Airway Structural Changes Research Articles

The Future of Asthma Treatment

In the past few years, significant progress has been made in the treatment of asthma with the development of bronchodilators with longer durations of action, more concentrated inhaled steroid formulations and new modes of administering antiasthma medication. Furthermore, the hey role of education in the management of asthma has been emphasized and many educational programs have been established. The recognition of the role of airway inflammation and structural changes in the physiopathology of asthma has led to a re‐evaluation of asthma treatment guidelines. Anti‐inflammatory drugs are now considered the mainstay of asthma therapy. An unprecedented number of new, potentially helpful agents have been developed and will soon be available. Among other expected developments are the identification and possible correction of genetic abnormalities responsible for the tendency to develop asthma and atopy, and prevention or functional and structural airway changes. This last goal will be achieved by improved environmental control, earlier use of more powerful and safe anti‐inflammatory agents, as well as an increased involvement on the part of the asthma patient in treatment.

Platelet-derived growth factor and its receptor in lungs from patients with asthma and chronic airflow obstruction

The airway walls of patients who have asthma or chronic obstructive pulmonary disease (COPD) are thickened by an increase in the amount of smooth muscle and connective tissue. Platelet-derived growth factor (PDGF) is a candidate cytokine for this increase because it can produce smooth muscle proliferation in vitro. The present study was designed to examine the expression of PDGF and its receptor (PDGFR) in lungs from six asthmatics, six patients with COPD, and six patients with normal lung function. PDGF was immunolocalized to tissue macrophages, but the number of PDGF-positive cells was similar in all three groups. PDGFR-beta was rarely expressed on interstitial cells, and, occasionally, on bronchial epithelium. Northern blotting, performed on tissue from the same groups, showed a positive correlation of PDGF(B) with PDGFR-beta mRNA level (r = 0.74, P < 0.001) and a higher abundance of PDGF(B) and PDGFR-beta mRNA in the asthmatics vs. the COPD (P < 0.05). We conclude that PDGF and its receptor are expressed in human lungs but do not correlate closely with the structural changes in diseased airways.

Airway Inflammation and the Pathogenesis of Asthma

Airway inflammation has been recognized for more than l00 years to be present in the airways of patients with severe asthma. Much more recently, airway intlammation has been identified to be central to the pathogenesis of all asthma. The inflammation is of a characteristic type, with the presence of activated eosinophils, mast cells and lymphocytes in bronchoalveolar lavage fluid and airway biopsies from patients with even mild asthma. Stimuli that are known to worsen asthma, such as inhaled allergens, also increase the numbers of mast cells and cosinophils in asthmatic airways. In addition, treatment with inhaled corticoteroids - the most effective treatment for asthma - improves symptoms and reduces the numbers of eosinophil s, mast cells and lymphocytes in the airways. The precise functions of the cells in promoting inflammation and causing asthma symptoms has not yet been fully elucidated. However, it is very likely that eicosanoids, such as the cysteinyl leukotrienes, are produced by eosinophils and mast cells and are a major cause of bronchoconstriction in asthma. Also, these inflammatory cells can produce proinflammatory cytokines, such as granulocytc-macrophage colony-stimulating factor. interleukin (IL) 3 and IL-5, which may promote continuing inflammation in the airways. Lastly, the persisting inflammatory cell infiltrate and products re leased from these cells arc very likely the cause or the airway structural changes characteristic of asthma, such as epithelial damage, goblet cell hyperplasia. smooth muscle thickening and deposition of collagen below the basement membrane. These changes have been suggested tn he the cause of airway hyperresponsiveness in asthma. An improved understanding of the precise mechanisms by which airway inflammation is initiated, propagates and causes airway damage will hopefully allow more precise treatment strategies to he developed for asthma than currently exist.

Pulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia.

