: Pulmonary Venous Hypertension
– Cardiomyopathy left cavities.
– Valvular Heart Disease of the left cardiac cavities.
Group 3: Pulmonary Hypertension associated with hypoxemia
– Chronic obstructive pulmonary disease.
– Interstitial lung disease.
– Sleep breathing disorders.
– Disorders with alveolar hypoventilation.
– Sojourn at an altitude.
– Developmental abnormalities.
Group 4 : Pulmonary Hypertension due to chronic thrombotic or embolic disease
– Thromboembolic obstruction of proximal pulmonary arteries.
– Thromboembolic obstruction of distal pulmonary arteries.
– Pulmonary embolism (tumors, parasites, foreign material).
5th group: Miscellaneous
– Sarcoidosis, pulmonary histiocytosis, lemfangeiomatosi, compression of pulmonary vessels (adenopathy, tumors, mediastinal fibrosis).
5. Functional classification (Evaluation of the severity of P.H.).
The severity of symptoms and the degree of restriction of physical activities in patients with P.H. is evaluated based on the Functional Stadium during the classification of the World Health Organization (WHO-FC). Such an evaluation provides useful information about the current level of physical function, correlates with prognosis and may help guide decision-making about treatment or revising therapy.
There are four Functional Stages, Stage I is the least severe and Stage IV is the most advanced, in which patients with P.A.H. show weakness whenever operating a physical activity.
When P.H. is once diagnosed, it is necessary to classify the disease based on the “functional classification system” developed by the New York Heart Association. The system is based on patient reports about how much natural (physical) activity can take comfortably before any symptom become perceptible.
The Category I includes patients who did not have any kind of symptoms and to whom ordinary physical activity does not cause fatigue, palpitation, shortness of breath or chest pain.
The Category II includes patients who feel comfortable in resting state, but have symptoms when they are having an ordinary physical activity.
The Category III includes patients who feel comfortable in resting state, but have symptoms when they make less effort than usual.
The Category IV includes patients who have symptoms even in the state of resting.