Elsevier

Clinics in Chest Medicine

Volume 18, Issue 4, 1 December 1997, Pages 787-797
Clinics in Chest Medicine

BRONCHOALVEOLAR LAVAGE: Still Useful in Diagnosing Sarcoidosis?

https://doi.org/10.1016/S0272-5231(05)70418-4Get rights and content

Sarcoidosis is a systemic inflammatory disease of unknown cause. Pathophysiologically, a hyperimmune response to unknown antigens can be found at the lesion sites. In lungs, activated macrophages and T cells are characterized as macrophage–T lymphocyte alveolitis, which precedes epithelioid cell granuloma formation (Fig. 1). The granulomas may regress spontaneously or may persist and develop into fibrosis. The factors determining the evolution of granulomas remain unclear.15, 16, 17, 34, 40, 43

The clinical manifestations of sarcoidosis are various, and the involvement of one organ does not always parallel that of other organs during the clinical course. Conceptually, a typical evolution from bilateral hilar shadow (BHL) to parenchymal lesions is likely to take place in the majority of patients with pulmonary sarcoidosis.41

Clinical courses of sarcoidosis seem to vary in different populations,9, 12, 19, 27 modes of onset, and involved organs.20, 21, 31 The majority of patients with thoracic involvement show spontaneous regression but, in some patients, the lesions persist and develop into pulmonary fibrosis with functional deterioration.

In recent World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) meetings (Kyoto, 1991 and Los Angeles, 1993), some useful consensus summaries were presented. The 1991 definition of sarcoidosis characterizes the disease in considerable detail49:

Sarcoidosis is a multisystem disorder of unknown cause(s). It commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, ocular and skin lesions. Liver, spleen, lymph nodes, salivary glands, heart, nervous system, muscles, bone and other organs may also be involved.

The diagnosis is established when clinico-radiological findings are supported by histological evidence of noncaseating epithelioid cell granulomas. Granulomas of known causes and local sarcoid reactions must be excluded.

Frequently observed immunological features are depression of cutaneous delayed-type hypersensitivity and increased helper cell (CD4)/suppressor cell (CD8) ratio at the site of involvement. Circulating immune complexes along with the signs of B-cell hyperactivity may also be detectable. Other markers of the diseases include elevated levels of serum ACE, increased uptake of radioactive gallium, abnormal calcium metabolism and abnormal fluorescein angiography. Kveim-Siltzbach test, when appropriate cell suspensions are available, may be of diagnostic help.

The course and prognosis may correlate with the mode of onset and extent of the disease. An acute onset with erythema nodosum or asymptomatic bilateral hilar lymphadenopathy usually heralds a self-limiting course, whereas an insidious onset, especially with multiple extra-pulmonary lesions, may be followed by relentless, progressive fibrosis of the lungs and other organs. Corticosteroids relieve symptoms, suppress the formation of granulomas and normalize the SACE levels and the gallium uptake.

Diagnosis of sarcoidosis is fundamentally based on detection of epithelioid cell granuloma in biopsy specimens obtained from the lesion sites, such as lungs, skin, and kidney.18 For a correct diagnosis of sarcoidosis, it is critical to exclude other possibilities, both histologically and clinically. Pulmonary tuberculosis, cryptococcosis, chronic berylliosis, chronic hypersensitivity pneumonitis, and lymphoproliferative diseases are candidates for differentiation.18 In diagnosing thoracic lesions, the presence of extrathoracic lesions supports a diagnosis of pulmonary sarcoidosis. Inversely, it is difficult to diagnose ocular lesions of sarcoidosis without the presence of other tissue involvement.42

In addition, the disease activity may vary at the time of initial examination. It is difficult to diagnose sarcoidosis when it is in an inactive stage, irrespective of treatment. When all those factors are considered, there are clearly many problems before the diagnosis of sarcoidosis can be accurately established.

In light of the circumstances and difficulties just described, the role of bronchoalveolar lavage (BAL) has to be considered with respect to diagnosis.

