There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma.With the aid of image analysis, the fractional areas of total collagen and elastic fibres were quantified within the ASM of 35 subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA) patients and 22 nonasthmatic control cases. Expression of collagen I and III, fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in 22 FA and 10 control cases.In the large airways of FA cases, the fractional area of elastic fibres within the ASM was increased compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large airways of FA cases compared with controls. Elastic fibres were increased in small airways in FA only in comparison with NFA cases.There is altered extracellular matrix composition and a degradative environment within the airway smooth muscle in fatal asthma patients, which may have important consequences for the mechanical and synthetic functions of airway smooth muscle. It has previously been demonstrated that ASM cells exposed to serum from patients with asthma produce increased levels of ECM proteins [6]. In turn, ECM proteins are able to affect the proliferative and secretory state of the ASM [7]. ASM cells secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) [8], which have a role in the immunomodulatory mechanisms regulating ECM composition in asthma patients.In asthma patients, abnormal deposition of ECM elements has been described in the submucosal and adventitial areas of large and small airways [9][10][11][12]. The fractional area of the ECM has also been shown to be increased within the ASM layer in fatal asthma (FA) cases [13], but there are important reasons for better understanding of this subject. First, changes in the ECM composition within the ASM may affect its contractile properties. Digestion with collagenase of the ECM associated with ASM results in increased force generation and shortening in strips of ASM

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