BAL in the diagnosis of ILD

Athol WellsRoyal Brompton Hospital

London, UK

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.

BAL, or TBLB, when required, should be performed before the initiation of treatment (D)

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).

Which rare diseases?

Alveolar proteinosis

Diffuse alveolar hemorhage

Lipoid proteinosis

Acute eosinophilic pneumonia

(Langerhans cell histiocytosis)

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

At this point the difficulties arise!

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

The real value of a diagnostic test is the degree to which it changes diagnostic perception

“The only utility of a (diagnostic) test is to reduce uncertainty”

EJ PotchenEJ Potchen

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)

A BAL neutrophilia is not really diagnostically useful

Across fibrosing diffuse lung diseases, it appears to reflect more extensive fibrotic change

This first became This first became obvious in obvious in systemic sclerosissystemic sclerosis

“An alveolitis on BAL”

A neutrophilia or granulocytosis on BAL had predicted decline in four studies

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?

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

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

In both the Goh and the Strange studies, BAL neutrophil content correlated with disease extent on HRCT

This fits nicely with old data

Wells A. Am J Respir Crit Care Med 1994; 150:462-468Wells A. Am J Respir Crit Care Med 1994; 150:462-468

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

Does this stand up diagnostically when idiopathic NSIP and IPF are compared?

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

Similar findings in South Korean data

But NSIP in East Asian studies has prominent elements of organizing pneumonia with HRCT consolidation often present

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

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

BAL findings do not positively diagnose IPF

I believe that they remain useful, even when IPF seems very likely, in in excluding HPexcluding HP

Differential diagnosis for neutrophilia

Significant fibrosis Acute Infection Vasculitis Bronchiectasis Constrictive bronchiolitis

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)

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

Differential of a BAL lymphocytosis

Granulomatous disease (HP, sarcoidosis)

COP, COP/NSIP overlap, cellular NSIP

LIP Drug reactions Connective tissue disease

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

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