Association of 
1-antichymotrypsin deficiency with
milder lung disease in patients with cystic fibrosis
R Mahadevaa, L Sharplesb, R I Ross-Russellc, A K Webbd, D Biltone, D A Lomasa
a Respiratory Medicine
Unit, Department of Medicine and Department of Haematology, University
of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in
Disease, Cambridge Institute for Medical Research, Cambridge CB2
2XY, UK, b MRC
Biostatistics Unit, Forvie Site, Cambridge, UK, c Department of Paediatrics, Addenbrooke's
Hospital, Cambridge, UK, d The
Bradbury Cystic Fibrosis Unit, Wythenshawe Hospital, Manchester, UK, e Cystic Fibrosis Unit, Papworth
Hospital, Papworth Everard, Cambridge, UK
Correspondence to: Dr R Mahadeva rm232{at}cam.ac.uk
Received 17 April 2000; Returned to authors 16 June 2000; Revised version received 28 July 2000; Accepted for publication 8 September 2000
BACKGROUND
Cystic
fibrosis (CF) is characterised by an excess of free proteinases that
destroy lung tissue. Despite this, previous studies have shown that
patients with CF with a mild deficiency variant of the proteinase
inhibitor 
1-antitrypsin have less, rather than more,
severe pulmonary disease. Alpha1-antichymotrypsin is
another important serine proteinase inhibitor that protects the lung
against proteolytic attack, and point mutations in the
1-antichymotrypsin gene that result in plasma deficiency
are associated with chronic obstructive pulmonary disease.
METHODSThe
effect of 1-antichymotrypsin deficiency and the -15
1-antichymotrypsin signal peptide genotype on lung
function was assessed in patients with CF.
RESULTSOne
hundred and fifty seven patients with CF were screened and 10 were
identified with a plasma deficiency of
1-antichymotrypsin (plasma concentration <0.2 g/l). In
a multivariate analysis these individuals had significantly less severe
lung disease than those who had normal or raised levels of
1-antichymotrypsin: forced expiratory volume in one
second (FEV1) 69.9% predicted versus 53.2% predicted
(p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for
those with and without 1-antichymotrypsin
deficiency, respectively. The -15 signal peptide genotype did not
affect plasma levels, but the -15 Ala/Ala signal peptide genotype was
over-represented in individuals with CF compared with healthy blood
donor controls.
CONCLUSIONThese
data indicate that deficiency of 1-antichymotrypsin is
associated with less severe pulmonary disease in patients with CF, and
support our previous observations that mild genetic deficiency of a
proteinase inhibitor is associated with an improved outcome.
Keywords: cystic fibrosis;
1-antichymotrypsin;
1-antitrypsin
© 2001 by Thorax
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