Human Lower Respiratory Tract Research Articles

Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man.

Substance P (SP)-immunoreactive nerve fibres were searched for at all levels of both fetal and adult human lower respiratory tract. Because the demonstrability of substance P immunoreactivity varies between different animal species, rabbit pulmonary tissue was also subjected to SP immunohistochemistry. Human irises and corneas served as positive human controls. The specimens were taken from 10 human lungs during pulmonary operations. Tracheal tissue was obtained from three patients during bronchoscopy. Five fetal human lungs were examined. Human specimens examined included the trachea, main bronchi, segmental bronchi, and peripheral pulmonary tissue. In addition, the tracheobronchial tissues of four rabbits were studied. SP immunoreaction was demonstrated in formaldehyde-fixed cryostat sections by either the indirect immunofluorescence technique or the peroxidase-antiperoxidase procedure. Both monoclonal and conventional antibodies to SP were tested. In the rabbit SP-immunoreactive nerves were found in both the submucosa and the smooth muscle layer of the main bronchi and trachea. Specimens from human trachea, bronchi, and bronchioli were all negative. Since the SP immunoreaction was easily demonstrated in both human cornea and human iris, it was concluded that there are no SP-immunoreactive nerves in the human pulmonary tissues or that their SP content is very low and below the sensitivity of all the techniques used.

Smokers Do Not Have Less Functional Alpha1-Protease Inhibitor in Their Lower Respiratory Tracts Than Nonsmokers

Cigarette smoking is the major risk factor in the development of pulmonary emphysema, a condition thought to result from an imbalance between the elastase and antielastase levels in the lungs. An increased number of neutrophils and alveolar macrophages in the lungs of smokers could account for an elevation of their elastase burden. A decreased level of functional alpha1-protease inhibitor (alpha1-PI) has been reported in the bronchoalveolar lavage (BAL) fluid from smokers as compared with nonsmokers. 1 Gadek JE Fells GA Crystal RG Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans. Science. 1979; 206: 1315-1316 Crossref PubMed Scopus (264) Google Scholar , 2 Carp H Miller F Hoidal JR Janoff A Potential mechanism of emphysema: α1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA. 1982; 79: 2041-2045 Crossref PubMed Scopus (268) Google Scholar We determined binding and inactivation of 3H-porcine pancreatic elastase and 125I-human neutrophil elastase by alpha1-PI in BAL from volunteers; we also measured the inhibition by BAL of porcine pancreatic elastase-catalyzed solubilization of 3H-elastin. The mean levels of functional alpha1-PI in the BAL of smokers were comparable to those of nonsmokers.

Catecholamine- and acetylcholinesterase-containing nerves in human lower respiratory tract

The innervation of human lower respiratory tract was studied with special emphasis on airways with sodium-potassium glyoxylic acid (SPG) and acetylcholinesterase (AChE) methods to demonstrate catecholamine-containing and acetylcholinesterase-containing nerve fibers. AChE-method revealed a rich network of cholinesterase positive nerves both inside the bronchial glands where they run around and between the acini, and the airway smooth muscle from secondary bronchi to terminal bronchioli. No AChE-positive fibers were found in connection with the blood vessels or within the epithelium of bronchi or bonchioli. The AChE-positive nerve fibers in bronchial smooth muscle greatly outnumbered those containing catecholamine. The SPG-method revealed the presence of adrenergic nerves from the level of secondary bronchi to that of terminal bronchioli. These nerve fibers were most abundant in bronchial glands, where their amount was equal and distribution similar to those of AChE-containing nerve fibers. Outside the glands adrenergic fibers were constantly seen in connection with the bronchial blood vessels in connective tissues surrounding bronchi. A few nerve fibers were also present in airway smooth muscle from the secondary bronchi to terminal bronchioli.

Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.

