My Canadian Pharmacy: Deliberations about Small Airways Disease

airwayThere are as yet few studies correlating early abnormality of lung function with morphologic changes in the lung. Comparison between these studies demonstrates some similarities but also some marked differences.

The TPS correlated significantly with the MMFR and V50. However, in contrast with the results of Cosio et al, the relationship to the slope of phase 3 was poor. This was mainly due to three patients with marked small airways narrowing and high TPS (mean TPS = 165) who had normal slopes (mean slope 113 percent of predicted). Although the TPS was high, inflammation was not particularly marked in these lobes. The best correlations with lung function were obtained when only the inflammation score was used. This suggests that the presence of inflammation is so important that it overshadows all other variables which produce airflow limitation. It is important to recognize that, as suggested by Hogg, inflammation per se may be responsible for flow limitation rather than airway narrowing consequent upon inflammation. It appears that inflammation either through altered bronchiolar wall dynamics or lumenal exudate (which may also alter surfactant), can produce abnormal time constants. Of the four variables comprising the TPS in this study, only inflammation is likely to be a reversible component. Since inflammation is best correlated with abnormalities in the SBNT, the reversibility of abnormality of the SBNT following cessation of smoking’ could be explained by reversibility of tobacco-induced bronchiolitis. Improve lung function with remedies of My Canadian Pharmacy.

In this study, the correlations between the small airway measurements and the lung function tests were generally poor with only the correlation between the IB and V50 reaching statistical significance. In a previous study, the correlation coefficients were similar in magnitude but were significant (at the 5 percent level) for the IB/EAA and FEVi, MMFR, and CVWC. The nonsignificant correlations between the small airways measurements and lung resistance in this study are in marked contrast to the findings of Niewoehner and Kleinerman who obtained a correlation coefficient of 0.89 (p <0.001) between IB and pulmonary conductance. The reason for this difference in results is not clear. In this study, the lungs were fixed at total lung capacity (TLC), whereas most relevant measurements of lung function are made at 50 percent vital capacity or less. It is likely that different pressure-diameter relationships exist in airways with different types and degrees of airway lesions in addition to the effects through interdependence of altered elastic recoil of the surrounding lung in emphysema so that equal diameters at TLC do not necessarily indicate equal diameters at lower lung volumes in different lungs. Thus, the poor correlation between the small airway measurements and lung function may be a result of the method of fixation.

Several components of the large airway wall were measured to see if correlations with forced expiratory flow rates and lung resistance existed. The Reid Index is a logical choice since enlargement of the gland layer internal to the cartilage may cause luminal narrowing. However, the degree of glandular hyperplasia observed in patients with chronic bronchitis can be calculated to cause but little encroachment on the lumen. Nevertheless, the Reid Index was significantly correlated with the FEVi in this study. This is in line with the findings of McKenzie et al but contrary to some others. Thurlbeck et al found a significant correlation between the Reid Index and the MMFR. If the Reid Index is only indirectly related to airway obstruction, then better correlations may be expected between estimates of total gland volume and tests of airflow limitation. This was found by Oberholzer et al, but not in this study. The Vv muscle was uniformly poorly related to lung function tests and may be of importance not in the absolute degree of airflow limitation, but rather its reversibility. Lung function may be enhanced and magnified with My Canadian Pharmacy.

lung function testsThe results of this study also highlight some of the problems inherent in the various measurements of small airway dimensions. The main difficulty lay not with the actual measurements which can be performed very precisely, but rather where to take the measurements in any individual airway. Observers may also differ in which airways they classify as respiratory bronchioles, and therefore, exclude from measurement. This certainly occurred in the present study as the number of airways measured by observers 1 and 2 differed by an average of 11 percent.

Although in general the Vvsa was the most reproducible measurement, there exists the possibility of occasional major discrepancy as illustrated by the one lung which, according to the inclusion or exclusion of a single airway, gave widely varying results. The Vvsa is highly sensitive to inclusion of airways at the upper range of small airway diameters, eg, one airway of 2 mm internal diameter has the same area as 16 airways of 0.5 mm diameter (if transversely sectioned). The reason for the marked difference in the results of the Vvsa between this and a previous study2 could not be completely explained. However, a decrease of Vvsa out of proportion to changes in Na and mean IB have been observed in chronic bronchitis and emphysema, and it is possible that the lungs of this series were more abnormal. A greater variability between lungs was observed for the Vvsa than for the other measurements.

The IB and IB/EAA measurements were reasonably reproducible within observers although being significantly different between observers. There was less variability in the IB than had been found previously, but there were also fewer lungs. The variability of the IB/EAA was only slighdy less than for the IB. However, the IB/EAA still has the advantage of being independent of shrinkage. It was of interest to see that for a given degree of pathologic involvement as measured by the TPS, the dimensions of the small airways in the lobes obtained at surgery were smaller than in the lungs obtained at autopsy. The lobes were formalin-inflated immediately following surgical removal, and bronchiolar muscle tone may still have been present. This suggests that bronchiolar diameters in lungs or lobes obtained by different means may not be directly compared. Although significant correlations were found between the TPS and IB and IB/EAA, at least in the resected lobes, the differences in pathologic involvement between groups 1 and 2 could not be detected in either the autopsy lungs or the lobes using the airway measurements. Thus, the early and probably largely reversible changes of small airways disease would escape detection if airway measurements were relied upon.

The TPS scored without a connective tissue stain was less reproducible both within and between observers than the airway measurements, and this was largely due to the inconsistent scoring of the degree of fibrosis. Reproducibility was much improved by the use of a special stain, although a significant difference between observers remained. Indeed, there was no significant difference between the TPS with and TPS without the special stain, and thus, it

mainly seemed to improve the correlation within observers, the pattern of observer 2 scoring higher than observer 1 being maintained. Nevertheless, it was shown that the reproducibility of this subjective method was on par with that of the “objective” measurements. The importance of the consistency in scoring inflammation is obvious in the light of the results of the structure-function correlations.

The results of this study suggested that the TPS has some important advantages over direct measurements of small airway dimensions. It is independent of the lung volume at which it is scored, independent of shrinkage during processing, able to detect early pathologic changes, and as reproducible as the measurements when a connective tissue stain is used. Probably, as a result of these advantages, better correlations with lung function tests can be obtained. Furthermore, the results of this study suggest that the TPS can be abbreviated with advantage to include only the score of inflammation which was found to be the most important determinant of abnormalities of the SBNT.