Classification, definition and correlation between clinical and histologic staging of interstitial lung diseases

H. Y. Reynolds

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Increasingly, the classification of interstitial lung diseases depends on indirect tests that assess the amount of lymphocyte or PMN inflammation and macrophage activity in lung tissue (lung lavage, gallium lung scans, enzyme assays, and so on). Traditional parameters (clinical symptomatology, chest radiographic staging, and pulmonary physiology) can be less accurate, and open lung biopsy is used less frequently in the wake of endobronchial and transbronchial biopsies. Analysis of air-space cells and proteins/enzymes, retrieved by lung lavage, seems to be more precise for establishing the intensity of alveolar inflammation, especially when coupled with gallium lung scanning or such blood assays as ACE or immune complexes. However, it is prudent to continue to classify and monitor these lung diseases in patients with broad criteria, and continue to seek additional ones, rather than to restrict them as is the recent trend. Disease activity is not likely to be reflected by one immunologic finding, such as a percentage of a certain subtype of lymphocyte in sarcoidosis, certainly not in all patients. Further correlations between lung tissue histology and lung lavage cells are still needed, until the precision with which lavage actually samples intramural alveolitis is established. It may be necessary to resubmit some patients to open lung biopsy to look again at the tissue-lavage correlations, but only after some new techniques are established. The ethical considerations of, for example, obtaining adequate sized samples of sarcoid lung tissue with thoracotomy may need re-evaluation in the face of the proliferating use and dependence on lavage analysis, which does not have enough tissue histology-cellular cytology correlation at present. First, new techniques need to be developed involving microdissection and ultrastructural cell analysis which can be perfected and verified in animal models in which other forms of granulomatous lung disease may suffice for study. Much of this article has examined the comparison between air-space cells and parenchyma, since analysis of lung lavage fluid constituents is being used for diagnosis, for classifying or staging interstitial disease activity, and for monitoring the evolution of disease. It is apparent that very few human studies have been addressed to this particular correlation. Of those available it is difficult to judge how meaningful these kind of compartmental cell analyses are, given so many possible variables in sampling techniques. Lung lavage does not provide a quantitative recovery of alveolar space cells, and in the case of PMNs retrieved from normal rabbit lungs, lavage may recover less than 50 percent of the observed PMNs. A two-week interval between lavage and lung biopsy is sufficient time for any cells that were removed to repopulate the air spaces, so that an extraction cell method is removing air space as well as interstitial and perhaps vascular located cells. Lung tissue is quite difficult to disperse into single cell preparations even with drastic forms of enzyme digestion; yet the efficiency of the extration procedures are not discussed thoroughly. Teasing apart tissue or agitating cells out of tissue fragments probably do not give quantitative yields. Moreover, lymphocytes seem to withstand tissue disruption the best, either because they are more durable than inflammatory cells or because they do not adhere and stick to tissue as well as PMNs and are shelled out more easily. Finally, extraction methods do not sample any discrete anatomic relationships, and various in situ arrangements between contiguous areas of inflammation or or within diseased alveolar units (mural and luminal alveolar infiltrating cells) are not preserved. Some reappraisal is in order.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalSeminars in Respiratory Medicine
Issue number1
StatePublished - 1984

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine


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