A pilot study of low-dose erythromycin in bronchiectasis.
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Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis. (+info)
Degradation of porstaglandin F2alpha in the human pulmonary circulation.
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Degradation of prostaglandins (PGs) during passage through the human pulmonary circulation was investigated by measuring the transpulmonary plasma PGF2 alpha difference during continuous intravenous infusion of PGF2 alpha (5-10 mug/min). Seven patients with cardiological disorders and two patients with extensive pulmonary abnormalities were investigated during diagnostic cardiac catheterization. PGF2 alpha levels were measured by radioimmunoassay. The seven cardiac patients were found to have transpulmonary PGF2 alpha differences of 47-88%, indicating metabolism of the PG in the lungs. A patient with extensive bronchiectasis had an apparently normal transpulmonary PGF2alpha difference despite gross abnormalities in routine lung function tests. A patient with primary pulmonary arterial hypertension showed no metabolism of PGF2alpha in the pulmonary circulation. The results show that PG degradation is an aspect of normal lung function and suggest that it becomes imparied when extensive pulmonary vascular damage exists. (+info)
Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress.
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BACKGROUND: Bronchiectasis is a chronic inflammatory lung disease associated with increased production of oxidants due mostly to neutrophilic inflammation. Induction of heme oxygenase (HO-1) by reactive oxygen species is a general cytoprotective mechanism against oxidative stress. HO-1 catabolises heme to bilirubin, free iron and carbon monoxide (CO). Exhaled CO measurements may therefore reflect an oxidative stress and be clinically useful in the detection and management of inflammatory lung disorders. METHODS: The levels of exhaled CO of 42 non-smoking patients with bronchiectasis treated or not treated with inhaled corticosteroids were compared with CO levels in 37 normal non-smoking subjects. RESULTS: Levels of exhaled CO were raised in patients with bronchiectasis, both those treated with inhaled corticosteroids (n = 27, median 5.5 ppm, 95% CI 5.16 to 7.76) and those not treated with inhaled corticosteroids (n = 15, median 6.0 ppm. 95% CI 4.74 to 11.8), compared with normal subjects (n = 37, median 3.0 ppm, 95% CI 2.79 to 3.81, p = 0.0024). There was no correlation between exhaled CO and HbCO levels (r = 0.42, p = 0.12) in normal subjects (n = 7), nor between the urine cotinine concentration and exhaled CO levels (r = 0.2, p = 0.12). CONCLUSIONS: Increased levels of exhaled CO may reflect induction of HO-1 and oxidative stress in bronchiectasis. Measurement of exhaled CO may be useful in the management of bronchiectasis and possibly other chronic inflammatory lung disorders. (+info)
Pseudomonas aeruginosa is a persistent pathogen in the airways of patients with cystic fibrosis or bronchiectasis from other causes and appears to have evolved strategies to survive the inflammatory response of the host. We hypothesized that the secreted hemolytic phospholipase C (PLC) of P. aeruginosa (PlcHR) would decrease neutrophil respiratory burst activity. We found that while intact wild-type P. aeruginosa cells stimulated moderate respiratory burst activity from human neutrophils, an isogenic mutant pseudomonas (DeltaHR strain) containing a targeted deletion of the plcHR operon induced a much more robust oxidative burst from neutrophils. In contrast, a second pseudomonas mutant (DeltaN) containing a disruption in the gene encoding the nonhemolytic PLC (PlcN) was not different from the wild type in stimulating neutrophil O2.- production. Readdition of purified PlcHR to the DeltaHR strain suppressed neutrophil O2.- production to levels stimulated by wild-type bacteria. Interestingly, purified PlcHR decreased phorbol myristate acetate (PMA)- but not formyl methionyl-leucyl-proline (fMLP)-induced respiratory burst activity, suggesting interference by PlcHR with a protein kinase C (PKC)-specific signaling pathway. Accordingly, the PKC inhibitor bisindolylmaleimide inhibited the oxidative burst induced by either PMA or intact pseudomonas, but not by fMLP, whereas the p38 kinase inhibitor SB-203580 fully inhibited the respiratory burst induced by fMLP or the PlcHR-replete wild-type bacteria, but not PMA or the PlcHR-deficient DeltaHR bacterial mutant. We conclude that expression of PlcHR by P. aeruginosa suppresses bacterium-induced neutrophil respiratory burst by interfering with a PKC-dependent, non-p38 kinase-dependent pathway. (+info)
A resuscitated case from asphyxia by large bronchial cast.