Section snippets

USEFULNESS OF BRONCHOALVEOLAR LAVAGE IN DISCRIMINATING DISEASE PRESENTATION

Because combined information about cell recovery, cell differentials, and the ratio of CD4 to CD8 T cells can be obtained from the BAL procedure and BAL fluid cells (BALF cells) are considered to reflect pathophysiologic processes in the lungs of patients with diffuse interstitial lung diseases such as sarcoidosis, BAL could offer useful clues for differential diagnosis.16, 36

Although it is impossible to detect a specific cell such as epithelioid cells using BAL, a characteristic finding of

BALF CELL PATTERNS AND DIFFERENTIAL DIAGNOSIS

Based on our experience, performing BAL procedures on 400 healthy subjects and 1600 cases with diffuse interstitial lung diseases, BALF cell findings can be divided into four patterns—healthy pattern, sarcoidosis pattern, bronchiolitis obliterans with organizing pneumonia (BOOP) pattern, and usual interstitial pneumonia (UIP) pattern.

FACTORS THAT AFFECT ACCURACY OF DIAGNOSIS

Factors that affect accuracy of diagnosis in patients with sarcoidosis can be summarized as follows:

  • 1

    Disease activity is one of the critical factors. The majority of patients with pulmonary sarcoidosis are asymptomatic, especially when lesions such as BHL are detected by mass survey. In that condition, various levels of disease activity can be found by BAL at the time of initial examination. Overall clinical evaluation and the use of biopsy to obtain a definite hallmark of granuloma are

DIFFERENTIAL DIAGNOSIS BETWEEN SARCOIDOSIS AND OTHER INTERSTITIAL LUNG DISEASES

Sarcoidosis is a systemic immune-mediated disease and its mode of onset is chronic and insidious except in cases with febrile onset or erythema nodosum. Without typical BHL and cutaneous manifestations, it occasionally is difficult to diagnose sarcoidosis correctly. Especially when only parenchymal interstitial shadows are seen on chest radiograph at the time of initial examination, we are concerned about making a diagnosis. Other additional findings such as elevated serum ACE activity are not

DIAGNOSTIC VALUE OF BALF CELL FINDINGS WITH REGARD TO DISEASE ACTIVITY AND PROGNOSIS

How to determine the disease activity or prognostic factors in patients with sarcoidosis has long been a matter of controversy. The current consensus of the disease activity was proposed as a result of the WASOG meeting in Los Angeles in 1993. Disease activity is considered to be as follows6:

Activity means that something is still acting or working, is causing motion or change, is still evolving, has not come to rest. In sarcoidosis, the term activity implies that the disease is undergoing

SUMMARY AND CONCLUSION

BALF parameters, if evaluated as a diagnostic or prognostic tool, should be based on a full understanding of the clinical profiles and course of pulmonary sarcoidosis. The various markers that have been reported so far are unreliable in determining the prognosis, although BALF lymphocytes and CD4/CD8 ratios are still useful for diagnosing sarcoidosis. It is critical to find feasible markers that relate to a change in disease activity and prognosis, because markers of chronicity may be different

ACKNOWLEDGMENT

We would like to thank Om P. Sharma, MD, for reviewing our manuscript and giving useful advice. We thank M. Kitaichi, MD, for diagnosing lung biopsy specimens. We also thank T. Mikuniya, PhD, N. Satake, MD, T. Mio, MD, M. Shigematsu, for helping with BAL procedures. We thank F. Tanioka, MD and M. Yamada for preparing BALF cell specimens and M. Kurozumi for counting BALF cell differentials. We thank Simon Johnson for checking linguistic problems.

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  • Cited by (0)

    Address reprint requests to Sonoko Nagai, MD, Pulmonary Medicine and Clinical Immunology, Chest Disease Research Institute, Kyoto University, Kyoto, Japan

    This work was supported by a Grant-in-Aid for Medical Science Research (No. 06670610) from the Ministry of Education, Japan, and by a Grant from the Smoking Research Foundation in Japan.

    *

    From the Chest Disease Research Institute, Kyoto University, Kyoto, Japan

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