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MISCELLANEOUS |
1 Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Melbourne, Australia
2 Department of Haematology/Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia
3 Intensive Care Unit, Royal Melbourne Hospital
4 Department of Human Physiology, Flinders University, Australia
5 Statistical Centre, Peter MacCallum Cancer Institute, Melbourne, Australia
6 Department of Pulmonary Medicine, University Hospital, Zurich, Switzerland
7 Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan
Correspondence to:
Correspondence to:
Dr J F Seymour, Division of Haematology/Medical Oncology, Peter MacCallum Cancer Institute, St Andrew’s Place, East Melbourne, Victoria 3002, Australia;
jseymour{at}petermac.unimelb.edu.au
ABSTRACT
Background: Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A – a]DO2), vital capacity (VC), and carbon monoxide transfer factor (TLCO), but alternative serological measures have been sought. Granulocyte-macrophage colony stimulating factor (GM-CSF) neutralising autoantibody is found in patients with idiopathic acquired AP. We have investigated the interrelationships between the levels of this antibody and those of surfactant protein (SP)-A and -B, lactate dehydrogenase (LDH), and conventional measures of disease severity, and the capacity of these parameters to predict the response to rhGM-CSF treatment.
Methods: Blood levels of anti-GM-CSF antibodies, SP-A, SP-B, LDH, and [A – a]DO2, VC, and TLCO were measured before rhGM-CSF treatment and every 2 weeks thereafter in 14 patients with AP.
Results: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83%. SP-A was highly correlated with [A – a]DO2, VC, and TLCO (p
0.02), but other markers were not. Only a normal LDH level was predictive of a response to rhGM-CSF treatment (p=0.03). During treatment a correlation between conventional and serological variables within patients was seen only between SP-A and [A – a]DO2 (p=0.054), LDH levels and [A – a]DO2 (p=0.010), and LDH levels and VC (p=0.019).
Conclusions: Of the serological parameters studied, only SP-A and LDH levels were correlated with conventional measures of disease severity, with LDH most accurately reflecting [A – a]DO2 and vital capacity. Only a normal LDH level predicted a higher likelihood of response to treatment with GM-CSF.
Keywords: pulmonary alveolar proteinosis; granulocyte-macrophage colony stimulating factor; surfactant protein A; surfactant protein B; autoantibodies
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