Clinical efficacy and safety of budesonide-formoterol in non-cystic fibrosis bronchiectasis.

BACKGROUND: The aim of this study is to evaluate the efficacy and safety of medium-dose formoterol-budesonide combined inhaled treatment in a single inhaler compared with high-dose budesonide treatment in patients with non-cystic fibrosis (non-CF) bronchiectasis. METHODS: This is a 12-month randomized, double-blind, parallel-groups clinical trial, to run in 40 patients with non-CF bronchiectasis diagnosed by high-resolution CT scan of the chest, receiving formoterol-budesonide combined treatment (18/640 µg daily) or budesonide treatment (1,600 µg daily). Variables concerning clinical condition, health-related quality of life (HRQL), lung function, ß(2)-adrenergic agonist use, potentially pathogenic microorganism (PPM) isolates, and medication side effects were analyzed by intention-to-treat analysis. RESULTS: The study group receiving a formoterol-budesonide combined treatment showed a significant improvement, both clinically and statistically, of symptoms (dyspnea, number of coughs, and rescue ß(2)-adrenergic agonist-free days). Furthermore, we observed an HRQL improvement, with no changes in functional parameters or in PPM isolates, together with an important reduction in overall side effects, especially for those related to inhaled steroids, compared with the high-dose budesonide treatment group. CONCLUSIONS: Inhaled medium-dose formoterol-budesonide combined treatment in a single inhaler is more effective and safe compared with high-dose budesonide treatment in patients with non-CF bronchiectasis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00728715; URL: www.clinicaltrials.gov.

[The association between bronchiectasis, systemic inflammation, and tumor necrosis factor alpha]. / Bronquiectasias, inflamación sistémica y factor de necrosis tumoral alfa: factores asociados.

OBJECTIVE: The relationship between systemic inflammation and different measures of bronchiectasis severity has not been described. The objective of this study was to analyze the relationship between plasma concentrations of tumor necrosis factor alpha (TNF-alpha), as a marker of systemic inflammation, and some commonly used criteria for quantifying bronchiectasis severity in clinically stable patients whose disease was not caused by cystic fibrosis. PATIENTS AND METHODS: Sixty-eight clinically stable patients with bronchiectasis and 19 age- and sex-matched healthy control subjects were included in the study. Data on disease history, symptoms, severity, functional variables, sputum volume, and microbiological cultures, laboratory findings, and other indicators of disease course were collected. Plasma concentrations of TNF-alpha were measured using high-resolution enzyme-linked immunoabsorbent assay. RESULTS: Plasma concentrations of TNF-alpha were higher in patients than controls (8.28 vs 5.67 pg/mL; P=.001). This observation correlated with other markers of systemic inflammation such as erythrocyte sedimentation rate (r=0.42; P=.001), C-reactive protein (rho=0.45; P=.001), and percentage of peripheral blood neutrophils (rho=0.45; P=.001). Patients with high plasma concentrations of TNF-alpha (>8.1 pg/dL) had more severe disease (5.19 vs 3.21; P=.001), were more likely to have respiratory failure (37.5% vs 8.3%; P=.003), and a higher rate of Pseudomonas aeruginosa colonization (34.3% vs 8.3%; P=.008). CONCLUSIONS: High plasma concentrations of TNF-alpha were associated with several criteria usually used to assess severity of bronchiectasis in clinically stable patients with disease not caused by cystic fibrosis.

Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis.

BACKGROUND: Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis. METHODS: Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations. RESULTS: Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) [odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p=0.005], more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p=0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p=0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline. CONCLUSION: Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.

[Bronchiectasis in the elderly. Study of serum levels of immunoglobulin G subclasses]. / Bronquiectasias en pacientes mayores de 65 años. Estudio de los valores séricos de las subclases de inmunoglobulina G.

