Asthma is characterized by excessive airway narrowing and airway wall inflammation. In cases of fatal asthma, increased thickness of the airway wall is observed and may account for excessive airway narrowing when smooth muscle contracts. This study was undertaken to examine airway dimensions in large and small airways in both fatal and nonfatal cases of asthma. Airway wall areas (total, inner, and outer relative to smooth muscle layer), epithelial integrity, smooth muscle shortening, and the areas of smooth muscle, cartilage, and mucous glands were compared in transverse sections of large and small airways of subjects dying of asthma (fatal asthma, n = 11), those dying suddenly of nonrespiratory diseases and having a definite history of asthma (nonfatal asthma, n = 13), and those dying suddenly without any history of respiratory illness (control, n = 11). Airways were grouped by size using the basement membrane perimeter for comparison. All areas were expressed as areas per millimeter of basement membrane. In cartilaginous airways, the cases of fatal asthma had greater (p < 0.05) total wall, inner wall, outer wall, smooth muscle, mucous gland and cartilage areas than did control and nonfatal cases. The inner wall area was greater in the fatal and nonfatal cases than in the control cases (p < 0.05) in the small cartilaginous airways and membranous bronchioles (MB). In small MB (perimeter < 2 mm), the total and outer wall areas were greater (p < 0.05) in cases of fatal and nonfatal asthma than in control cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D deficiency causes deficits in lung function that are primarily explained by differences in lung volume. This study is the first to provide direct mechanistic evidence linking vitamin D deficiency and lung development, which may explain the association between obstructive lung disease and vitamin D status.

Hypertrophy of ASM cells occurs in the large airways in both nonfatal and fatal cases of asthma, but hyperplasia of ASM cells is present in the large and small airways in fatal asthma cases only. Both are associated with an absolute increase in ECM. Duration of asthma has little or no effect on ASM hypertrophy or hyperplasia or f(ECM).

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

Group B streptococci (GBS) cause invasive disease in neonates, pregnant adults, and nonpregnant adults with underlying or chronic disease. Previous studies found capsular serotypes Ia, Ib, II, and III cause invasive disease. Prospective population-based surveillance of invasive GBS disease was done from June 1992 to June 1993 in metropolitan Atlanta: 279 patients had invasive disease. Of these, 43% were < or = 6 months old, and 57% were adults. The incidence among all adults was 7.7/100,000/year, 33% higher than in 1989-1990 (P < .01). The incidence in nonpregnant adults was 5.9/100,000/year, 37% higher than in 1989-1990 (P < .02). Serotyping of 178 patient isolates revealed that 34% had GBS serotype Ia or Ia/c, 8% had Ib/c, 6% had II or II/c, 29% had III, 0% had IV, 21% had V, and 2% were nontypeable. Serotype V was recovered from all groups and was the most common serotype from nonpregnant adults. Serotype V isolates appeared to be highly related genetically. The increasing incidence of GBS disease in adults, the changing distribution of serotypes, and the emergence of serotype V will impact vaccine strategies.