ABSTRACT
Because 75% of deaths attributable to sarcoidosis occur due to progressive respiratory
failure, the staging of pulmonary disease and the accurate identification of changes
in disease severity with time are both an essential part of clinical management. Historically,
pulmonary function tests (PFTs) and chest radiographic appearances have been applied
to both goals. Several additional investigations have been proposed as markers of
active disease, including gallium scanning, positron emission tomographic (PET) scanning,
high-resolution computed tomographic (HRCT) scanning, bronchoalveolar lavage, and
candidate biomarkers such as serum angiotensin-converting enzyme (ACE) levels and
serum interleukin (IL)-2 receptor levels. However, none of these tests has been shown
to add value to PFTs and chest radiography, either in staging disease at baseline
or in detecting change, although PET scanning merits further evaluation with particular
reference to the suppression of activity with treatment in irreversible disease. Furthermore,
no single pulmonary function or chest radiographic variable in isolation is accurate
in all cases in this heterogeneous disease. Thus the evaluation of pulmonary disease
in sarcoidosis is a multidisciplinary exercise, with the integration of PFTs (including
measures of gas transfer) and chest radiographic findings (best assessed using simple
user-friendly grading systems) with symptomatic severity and change.
KEYWORDS
Pulmonary sarcoidosis - staging of disease severity - identification of change
REFERENCES
- 1
Turner-Warwick M, McAllister W, Lawrence R, Britten A, Haslam P L.
Corticosteroid treatment in pulmonary sarcoidosis: do serial lavage lymphocyte counts,
serum angiotensin converting enzyme measurements, and gallium-67 scans help management?.
Thorax.
1986;
41
903-913
- 2
Keogh B A, Crystal R G.
Clinical significance of pulmonary function tests. Pulmonary function testing in interstitial
pulmonary disease. What does it tell us?.
Chest.
1980;
78
856-865
- 3
Neville E, Walker A, James D G.
Prognostic factors predicting outcome of sarcoidosis: an analysis of 818 patients.
Q J Med.
1983;
52
525-533
- 4
Rømer F K.
Presentation of sarcoidosis and outcome of pulmonary changes.
Dan Med Bull.
1982;
29
27-32
- 5
Alhamad E H, Lynch III J P, Martinez F J.
Pulmonary function tests in interstitial lung disease: what role do they have?.
Clin Chest Med.
2001;
22
715-750
ix
- 6
Harrison B D, Shaylor J M, Stokes T C, Wilkes A R.
Airflow limitation in sarcoidosis—a study of pulmonary function in 107 patients with
newly diagnosed disease.
Respir Med.
1991;
85
59-64
- 7
Lynch III J P, Kazerooni E A, Gay S E.
Pulmonary sarcoidosis.
Clin Chest Med.
1997;
18
755-785
- 8
Gleeson F V, Traill Z C, Hansell D M.
Evidence of expiratory CT scans of small-airway obstruction in sarcoidosis.
AJR Am J Roentgenol.
1996;
166
1052-1054
- 9
Hansell D M, Milne D G, Wilsher M L, Wells A U.
Pulmonary sarcoidosis: morphologic associations of airflow obstruction at thin section
CT.
Radiology.
1998;
209
697-704
- 10
Chambellan A, Turbie P, Nunes H, Brauner M, Battesti J P, Valeyre D.
Endoluminal stenosis of proximal bronchi in sarcoidosis: bronchoscopy, function, and
evolution.
Chest.
2005;
127
472-481
- 11
Carrington C B.
Structure and function in sarcoidosis.
Ann N Y Acad Sci.
1976;
278
265-283
- 12
Levinson R S, Metzger L F, Stanley N N et al..
Airway function in sarcoidosis.
Am J Med.
1977;
62
51-59
- 13
Shorr A F, Davies D B, Nathan S D.
Predicting mortality in patients with sarcoidosis awaiting lung transplantation.
Chest.
2003;
124
922-928
- 14
Baughman R P, Engel P J, Meyer C A, Barrett A B, Lower E E.
Pulmonary hypertension in sarcoidosis.
Sarcoidosis Vasc Diffuse Lung Dis.
2006;
23
108-116
- 15
Scadding J G.
Prognosis of intrathoracic sarcoidosis in England.
BMJ.
1961;
2
1165-1172
- 16
Israel H L, Lenchner G, Steiner R M.
Late development of mediastinal calcification in sarcoidosis.
Am Rev Respir Dis.
1981;
124
302-305
- 17
Gawne-Cain M L, Hansell D M.
The pattern and distribution of calcified mediastinal lymph nodes in sarcoidosis and
tuberculosis: a CT study.
Clin Radiol.
1996;
51
263-267
- 18
Smellie H, Hoyle C.
The natural history of pulmonary sarcoidosis.
Q J Med.
1960;
29
539-558
- 19
Ellis K, Renthal G.
Pulmonary sarcoidosis. Roentgenographic observations on course of disease.
AJR Am J Roentgenol.
1962;
88
1070-1083
- 20
Costabel U, Guzman J.
Bronchoalveolar lavage in interstitial lung disease.
Curr Opin Pulm Med.
2001;
7
255-261
- 21
Remy-Jardin M, Giraud F, Remy J, Wattinne L, Wallaert B, Duhamel A.
Pulmonary sarcoidosis: role of CT in the evaluation of disease activity and functional
impairment and in prognosis assessment.
Radiology.
1994;
191
675-680
- 22 Hansell D M, Armstrong P, Lynch D A, McAdams H P. Imaging of Diseases of the Chest.
