BAL in the diagnosis of ILD Athol Wells Royal Brompton Hospital London, UK

Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and 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 considered in all patients with suspected infection or malignancy and some rare ILDs. In such cases, BAL may be 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 Potchen

BAL is not required as a diagnostic tool in patients with clinical features and HRCT appearances typical 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 obvious in systemic 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?

Neutrophilia in 70/148 cases (47%) HR = 2.41 [1.24, 4.56] Effect confined to two year mortality on adjustment for severity Goh NS. Arthritis Rheum 2007; 56:

Strange 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:

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:

Similar findings in South Korean data

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

really 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 really useful

BAL compared between IPF and NSIP with the clinical features of IPF Veeraraghavan S et al. Eur Respir J 2003; 22:

BAL findings do not positively diagnose IPF in excluding HP I believe that they remain useful, even when IPF seems very likely, in excluding HP

Differential diagnosis for neutrophilia  Significant fibrosis  Acute Infection  Vasculitis  Bronchiectasis  Constrictive bronchiolitis

In patients for whom the diagnosis is uncertain after clinical assessment and HRCT scanning, typical BAL cellular profiles may allow a diagnosis of hypersensitivity pneumonitis or sarcoidosis to be made with greater confidence (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