Biomedical subjects
Publications and source records attributed to W T Ulmer.
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The discussion about influence of air pollution on health is loaded by special problems: methods are not always adequate, special interest exists of the general population and of politicians, more than 100 substances are involved. There is no ascertained knowledge about systemic actions of air pollutants by diffusion or resorption. Local action on bronchopulmonary system can cause or deteriorate otherwise provoked diseases. There are no ascertained results that general air pollution is really the cause of diseases. Deterioration of airways obstruction takes place on patients with hyperreactivity of the airways in the range of 2,5 mg/m3 SO2. It is possible that very sensitive patients also react against lower concentrations. These results were shown on rectangular increases of concentration. Slower increases of the concentrations show less or no effect. The same reactions can be seen by exposure against cold air or other unspecific challenges of these patients. The published data on premature death are in disagreement with corresponding experimental results. For the development of lung cancer the knowledge of tobacco smoking habits is indispensable. In the future long-term studies with high response-rates are necessary. Our basic knowledge today is sufficient to perform such studies. The industrialized society has to solve such questions which also interfere with other more extended problems.
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The influence of tracheal lavage with an allergen on the airway response to bronchial challenge with histamine, acetylcholine, and ascaris extract was investigated in 36 dogs. High histamine concentrations were measured in the tracheal solution after lavage with allergen. This amine, released on the mucosal surface, was observed in only very small concentrations in the circulation. Airway response to acetylcholine inhalation was significantly increased after tracheal lavage with allergen. This hyperreactivity of the lower airways induced by tracheal lavage with an allergen suggests that a reflex mechanism is involved. After histamine inhalation a significantly larger antigen-induced histamine release to tracheal lumen was observed. No influence on airway response was found after tracheal lavage with H2O.
The influence of tracheal lavage in a restricted area, with a proteolytic enzyme (Pronase) on the bronchial response to challenge with ACH and AE was studied in 15 dogs. Histamine concentrations measured in the tracheal liquid after lavage with Pronase were smaller than the values after tracheal lavage with allergen. Airway response to ACH inhalation was significantly increased after tracheal lavage with Pronase. Effects of proteolytic enzymes and allergens on the tracheal wall are compared. Allergens and proteolytic enzymes evidence a different mode of action in increasing reactivity of peripheral airways.
The influence of tracheal lavage with compound 48/80 on the bronchial response to challenge with ACH and AE was studied in 24 animals. Furthermore, the effect of i.v. administration of 48/80 was compared to its administration into the tracheal lumen. No increased histamine liberation was detected in the tracheal fluid after lavage with 48/80, nor was an influence on the bronchial response observed. These observations were the same as those described for tracheal lavage with water. The same amounts of this secretagogue induced, after i.v. administration, a high histamine release which correlates significantly with blood pressure decrease.
The influence of tracheal lavage with histamine, and of i.v. administration of histamine on bronchospastic response was studied in 16 dogs. Airway response to acetylcholine inhalation was significantly increased after tracheal lavage with high concentrated histamine solution (1%). No influence on airway response was found after (1) tracheal lavage with lower concentrations of histamine and (2) its i.v. administration. The clinical importance of these manifestations is discussed.
Under physiological conditions human bronchial mucus contains an elastase-specific inhibitor which is quite different from hitherto known inhibitors: alpha 1-antitrypsin, HI-30, and BSI-TE. In bronchial mucus of 100 patients suffering from obstructive airway disease the amount of this inhibitor specific against elastase from both pancreas and polymorphonuclear neutrophilic leucocytes was measured. A group of 18 patients showed no inhibitor in their native mucus rather than free elastolytic activity. Another group of 82 patients had no elastolytic activity in their native mucus but free anti-elastolytic activity together with varying amounts of elastase-specific inhibitor bound to proteases. In a total of 20 cases from both groups the inhibitor was not detectable, neither in a free nor in a complexed form. Presuming that there is no hereditary deficiency involved, a strong importance of inactivating reactions such as oxidation is concluded.
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Antigen-induced bronchoconstriction can be brought about by provocation of either the upper or lower airways. Rising plasma histamine concentrations can be measured at the time of an increase in airway resistance and at the onset of bronchoconstriction. Relatively high histamine concentrations can be measured in the mucus from patients with chronic obstructive bronchitis. The arterial plasma concentration of histamine was significantly increased in these patients. Histamine administered to a limited area of the tracheal mucosa can induce an increase in airway sensitivity to acetylcholine, but not to allergen or histamine. The role of histamine release in antigen-induced reflex bronchoconstriction originating from the upper airway is questioned.
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Some types of pneumoconiosis, such as asbestosis, are characterized by marked restrictive functional patterns. Treatment is begun when definite arterial hypoxemia appears, since the inhalation of oxygen clearly lowers pulmonary artery pressure. It is also important that the onset of concomitant airway obstruction is recognized promptly. From the sociomedical standpoint the most significant pneumoconiosis continues to be the miner's anthracosilicosis. The functional pattern of this pneumoconiosis is clearly airway obstruction, and such anthracosilicotic airway obstruction responds like all other forms of airway obstruction to antiobstructive therapy. The fundamentals of this therapy, which is based on the use of bronchodilators, adrenal cortical hormones and antibiotics, are described.
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In a clinical study pure theophylline in retard pellets form (Afonilum retard, 1 capsule contains 250 mg theophylline in SR-form) was tested over 6 days in 2 groups with 5 patients each. The effect of theophylline in patients with severe airway obstruction (group A: Rt = 9,0 cm H2O/l/sec) and with slight airway obstruction (group B:Rt = 3,5 cm H2O/l/sec) should be studied as well as the possible reduction of beta 2-sympathomimetics in form of aerosol. The bronchospasmolytic effect of theophylline was registered after 3 days medication. Beta 2-sympathomimetics could be reduced from 12 lifts/day to average 2-4 lifts/day at the end of study. Theophylline serum levels are at 7,5 microgram/ml (group A, means) and at 11,0 microgram/ml (group B, means).
There is a statistically strong correlation between the increase of the histamine concentration in the arterial plasma and the increase of airway resistance. The histamine causes a reflex bronchoconstriction on the sensory receptors. Histamine in low concentration increases the unspecific reaction in the bronchial system. This can also be achieved using low concentrations of allergen aerosols. Patients with chronic obstructive bronchitis show high concentrations of histamine in the sputum. The bronchoconstrictive potency of this histamine was found to be not always active. Higher concentrations of histamine can be liberated by washing the inner surface of the bronchial tree. Histamine injected in similar concentrations as that measured in the sputum causes bronchoconstriction. There should be high concentrations of histamine receptors as well as mast cells near the surface of the mucosa of the bronchial wall. There are many questions remaining open, which will be discussed.