4th ed. Philadelphia; Elsevier Mosby 2005: 635-636
- 23
Drent M, De Vries J, Lenters M et al..
Sarcoidosis: assessment of disease severity using HRCT.
Eur Radiol.
2003;
13
2462-2471
- 24
Oberstein A, von Zitzewitz H, Schweden F, Müller-Quernheim J.
Non invasive evaluation of the inflammatory activity in sarcoidosis with high-resolution
computed tomography.
Sarcoidosis Vasc Diffuse Lung Dis.
1997;
14
65-72
- 25
Köhn H, Klech H, Mostbeck A, Kummer F.
67Ga scanning for assessment of disease activity and therapy decisions in pulmonary
sarcoidosis in comparison to chest radiography, serum ACE and blood T-lymphocytes.
Eur J Nucl Med.
1982;
7
413-416
- 26
Nishiyama Y, Yamamoto Y, Fukunaga K et al..
Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis.
J Nucl Med.
2006;
47
1571-1576
- 27
Braun J J, Kessler R, Constantinesco A, Imperiale A.
18F-FDG PET/CT in sarcoidosis management: review and report of 20 cases.
Eur J Nucl Med Mol Imaging.
2008;
35
1537-1543
- 28
Teirstein A S, Machac J, Almeida O, Lu P, Padilla M L, Iannuzzi M C.
Results of 188 whole-body fluorodeoxyglucose positron emission tomography scans in
137 patients with sarcoidosis.
Chest.
2007;
132
1949-1953
- 29
Keijsers R GM, Verzijlbergen J F, van Diepen D M, van den Bosch J MM, Grutters J C.
18F-FDG PET in sarcoidosis: an observational study in 12 patients treated with infliximab.
Sarcoidosis Vasc Diffuse Lung Dis.
2008;
25
143-149
- 30
Ziegenhagen M W, Rothe M E, Schlaak M, Müller-Quernheim J.
Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis.
Eur Respir J.
2003;
21
407-413
- 31
Drent M, Jacobs J A, de Vries J, Lamers R JS, Liem I H, Wouters E FM.
Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?.
Eur Respir J.
1999;
13
1338-1344
- 32
Shorr A F, Torrington K G, Parker J M.
Serum angiotensin converting enzyme does not correlate with radiographic stage at
initial diagnosis of sarcoidosis.
Respir Med.
1997;
91
399-401
- 33
Leung A N, Brauner M W, Caillat-Vigneron N, Valeyre D, Grenier P.
Sarcoidosis activity: correlation of HRCT findings with those of 67Ga scanning, bronchoalveolar
lavage, and serum angiotensin-converting enzyme assay.
J Comput Assist Tomogr.
1998;
22
229-234
- 34
Stokes G S, Monaghan J C, Schrader A P, Glenn C L, Ryan M, Morris B J.
Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic
tests for serum ACE activity.
Aust N Z J Med.
1999;
29
315-318
- 35
Bradley B, Branley H M, Egan J J British Thoracic Society Interstitial Lung Disease
Guideline Group, British Thoracic Society Standards of Care Committee et al.
Interstitial lung disease guideline: the British Thoracic Society in collaboration
with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society.
Thorax.
2008;
63(Suppl 5)
v1-v58
- 36
Ziegenhagen M W, Benner U K, Zissel G, Zabel P, Schlaak M, Müller-Quernheim J.
Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R
are prognostic markers.
Am J Respir Crit Care Med.
1997;
156
1586-1592
- 37
Keicho N, Kitamura K, Takaku F, Yotsumoto H.
Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of
disease activity in sarcoidosis.
Chest.
1990;
98
1125-1129
- 38
Grutters J C, Fellrath J M, Mulder L, Janssen R, van den Bosch J M, van Velzen-Blad H.
Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical
evaluation.
Chest.
2003;
124
186-195
- 39
Müller-Quernheim J, Pfeifer S, Strausz J, Ferlinz R.
Correlation of clinical and immunologic parameters of the inflammatory activity of
pulmonary sarcoidosis.
Am Rev Respir Dis.
1991;
144
1322-1329
- 40 ILO Guidelines for the Use of ILO International Classification of Radiographs of
Pneumoconioses. Geneva; International Labor Office 1980 Occupational Safety Series
No. 22
- 41
Judson M A, Gilbert G E, Rodgers J K, Greer C F, Schabel S I.
The utility of the chest radiograph in diagnosing exacerbations of pulmonary sarcoidosis.
Respirology.
2008;
13
97-102
- 42
Gibson G J, Prescott R J, Muers M F et al.
British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment.
Thorax.
1996;
51
238-247
- 43
Muers M F, Middleton W G, Gibson G J et al..
A simple radiographic scoring method for monitoring pulmonary sarcoidosis: relations
between radiographic scores, dyspnoea grade and respiratory function in the British
Thoracic Society Study of Long-Term Corticosteroid Treatment.
Sarcoidosis Vasc Diffuse Lung Dis.
1997;
14
46-56
- 44
Baughman R P, Shipley R, Desai S Sarcoidosis Investigators et al.
Changes in chest roentgenogram of sarcoidosis patients during a clinical trial of
infliximab therapy: comparison of different methods of evaluation.
Chest.
2009;
136
526-535
- 45
American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis
and Other Granulomatous Disorders .
Statement on Sarcoidosis.
Am J Respir Crit Care Med.
1999;
160
736-755
Athol U WellsM.D.
Interstitial Lung Disease Unit, Royal Brompton Hospital, Emmanuel Kaye Bldg., Manresa
Rd., Chelsea, London
SW3 6LR UK
eMail: A.wells@rbh.nthames.nhs.uk