The current concepts of the pathogenesis of emphysema hold that progressive, chronic destruction of the alveolar structures occurs because there was in imbalance between the proteases and antiproteases in the lower respiratory tract. In this context, proteases, particularly neutrophil elastase, work unimpeded to destroy the alveolar structures. This concept has evolved from consideration of patients with alpha 1-antitrypsin deficiency, who have decreased levels of serum alpha 1-antitrypsin and who have progressive panacinar emphysema. To directly assess the antiprotease side of this equation, the lower respiratory tract of non-smoking individuals with normal serum antiproteases and individuals with PiZ homozygous alpha 1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract. These studies demonstrated that: (a) alpha 1-antitrypsin is the major antielastase of the normal human lower respiratory tract; (b) alpha 2-macroglobulin, a large serum antielastase, and the bronchial mucous inhibitor, an antielastase of the central airways, do not contribute to the antielastase protection of the human alveolar structures; (c) individuals with PiZ alpha 1-antitrypsin deficiency have little or no alpha 1-antitrypsin in their lower respiratory tract and have no alternative antiprotease protection against neutrophil elastase; and (d) the lack of antiprotease protection of the lower respiratory tract of PiZ individuals is a chronic process, suggesting their vulnerability to neutrophil elastase is always present.

Cigarette Smoking Induces Functional Antiprotease Deficiency in the Lower Respiratory Tract of Humans

Current concepts of the pathogenesis of emphysema suggest that it results from an imbalance of elastase and antielastase activity within the alveolar structures. Although emphysema that is associated with hereditary deficiency of serum alpha 1-antitrypsin conforms to this scheme, the major risk factor in the more common form of emphysema is cigarette smoking. A study was designed to evaluate the premise that cigarette smoking may be associated with an acquired, functional defect in lung alpha 1-antitrypsin. Determination of the antielastase activity of alpha 1-antitrypsin obtained from the lungs of smoking and nonsmoking individuals revealed a nearly twofold reduction in the functional activity of this elastase inhibitor in the lungs of cigarette smokers. These data suggest that cigarette smokers may lose some of the normal antielastase protective screen of the lower respiratory tract, making them more vulnerable to destructive lung disease.

Animal models of the asthmatic state.

Asthma is a common but poorly understood response of the lower respiratory tract of humans, which has and will require considerable investigative effort in order to define the basic mechanisms involved. Only limited studies can be done in asthmatic humans for safety reasons. Appropriate animal models are necessary to test hypoth­ eses of underlying mechanisms in this disease and to determine the significance of immunologic, pharmacologic, and cellular factors in human asthma. This discussion will include a brief review of the characteristics of asthma, the types of animal models that have evolved with comments on how tQese systems might relate to the human disease state, and, finally, summaries of some of the studies that have been carried out using these animal respiratory responses. Human asthma has been characterized clinically as recurrent wheezing dyspnea occurring in patients with bronchial hyperreactivity to a variety of stimuli. Physio­ logically asthma is characterized by reversible obstruction of the bronchi, such reversibility demonstrated most commonly by the administration of ,8-adrenergic agonists. An additional characteristic has been the clinical experimental observation that the hyperreactivity of the bronchi 'can be demonstrated by the administration of histamine, methyJcholine or, more recently, prostaglandin F2a (1). In minimal asthma there may be no pathologic changes observed in respiratory tissues but in asthma of long duration a thickened basement membrane and eosinophilia have been found at autopsy (2). Immunologically, one type of asthma is related to reaginic antibodies of the E class of immunoglobulins. This type of asthma may be associated with elevated serum concentrations of IgE (3) and the specific IgE antibodies may be demonstrated by in vivo skin tests or in vitro radioimmunoassay systems. Clinically, asthma is classified traditionally as either extrinsic or intrinsic. Extrin­ sic asthma is precipitated by inhalation of antigen, which reacts with IgE antibody fixed to mast cells in the lung with resultant mediator release. These mediators are 'Supported by USPHS Grants AI 11403 and AI 000 57 and the Ernest S. Bazley Grant.

Bronchoesophagology: Summaries of the Bibliographic Material Available for 1957

In 1957 bronchoscopy was used chiefly in the diagnosis of bronchogenic carcinoma and in the treatment of postsurgical complications. Esophagoscopy became firmly established in the diagnosis of esophageal disease with or without positive roentgen findings, as evidenced by its increasing use in hiatal hernia. Fundamental studies of pulmonary function, esophageal motility, and esophagogastric sphincteric mechanism received more attention, and basic research in the latter helped to clarify some of the controversial points regarding the hiatal sphincter. <h3>Experimental Studies</h3> Hilding¹studied the ciliary activity of the lower respiratory tract in humans and animals. Ciliary activity was found to continue many hours after death in humans, while the mucous blanket behaved less dependably. The flow of the ciliary stream in the bronchial tree of man was found to be generally upward against gravity and was very wide but rapidly narrowed as it approached the trachea. The velocity of ciliary flow was