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These described gross pathological changes with diffuse mucus plugging of the airways,
sloughing of the epithelial lining, an increase in airway smooth muscle and oedema of the
peribronchial tissues. Light microscopy showed mucus plugs, goblet cell hyperplasia and
apparent thickening of bronchial basement membranes with increased smooth muscle. There
was an infiltration of inflammatory cells with a marked increase in eosinophils. The later
paediatric study (Cutz, Levison et al. 1978) also examined the specimens under electron
microscopy. This again demonstrated mucus plugs, which consisted of epithelial, macrophage
and eosinophil cells and cell fragments. A thickened basement membrane appeared to be
composed of collagen deposits and the submucosa was infiltrated by a mixture of
inflammatory cells, predominantly eosinophils. Recent autopsy studies have compared
pathology specimens between patients with fatal asthma, non-fatal asthma and controls
(Koshino, Teshima et al. 1993; Kepley, McFeeley et al. 2001; Chen, Samson et a1.2004).
Significant smooth muscle shortening, increased submucosal gland area, increased mucus
plugging and an increase in basophils was seen in the cases of fatal asthma compared to the
other groups. These contributed to airway wall thickening with smooth muscle hypertrophy
and increased collagen along the basement membrane. Compared to ten controls, 18 adults
who had died of asthma had proteoglycans prominent in the extra cellular matrix creating
most of the basement membrane thickening seen, with differing types of proteoglycans
expressed in the two groups (de Medeiros Matsushita, da silva et al. 2005).
1.6.2 Studies of inflammation using bronchoscopy and biopsy
The use of bronchoscopy was developed initially as a therapeutic measure by Dr Chevalier
Jackson in 1904 (Reynolds 1987), and later became a way of obtaining airway samples. The
flexible fibreoptic bronchoscope was introduced into medical centres in the early 1970s
(Ikeda 1970) with appropriate guidelines (Smiddy, Ruth et al. l97l; Sackner, Wanner er al.
1972)' which were later modified to include standards for bronchoalveolar lavage (BAL)
(Bernstein, Boushey et al. 1985; Reynolds 1987; Turner-Warwick and Haslam l9g7) and
detailed indications and protocols for the procedure were subsequently published (Klech and
Pohl 1989; Kelch and Hutter 1990; Bleecker, McFadden et al. l99Z: Rennard, Aalbers et al.
1998; Haslam and Baughman 1999; Reynolds 2000). The development of paediatric
bronchoscopy commenced a decade later (Wood and Sherman 1980; Wood l9g5) when
construction of smaller bronchoscopes became possible and these entered clinical practice in
the mid 1990s (Perez and Wood 1994; Wood 1996; Rennard, Aalbers er al. 1998; ERS 2000;
Wood 20[l; Midulla, de Blic et aL.2003). Thus these technical advances allowed biopsy and
BAL studies in 'living' patients to be undertaken.
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