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A 62-year-old woman with bronchiectasis suffered from asphyxia due to a large bronchial cast that obstructed the bronchial tree. Immediate bronchoscopic suction of a bronchial cast of 17 cm in length through the intubated tube relieved the patients without any complications. Large bronchial casts appear to be rare in this century but it should be considered in patients with acute exacerbation of excessive sputa not only in patients with asthma or allergy but also in patients with respiratory tract infection. (+info)
Epidemiological analysis of sequential Pseudomonas aeruginosa isolates from chronic bronchiectasis patients without cystic fibrosis.
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PCR fingerprinting was used for the epidemiological investigation of 64 Pseudomonas aeruginosa isolates collected from 16 chronic bronchiectasis patients without cystic fibrosis: 56% of the patients harbored one clone, 12.5% carried a single major type with minor variants, and 31.5% carried two clones. Only a minority of the acquisitions of antibiotic resistance was related to the acquisition of exogenous strains. Mucoid and nonmucoid sets of isolates did not display any consistent differences in their patterns. The genetic similarity among the clones ranged from 10 to 69%. Cross-infection or common-source exposure did not appear to have occurred. (+info)
A possible mechanism of primary ciliary dyskinesia: a case of a segmental defect in ciliary microtubules.
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We report here a 13-year-old woman with cough, sputum and fever. The patient had both chronic sinusitis and bronchitis. Chest X-ray and computed tomographic scan of the chest revealed mucous bronchial filling and bronchiectasia in bronchi of bilateral lower lobes, right middle lobe and left upper lobe. Aerosol inhalation scintigraphy with 99mTechnetium demonstrated delays of the discharged tracer. On the basis of these findings, primary ciliary dyskinesia was suggested. This was confirmed by the findings from nasal biopsy with transmission electron microscopy where all of the microtubules were segmentally defected near the basal body in the cilia. On the basis of these findings, we diagnosed the patient with primary ciliary dyskinesia which may be due, at least in part, to segmental defect of ciliary microtubules. (+info)
Respiratory epithelial ion transport in patients with disseminated bronchiectasis.
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The nosological limits between disseminated bronchiectasis and cystic fibrosis (CF) remain unclear. In patients with isolated congenital bilateral absence of the vas deferens, a forme fruste of the CF disease, a normal baseline nasal transepithelial potential difference (PD) but an impaired response to pharmacological interventions have been reported. The purpose of the present study was to explore ion transport in respiratory epithelium from patients with disseminated bronchiectasis. The PD under both baseline and pharmacological interventions was investigated in 13 healthy subjects, six patients with genetically proven CF and 15 patients with disseminated bronchiectasis as confirmed by computed tomography scan. Baseline PD was similar in the control and bronchiectasis groups but, as expected, was significantly more negative in the CF group. Patients with bronchiectasis responded to pharmacological tests (sequential perfusion with amiloride, chloride-free solution, isoprenaline and uridine triphosphate (UTP) similarly to healthy subjects. In contrast, CF patients exhibited an increased response to amiloride and an impaired response to chloride-free solution and isoprenaline. The data show that patients with disseminated bronchiectasis exhibit normal electrophysiological properties in their nasal epithelium. Nasal transepithelial potential difference including pharmacological tests may appear a valuable diagnostic procedure for cystic fibrosis with disseminated bronchiectasis. (+info)