Chest
Volume 119, Issue 4, April 2001, Pages 1131-1137
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Clinical Investigations: Antibiotics
Plasma and BAL Fluid Concentrations of Antimicrobial Peptides in Patients With Mycobacterium avium- intracellulare Infection

https://doi.org/10.1378/chest.119.4.1131Get rights and content

Study objectives

To investigate the roles of human°° -defensin (HAD), human ββ-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with Mycobacterium avium-intracellulare infection (MAI).

Patients

The study included 25 patients (10 men) with MAI who visited our hospital between June 1998 and August 1999.

Measurements and results

In patients with pulmonary MAI, we measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by radioimmunoassay. Plasma concentrations of HAD and HBD-2 in those patients were higher than those in control subjects, whereas HBD-1 levels were similar to those in the control subjects. High levels of HAD and HBD-2, but not HBD-1, also were observed in the BALF of MAI patients. There was a positive correlation between HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI. BALF HBD-2 concentrations also correlated positively with those of plasma HBD-2 and BALF IL-1ββ in MAI patients. Patients with cavity formation on the chest roentgenogram had higher HAD and HBD-2 levels in their BALF than those of patients without cavity formation. Treatment with clarithromycin combined with two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD-2 concentrations in responders, but not in nonresponders.

Conclusion

Our findings suggest that HAD and HBD-2 may participate in host defense and local remodeling of the respiratory tract in patients with MAI and that plasma HBD-2 levels may be a useful marker of disease activity in patients with pulmonary MAI.

Section snippets

ample Preparation

We studied 25 consecutive patients with MAI who visited our hospital between June 1998 and August 1999. The group consisted of 15 women and 10 men with a mean (± SEM) age of 60.9 ± 3.5 years and included 3 smokers, 2 ex-smokers, and 20 nonsmokers. MAI was diagnosed and treated according to the guidelines set by the American Thoracic Society.16 The patients were deemed to be free of other lung diseases based on the following findings: (1) negative history; (2) normal findings on a chest

Patients Characteristics

The main symptoms were cough (15 patients), sputum production (10 patients), and hemoptysis (6 patients). The chest CT scans revealed small nodules in all patients, ectasia of peripheral bronchi and/or bronchioles in 11 patients, and cavity formation in 10 patients. Seventeen of 25 MAI patients successfully responded to therapy, while the remaining 8 patients were nonresponders.

Laboratory Data and BALF Findings

The Gaffky scale number in MAI patients ranged from 0 to 6 (mean, 3). The mean values and ranges for erythrocyte

Discussion

The major finding of the present study was that MAI patients, especially those with cavity formation and/or bronchiectasis, showed high concentrations of HAD and HBD-2 both in plasma and BALF. HAD in neutrophils plays an important role in host defense against pathogens. However, once HAD is released from the neutrophils, it participates in lung injury, as observed in their cytotoxic effects in neutrophil-mediated pulmonary diseases such as diffuse panbronchiolitis,15 cystic fibrosis,21 and ARDS.

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