Chest
Volume 106, Issue 4, October 1994, Pages 1116-1123
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Clinical Investigations: Inflammatory Airways
Erythromycin Inhibits Neutrophil Chemotaxis in Bronchoalveoli of Diffuse Panbronchiolitis

https://doi.org/10.1378/chest.106.4.1116Get rights and content

The efficacy of low dose long-term erythromycin (EM) therapy in the treatment of chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB), has been reported, but its therapeutic mechanism is still unclear. In 13 patients receiving oral EM therapy the accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly reduced (p<0.05), this reduction corresponds with an improvement in clinical symptoms. We sought to determine whether neutrophil chemotactic activity (NCA) in lavage fluid obtained from these 13 patients with DPB would respond to EM therapy. Pretreatment NCA in all patients was significantly elevated compared with levels in normal healthy nonsmoking volunteers (p<0.001), and the level was greatly reduced after EM therapy (p<0.001). In addition, this reduction correlated with increased percentages of neutrophils in the BAL fluid (r=0.737, p<0.01). Gel-filtration chromatography was also performed to characterize chemotactic factors. Pre-EM treatment BAL fluid revealed four NCA peaks (about molecular weight 15, 000, 8, 000, 1, 500, and 300 daltons) in the elution profile, and chemotactic activity was reduced in all areas after EM therapy. These findings indicate that NCA in lavage fluid from patients with DPB consists of various components. Although it was not clear which component is predominantly affected, these results indicate that EM may inhibit the migration of neutrophils to inflammatory sites by reducing the intrapulmonary chemotactic gradient, thus, ultimately reducing pulmonary inflammation.

Section snippets

Patient Population

We evaluated neutrophil chemotactic activity (NCA) in 13 patients with DPB (10 men and 3 women; mean age 39.2Ā±4.9 years) who satisfied the diagnostic criteria for DPB set out by the Japanese Ministry of Health and Welfare. All the patients had the following clinical features: (1) symptoms of chronic cough with sputum production and exertional dyspnea, (2) physical signs of coarse crackles and rhonchi, (3) typical radiologic features on chest roentgenogram of diffuse nodular shadows and

Clinical Characteristics of Patients

Neutrophil chemotactic activity was measured in the pre- and post-EM treatment BAL fluid of the 13 DPB patients. As shown in Table 1, their mean duration of disease was 9.0Ā±1.9 years; the onset was insidious. Sputum cultures at the time of admission yielded Hemophilus influenzae in four patients (cases 6, 8, 10, and 11), Pseudomonas aeruginosa in three (cases 4, 9, and 13), Staphylococcus aureus in one (case 1), and normal flora in 5 (cases 2, 3, 5, 7, and 12). Erythromycin was administered to

Discussion

Diffuse panbronchiolitis is a chronic inflammatory disease that is manifested in a diffuse fashion in both lungs in the region of the respiratory bronchioles. Typical features of the lesions are thickening of the walls of the bronchioles, with infiltration of lymphocytes, plasma cells, and histiocytes; proliferation of lymphfollicles; accumulation of foamy cells within the wall and neighboring area; and extension of these inflammatory changes toward the peribronchiolar tissues.1, 2

The treatment

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