Despite four decades of investigation, the function of pulmonary neuroendocrine cells (NEC) remains unclear. Since NEC secretory products may influence airway growth or differentiation or alter airway smooth muscle tone, increased numbers of NEC seen in bronchopulmonary dysplasia (BPD) may be partially responsible for the genesis of the structural and pathophysiological alterations seen in this disease state. Changes in airway structure were studied in six infants dying with BPD and six conceptional age-matched control infants dying of noncardiopulmonary disease. Changes in bombesin-, calcitonin-, and serotonin-immunoreactive NEC were quantified in lung specimens from three infants who died at 2 months of age with severe BPD and three conceptional age-matched controls. There were no differences in either bronchiolar or bronchial airway epithelial areas, but significant increases in bronchiolar (1.8-fold) (P < 0.001) and especially bronchial smooth muscle (2.5-fold) (P < 0.001) were documented in infants with BPD. Few bombesin-, calcitonin-, and serotonin-immunoreactive cells were identified in cartilaginous airways; however, there was a clear increase in the total number of bronchiolar immunoreactive cells in infants with severe BPD (28.5 +/- 11.2 cells/mm airway epithelium) compared to control infants (4.5 +/- 4.9) (P < 0.05). Our results confirm that airway wall composition does change in BPD, but there is either no or an inverse correlation between NEC number and airway epithelial and smooth muscle areas and cell numbers. The role of NEC secretory products in airway smooth muscle growth and function requires further investigation.

Mucosal Permeability and Smooth Muscle Function in Asthma

The changes in airway structure that occur in asthma are characteristic of a chronic inflammatory process that involves tissue covered by a mucosal surface. This article reviews the inflammatory process and presentation of evidence that structural changes seen in asthmatic airways are a result of this response. The contribution of the airway muscle and epithelium to the abnormal function of asthmatic airways is also reviewed.

Validation of an &lt;italic&gt;in vivo&lt;/italic&gt; Aerosol Probe Technique by Measurements of Deposition and Morphometry in Excised Human Lungs

Structural changes of the small airways (< 2 mm diameter) and the pulmonary airspaces occur early in the pathogenesis of chronic obstructive pulmonary diseases (COPD). We have previously shown that the rate of deposition of a monodisperse aerosol during breath holding can be used to determine a mean effective airspace dimension (MEAD) for lung airways. While in vivo MEADs were consistent with morphometric models of the human lung, direct confirmation of the method with morphometric measurements in the same lungs was lacking. Experiments in excised human lungs were initiated to validate the method and to determine the influence of various lung dimensional indices on the parameters obtained from the aerosol probe measurements. Strong correlations were found between aerosol and morphometric indices in a group of 23 lungs, providing increased confidence for applications of aerosol probes in epidemiological and clinical evaluations.

Oxidative Metabolism of Alveolar Macrophages from Young Asymptomatic Cigarette Smokers: Increased Superoxide Anion Release and Its Potential Consequences

Alveolar macrophages (AM) have been implicated in the pathogenesis of the centrilobular emphysema related to cigarette smoking. Clusters of AM lodge in the bronchioles of smokers before the development of emphysema, and persist as tissue destruction and fibrosis progress. 1 Niewoehner DE Kleineman J Rice DB Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med. 1974; 294: 755 Crossref Scopus (681) Google Scholar , 2 Cosio M Ghezzo H Ghezzo JC et al. The relations between structural changes in small airways and pulmonary function tests. N Engl J Med. 1978; 298: 1277 Crossref PubMed Scopus (589) Google Scholar While these observations support a role for AM in the induction of emphysema, the mechanism by which AM may cause emphysema is not known.

The relations between structural changes in small airways and pulmonary-function tests.

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P less than 0.05) by tests for closing capacity, the volume at which air and helium flow ere equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed.

Cystic fibrosis of the pancreas: Structural changes in peripheral airways : J. R. Esterly and Ella H. Oppenheimer. Thorax 23:670 (November), 1968

Cystic fibrosis of the pancreas: Structural changes in peripheral airways : J. R. Esterly and Ella H. Oppenheimer. Thorax 23:670 (November), 1968

Cystic fibrosis of the pancreas: structural changes in peripheral airways.

Emphysema and bronchiolar obstruction were found in the necropsy specimens from 42 of 84 patients with cystic fibrosis of the pancreas. Significant parenchymal destruction could be demonstrated in only three cases. In contrast, widespread severe dilatation of respiratory bronchioles and alveolar ducts was present in 29 of the older infants and children, and less extensive, moderate dilatation was seen in an additional 13 cases. Eleven patients also had morphological evidence of bronchiolar scarring and stenosis. Because of the chronic pulmonary infection in these patients, it is unlikely that the structural changes in peripheral airways are clinically significant. Nevertheless, this widespread dilatation may be responsible for the physiological and radiographic evidence of emphysema. Furthermore, the lobular dilatation in these young patients may be an antecedent of destructive emphysema in the adult.