Lung Diseases

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Primary function of lungs is a blood oxygenation, and secondary the maintenance of acid-base balance through regulation of CO2 concentration.


Lung disorders are divided into:


A/ Obstructive with increased resistance to the air flow in respiratory passages, and thereby limited ventilation of alveoli, which can be global or partial, leading to disruption of distribution. Bronchial asthma and chronic bronchitis are classical examples.


Bronchial asthma is due to allergy to inhaled antigens, i.e. pollen, which causes inflammation of bronchial mucosa with subsequent release of histamine and SRS-A, slow reacting substances of anaphylaxis, that bring about contraction of bronchial muscles, mucus secretion, and increased permeability of blood vessels causing edema. Microorganisms in the mucus become antigens as well, and bronchial asthma turns into chronic bronchitis.

Many consider bronchial asthma a contraindication for cell transplantation but of all lung diseases it has been one most frequently treated by this method. Review of 88 cases, 46 males, 42 females, majority between 60 and 80 years of age, treated by fresh cell transplantation of lungs, adrenal cortex, thymus, mesenchyme, intestine, placenta, gonads, heart, brain cortex, artery, but also liver, diencephalon, mesencephalon, anterior lobe of pituitary, spleen, over 3 years, each one of them for a classical reason because ‘all other treatment methods had failed’, showed an absence of any allergic reactions after the treatment, an absence of status asthmaticus and only 3 instances of asthma attack after cell transplantation. A self-evaluation of the results was requested of all 88 patients, and 56 responded: 36 patients reported an improvement of asthma, while 11 reported improved general well-being but no improvement of asthma. All patients that reported an improvement stopped taking cortisol. One patient reported deterioration of his asthmatic condition, and 8 patients did not notice any change.


In selection of cell transplants for treatment the author of this report gives credit to P. Janson, who found that cell transplants of spleen function as an excellent anti-allergy treatment, causing desensitization, and to P. Niehans, who treated asthmatics always with hypothalamus, lungs and placenta, and credited S. Reckeweg with using spleen, kidneys, adrenal cortex, placenta and hypothalamus, for his patients. As a precaution all patients received 12 hours before treatment a combination of antihistamin, and an injection of cortisone. Based on their experience the patients with cor pulmonale with dyspnea at rest and with advanced emphysema are not be accepted for treatment by cell transplantation. Seven case histories are included. [295]


A 65 years old female suffered from bronchial asthma for over 20 years due to allergies to dust and various kinds of grass. She got worse in Spring and Fall when she developed attacks of bronchitis with fever. Five years before this report she developed status asthmaticus for the first time. Laboratory testing proved her allergies as well as immune deficiency. She was treated by gamma-globulin as necessary. As her condition was not improving over 21 months a cell transplantation of mesenchyme, lungs, adrenal cortex, diencephalon, thymus, was carried out. During 3 years of floow-up she has not had a single asthma attact, her immunoglobulins, including IgE, were within normal limits, and other tests indicated no humoral or cellular immune deficiency. [309]


Another concept of asthma treatment calls for cell transplantation of thyroid, thymus, posterior lobe of pituitary, adrenal medulla, to which sometimes liver, parathyroid, anterior lobe of pituitary, medulla alba of brain, is added. [328]


Cystic fibrosis, or mucoviscidosis, is the most frequent lethal AR disorder among Caucasians with incidence 1:2000. Pathogenesis is due to the deficiency of gene product CFTR, ‘Cystic Fibrosis Transmembrane Conductance Regulator’, which regulates movement of chloride ions across Cl- channel. One type of 850 types of mutations of CFTR gene has been with us for 50,000 years. There is a malfunction of transport of fluids and electrolytes in exocrine epithelial cells, which causes an increased secretion of sweat in sweat glands with higher concentration of Cl- than Na+. There is an increased viscosity of more profuse mucous secretions in small bronchi, because fluids are absorbed rather than secreted, and such protein-rich secretions are the best medium for the bacterial growth, in particular Pseudomonas, that leads to slowly developing chronic pathologic changes of lung, i.e. bronchial obstruction with atelectasis, emphysema, bronchopneumonia, bronchiectases, fibrosis, pneumothorax, cor pulmonale. That goes hand in hand with insufficiency of exocrine pancreas due to obstruction of pancreatic ducts with viscous secretions that causes chronic pancreatitis, and sometimes liver dysfunction, while in genital tract with blockage of ductus deferens and infertility in men, or lowered fertility in females. In intestines meconium becomes thickened and gluey and is not eliminated the usual way, causing meconium ileus instead in 10% of newborns. In nose polyps and chronic sinusitis develop. Fetal precursor cell transplantation of lung, exocrine pancreas, intestine, skin, mesenchyme, placenta, is recommended.


Senile lungs with weakened lung retraction force causes obstruction disorder as well. Aging changes mainly the structure of elastic fibers so that their retraction power dwindles, while the proportion of collagen increases. There is a decreased number of alveolar septa, dilatation of alveolar ducts, reduction of capillary network in alveoli, calcification of cartilagineous bronchial skeleton.


B/ Restrictive with reduction of diffusion area due to loss of functioning lung tissue.


Emphysema is a classical example, where along with reduced diffusion area there is also a reduced count and increased volume of alveoli. ‘Centrilobular emphysema’ is brought on by obstructive lung disorders, while in ‘panlobular emphysema’ there is loss of interalveolar septa as well.


Primary atrophic, or senile, emphysema has been treated with success by fetal cell transplantation of placenta, lung, mesenchyme, liver, thymus, hypothalamus, and cardiomyoblasts if cor pulmonale is present.


In some patients there is a alpha1-antitrypsin deficiency which normally inhibits the effect of proteases. Such patients suffer from emphysema 15 times more frequently that normal population. This enzyme is produced in liver, and mutations can disrupt its secretion or function. This enzymopathy leads in 60% of patients to disruption of lung tissue and thereby loss of its elasticity. In smokers the alpha1-antitrypsin is oxidized and thereby blocked, so that emphysema develops even in genetically healthy individuals. Dominance of elastases leads to breakdown of elastic lung fibers with inflammation.


Limited chest motion, paresis of diaphragm, increased pleural space with pleural effusion, pleural adhesions, or pneumothorax, belong to this group, too.


C/ With impaired perfusion due to by restrictive, obstructive and circulatory disorders, where despite adequate oxygenation and removal of CO2 from blood in alveoli there is still decreased concentration of gases in blood, and circulatory overload with serious consequences for the right heart.


D/ With impaired diffusion due to an increased diffusion distance with lung edema, where increased intravascular pressure leads to exsudation of plasma into lung interstitium and eventually into alveoli, or in pneumonia where edema and increased production of fibrotic tissue causes thickening of septa between alveoli and blood capillaries, or with pulmonary fibrosis where fibrotic tissue pushes capillaries away from alveoli, or with reduction of diffusion area such as in atelectasis or pulmonary infarct.

Lung fibrosis develops after inflammation of connective tissue, i.e. in collagen diseases, or after inhalation of azbest or silica dust, or sometimes without apparent reason, i.e. Hamman-Rich idiopathic lung fibrosis,


E/ Those caused by malfunction of regulatory neurons in respiratory center, as well as motoneurons, nerves, neuromuscular synapses and respiratory muscles.


Overall, lung diseases have been treated seldom by cell transplantation in the past for reasons unknown.