The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF).
To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies.
Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only.
Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant.
Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary.
"In recent years, there has been increased interest in validating and developing new therapies for patients without cystic fibrosis . These include inhaled antibiotics (tobramycin, aztreonam, ciprofloxacin, colistin, amikacin) , hyperosmolar agents (hypertonic saline solution, dry powder mannitol) [10,11], anti-inflammatory agents (macrolides, corticosteroids) [7,12], bronchodilators (salbutamol) ,chest physiotherapy, physical exercise and nutritional treatment [7,14-16]. In the field of chest physiotherapy several secretion management techniques have been proposed: they include modified postural drainage , assisted cough , active cycle of breathing techniques [17,18], oscillatory positive-expiratory pressure devices [17,18] and intrapulmonary percussive ventilation . "
[Show abstract][Hide abstract] ABSTRACT: High-frequency airway clearance (HFCWC) assist devices generate either positive or negative trans-respiratory pressure excursions to produce high-frequency, small-volume oscillations in the airways.
HFCWC can lead to changes in volume of 15–57 ml and in flow up to 1.6 L/s, which generate minimal coughing to mobilize secretions. The typical treatment lasts 20–30 minutes, and consists of short periods of compression at different frequencies, separated by coughing.
The aim of this study was to find the more efficacious treatment in patients with bronchiectasis: traditional techniques of chest physiotherapy (CPT) versus high frequency oscillation of the chest wall in patients with bronchiectasis.
37 patients were enrolled. Seven of them were excluded. Computer randomization divided the patients into three groups:
– 10 patients treated with HFCWO by using the Vest® Airway Clearance System;
– 10 patients treated with traditional techniques of air way clearance (PEP bottle, PEP mask, ELTGOL, vibratory positive expiratory pressure);
– 10 patients received medical therapy only (control group).
To be eligible for enrollment, participants had to be between 18 and 85 years old and have a diagnosis of bronchiectasis, confirmed on high resolution computed tomography. Exclusion criteria: lack of informed consent, signs of exacerbation, cystic fibrosis. Before the treatment, each patient had blood tests, sputum volume and cell count, pulmonary function tests and on the quality of life inventories (MMRC, CAT, BCSS). The results were processed through the covariance analysis, performed with the R-Project statistical program. It has been considered a positive result p <005.
Both treatments (traditional CPT and HFCWO) showed a significant improvement in some biochemical and functional respiratory tests as well as in the quality of life compared to the control group. The use of HFCWO compared to CPT also produced a significant improvement in blood inflammation parameter C-RP (p ≤0.019), parameters of lung functionality associated with bronchial obstruction (FVC, FEV1) (p ≤0.006 and p ≤0.001), and in the dyspnea. Improvement in quality of life scales was noted. (BCSS, CAT) (both p ≤0.001). No significant changes of total cell counts in sputum samples were observed in the two groups. In the HFCWO group a significant reduction of neutrophils percentage (p≤0.002) and a significant increase of macrophages percentage (p ≤0.012).
The HFCWO technique provides an improvement both in pulmonary function and quality of life related parameters in patients with chronic hypersecretive disease. Since those patients need daily airway clearance, this treatment should be included among the principal options in chest physiotherapy. The study was registered as ChiCTR-TRC-12002134 at http://www.chictr.org.
BMC Pulmonary Medicine 04/2013; 13(1):21. DOI:10.1186/1471-2466-13-21 · 2.40 Impact Factor
"This elevation in the cytokines, coupled with the elevated proteases released from neutrophils, namely, neutrophil elastase, MMP-2, MMP-6, and MMP-9, overwhelms the antiprotease defence mechanisms rendering the lung vulnerable to destruction   . The use of antibiotics has been shown to result in a reduction of these proinflammatory cytokines  "
[Show abstract][Hide abstract] ABSTRACT: Non-cystic fibrosis-related bronchiectasis is a chronic inflammatory lung disease, which is regarded as an "orphan" lung disease, with little research devoted to the study of this condition. Bronchiectasis results in impaired quality of life and mortality if left untreated. The tools available in the armamentarium for the management of bronchiectasis entail antibiotic therapy traditionally used to treat exacerbations, stratagems to improve mucociliary clearance, and avoidance of toxins. Macrolides have been known for the last two decades to have not only anti-bacterial effects but immunomodulatory properties as well. In cystic fibrosis, the use of macrolides is well documented in subjects colonized with Pseudomonas aeruginosa, to improve quality of life and lung function. There is currently emerging evidence to suggest the benefit of macrolides in subjects not colonized with Pseudomonas aeruginosa. This beneficial effect has been less explored in the context of bronchiectasis from other causes. The purpose of this paper is to review the current literature on the use of macrolides in non-cystic fibrosis related bronchiectasis in paediatrics.
Mediators of Inflammation 04/2012; 2012(3):134605. DOI:10.1155/2012/134605 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective. The present study aims at reviewing the main publications on the use of macrolides as immunomodulators in patients with noncystic fibrosis bronchiectasis. Source of Data. The Medline database was our source of data for this research carried out until June 2011, using the key words: macrolides and bronchiectasis, while searching for original articles and reviews. Summary of Data. Seven clinical studies that evaluated the action of the macrolides in patients with bronchiectasis were found. There was the sputum volume, reduction in pulmonary exacerbation frequency, and in the use of antimicrobial treatment, in addition to pulmonary function improvement. Conclusions. Anti-inflammatory action and immunomodulatory effects can be attributed to macrolides when administered in low doses and on the long term. This use has been well established both in diffuse panbronchiolitis and in cystic fibrosis. Evidence indicates possible benefits in bronchiectasis. Future studies are needed, though, to establish the ideal dose and treatment duration and to understand the implications in the generation of microbial resistance.“When patients have bacteria that are resistant to all antibiotics, prescribe erythromycin, leave them on it for a long time, and they will do much better”
Dr. Harry Shwachman, 1950
Pulmonary Medicine 09/2011; 2011(3):751982. DOI:10.1155/2011/751982
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