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BAL in the diagnosis of ILD
Athol WellsRoyal Brompton Hospital
London, UK
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Interstitial lung disease guideline: Interstitial lung disease guideline: the British Thoracic Society in the British Thoracic Society in collaboration with the Thoracic collaboration with the Thoracic Society of Australia and New Zealand Society of Australia and New Zealand and the Irish Thoracic Societyand the Irish Thoracic Society
AU Wells, N Hirani on behalf of the British Thoracic Society Guidelines group. Thorax 2008; 63: supplement v.
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BAL, or TBLB, when required, should be performed before the initiation of treatment (D)
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BAL should be BAL should be considered in all considered in all patients with suspected patients with suspected infection or malignancy infection or malignancy and some rare ILDs. In and some rare ILDs. In such cases, BAL may be such cases, BAL may be diagnostic (C).diagnostic (C).
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Which rare diseases?
Alveolar proteinosis
Diffuse alveolar hemorhage
Lipoid proteinosis
Acute eosinophilic pneumonia
(Langerhans cell histiocytosis)
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Diagnosis of LCH
Histology: characteristic light microscopic findings plus histiocytic S100 positivity, CD1a positivity or Birbeck granules on e.m.
BAL: most often non-diagnostic because heavy smokers have more LC and greater S-100 positivity
Furthermore, in more advanced disease, BAL findings are often non-specific
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At this point the difficulties arise!
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Why are there no reliable diagnostic series for BAL?
Problem of defining the real utility of a test
The assumption in study design that the test is used in isolation
But this is almost NEVER the case
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The real value of a diagnostic test is the degree to which it changes diagnostic perception
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“The only utility of a (diagnostic) test is to reduce uncertainty”
EJ PotchenEJ Potchen
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BAL is not required as BAL is not required as a diagnostic tool in a diagnostic tool in patients with clinical patients with clinical features and HRCT features and HRCT appearances typical appearances typical of IPF (C)of IPF (C)
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A BAL neutrophilia is not really diagnostically useful
Across fibrosing diffuse lung diseases, it appears to reflect more extensive fibrotic change
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This first became This first became obvious in obvious in systemic sclerosissystemic sclerosis
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“An alveolitis on BAL”
A neutrophilia or granulocytosis on BAL had predicted decline in four studies
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The BAL dilemma: severity or intrinsic progressiveness?
• Severe disease is more likely to progress
• Does BAL simply reflect severity? If so, HRCT and PFT are more user-friendly!
• Does BAL disclose progressiveness, independently of disease severity?
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0 10 20 30 40 50 60 70 80 90 1000
10
20
30
40
50
60
70
80
90
100BAL neutrophils 4.0
BAL neutrophils > 4.0
p=0.02
time (mths)
Su
rviv
al (
%)
Neutrophilia in 70/148 cases Neutrophilia in 70/148 cases (47%)(47%)
HR = 2.41 [1.24, 4.56]HR = 2.41 [1.24, 4.56]
Effect confined to two year Effect confined to two year mortality on adjustment for mortality on adjustment for severityseverity
Goh NS. Arthritis Rheum 2007; 56:205-212Goh NS. Arthritis Rheum 2007; 56:205-212
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Strange C. Am J Respir Crit Care Med 2008; 177:91-98Strange C. Am J Respir Crit Care Med 2008; 177:91-98
A complementary statement
The study of Goh: long term follow-up but uncontrolled, variable treatment
The placebo-controlled SLS oral cyclophosphamide study: one year of follow-up
BAL neutrophil content did not predict progression in the placebo arm
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In both the Goh and the Strange studies, BAL neutrophil content correlated with disease extent on HRCT
This fits nicely with old data
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Wells A. Am J Respir Crit Care Med 1994; 150:462-468Wells A. Am J Respir Crit Care Med 1994; 150:462-468
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BAL: SSc versus IPF
BAL findings compared
Higher neutrophil content in IPF
However, identical content when severity (using HRCT or PFT) factored in.
Neutrophil content linked simply to disease severity
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Does this stand up diagnostically when idiopathic NSIP and IPF are compared?
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BAL: NSIP vs COP, IPF
NSIP COP IPF Lymph 37.3% 44.4% 7.2% (40.0, 34.4)
Neut 8.0% 6.4% 5.0%
Eos 5.5% 2.2% 3.3%
(n=31) (n=16) (n=64)
Nagai SR et al. Eur Respir J 1998; 12:1010-1019Nagai SR et al. Eur Respir J 1998; 12:1010-1019
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Similar findings in South Korean data
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But NSIP in East Asian studies has prominent elements of organizing pneumonia with HRCT consolidation often present
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In this scenario, IPF is not a likely differential diagnosis.
By contrast, another sub-group of NSIP patients overlap clinical with IPF. BAL differences would be reallyreally useful
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BAL compared between IPF and NSIP with the clinical features of IPF
Veeraraghavan S et al. Eur Respir J 2003; 22:239-Veeraraghavan S et al. Eur Respir J 2003; 22:239-244244
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BAL findings do not positively diagnose IPF
I believe that they remain useful, even when IPF seems very likely, in in excluding HPexcluding HP
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Differential diagnosis for neutrophilia
Significant fibrosis Acute Infection Vasculitis Bronchiectasis Constrictive bronchiolitis
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In patients for whom the In patients for whom the diagnosis is uncertain after diagnosis is uncertain after clinical assessment and HRCT clinical assessment and HRCT scanning, typical BAL cellular scanning, typical BAL cellular profiles may allow a diagnosis profiles may allow a diagnosis of hypersensitivity of hypersensitivity pneumonitis or sarcoidosis to pneumonitis or sarcoidosis to be made with greater be made with greater confidence confidence (C)(C)
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BTS guidelines translated
BAL is incredibly useful when HP is suspected (and in a number of cases of unsuspected HP)
It often stimulates the performance of biopsy and is therefore, often, indirectly diagnostic
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Differential of a BAL lymphocytosis
Granulomatous disease (HP, sarcoidosis)
COP, COP/NSIP overlap, cellular NSIP
LIP Drug reactions Connective tissue disease
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HP versus sarcoidosis
Striking lymphocytosis favours HP
In theory, CD4/CD8 ratios should discriminate
In practice, there are simply too many exceptions but personal diagnostic algorithms should be respected
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Conclusion
Single greatest utility is in suspected HP amd sarcoidosis
Helps to exclude infection and to diagnose rare disorders
Remarkable lack of hard data post CT