Diffuse panbronchiolitis (DPB) is characterized by chronic inflammation, localized predominantly in the respiratory bronchioles, with infiltration of inflammatory cells, such as mononuclear and plasma cells. A high number of neutrophils and activated T lymphocytes are present in the airspaces, and accumulation of the former group has been implicated in the pathogenesis of DPB.
Recent advances in molecular and cellular immunology have shown that a number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation. Neutrophils migrate from the circulation into the inflamed tissue through a series of processes that allow their attachment in the initial stage to the endothelial wall followed by a firm adhesion. The selectin family of adhesion molecules and their respective ligands are important in the early transient adhesion “rolling” phase. The selectin family consists of three distinct carbohydrate receptors expressed by leukocytes (L-selectin), endothelial cells (E-selectin), or platelets and endothelium (P-selectin). Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin supergene family. ICAM-1 acts as a ligand for the (32 leukocyte integrins, such as lymphocyte function-associated antigen-1 and Mac-1, while VCAM-1 binds the very late antigen-4, one of the integrins. Integrin adhesion to ICAM-1 or VCAM-1 is thought to stabilize the adhesion of leukocytes to the endothelium. Recent studies have identified the soluble forms of these adhesion molecules in the serum and BAL fluid (BALF) of healthy subjects and patients with malignancy or inflammatory lung diseases. It is likely that these soluble adhesion molecules originate from adhesion molecules expressed on activated cells, and that their presence in the peripheral circulation may reflect inflammatory activity. www.mycanadianpharmacy.com
In the present study, we measured the serum levels of soluble adhesion molecules in DPB patients to determine whether they reflect disease activity.
Materials and Methods
The study population consisted of two groups of patients with chronic neutrophil-mediated airway inflammation, including 27 patients with DPB (13 female and 14 male), 13 patients with bronchiectasis (9 female and 4 male), and healthy volunteers (control subjects, n=15: 8 female and 7 male). Healthy volunteers (aged 31 ±11 years) were younger than patients with DPB (48±16 years) and bronchiectasis (60±14 years). At the time of the investigation, one patient with bronchiectasis and one volunteer were smokers. The diagnosis of DPB was based on the new criteria published by the Japanese Ministry of Health and Welfare in 1995. These criteria included the following: productive cough and dyspnea on exertion; rales and rhonchi on physical examination; diffuse disseminated fine nodular shadows, mainly in the lower lung fields on chest radiograph or CT; the two abnormalities of FEV1 <70% and Pa02 <80 mm Hg; cold hemagglutination >64; and the presence or history of chronic sinusitis. Nine DPB patients had their conditions diagnosed histopathologically by open lung biopsy specimens. The serum levels of the soluble adhesion molecules were also measured in 19 of 27 DPB patients after approximately 6 months of continuous treatment with macrolide antibiotics. Eight of these patients were treated with 600 mg/d erythromycin, four with 150 mg/d roxithromycin, and seven with 200 mg/d clarithromycin.- None received other antibiotics or corticosteroids during the course of the study. All patients with bronchiectasis reported having cough and sputum for >2 years, and were differentiated from DPB by the presence of bronchiectatic changes with no fine nodular shadows on the chest radiograph or CT scans. BAL was performed in all DPB patients, 10 of 13 patients with bronchiectasis, and 11 healthy volunteers. The percent vital capacity (VC%) (DPB, 83±18; bronchiectasis, 87±22%) and the percent predicted FEVX (DPB, 68±13%; bronchiectasis, 71 ±12%) were not different. However, Pa02 in patients with bronchiectasis (79±12 mm Hg) was higher than in patients with DPB (71 ±9 mm Hg, p<0.05).