BACKGROUND AND OBJECTIVE: To analyze the serum levels of immunoglobulin G (IgG) subclasses in a broad range of elderly patients with bronchiectasis. PATIENTS AND METHOD: Data were collected from all patients who had a high-resolution chest computerized axial tomography diagnosis of bronchiectasis in our center. We gathered data related to case history, respiratory symptoms, forced spirometry, general laboratory tests, immunoglobulin concentration (including IgG subclasses), Mantoux test, sputum culture and staining, paranasal sinus X-rays/computerized axial tomography, and a specific etiologic evaluation based on the available clinical evidence. RESULTS: A total of 128 patients were included -mean age (standard deviation): 71.6 (5.1) years; range: 65-88; 44.5% males- and 20.3% of them had chronic sputum colonization with Pseudomonas aeruginosa. 28.1% cases had a post-infectious nature and in 40.6% the etiology was unknown. Sixteen patients (12.5%) had decreased levels of at least one of the sIgG compared to normal values. The most frequent deficiency corresponded to IgG2 levels. These subjects showed a characteristic profile of bronchiectasis with an increased lung extension of the disease (p = 0.02); greater presence of cylindrical and diffuse bronchiectasis (p = 0.02 and 0.01, respectively), greater percentage of an unknown etiology (p = 0.004); greater presence of paranasal sinus X-ray abnormalities (p = 0.004) and increased number of past repeated upper airway infections (p = 0.03). CONCLUSIONS: Decreased serum levels of IgG subclasses might be associated with a characteristic profile of bronchiectasis in elderly patients in whom other etiologies have been ruled out.

Inhaled steroids improve quality of life in patients with steady-state bronchiectasis.

BACKGROUND: The effects of inhaled steroids upon the quality of life of patients with bronchiectasis remain unknown. STUDY OBJECTIVE: To analyze the effect of inhaled fluticasone propionate (FP) for 6 months upon the clinical, functional, microbiological and outcome parameters of patients with steady-state bronchiectasis not due to cystic fibrosis, and its repercussions for patient health-related quality of life (HRQoL). DESIGN: Prospective, randomized, double-blind (for effective doses) study. PATIENTS AND INTERVENTIONS: The diagnosis of bronchiectasis was made by high-resolution computed tomography. Ninety-three patients (mean age: 68.5 [8.4]) were randomized to receive 250 microg bid, 500 microg bid or no treatment with inhaled FP for 6 months. Data were collected at baseline and at 1, 3 and 6 months after the start of treatment. HRQoL was assessed using the validated Spanish version of the St. George's Respiratory Questionnaire. RESULTS: The group administered FP 1000 microg daily showed significant improvement in dyspnea (1.03 [2.1]-1.24 [2.2] points; P = 0.01-0.04), sputum production (P = 0.001), days without cough (P = 0.02) and short-acting beta-2 agonists used (P = 0.01) from the first month of treatment, with no changes in pulmonary function, number or severity of exacerbations, or microbiological profile of the sputum. As a result, an improvement in HRQoL was seen in this group after 3 months of treatment (45.4 [14.2] vs. 40.5 [13.9]; P = 0.01). CONCLUSIONS: Inhalatory FP 500 microg bid is effective from the first month of treatment for controlling the symptoms of patients with steady-state bronchiectasis-thus ensuring a significant improvement in HRQoL.

Quality-of-life determinants in patients with clinically stable bronchiectasis.

STUDY OBJECTIVE: To determine the most important variables influencing health-related quality of life (HRQL) in patients with clinically stable bronchiectasis (SB). DESIGN: Cross-sectional study. PATIENTS AND INTERVENTIONS: A total of 86 patients (mean age, 69.5 years; SD, 8.9 years; 64% male) with SB were included. Data were collected on general patient characteristics, symptoms, laboratory findings, the extent of bronchiectasis, functional variables, medication in acute or stable phases, and the number of exacerbations. All patients completed the St. George Respiratory Questionnaire (SGRQ). Univariate and multivariate analyses were performed to identify the variables significantly influencing HRQL in these patients. RESULTS: Different clinical parameters (sputum, dyspnea, cough, and wheezing), spirometric variables, and laboratory parameters (fibrinogen), as well as the extent of bronchiectasis, medication, and the number of exacerbations were significantly correlated to the total questionnaire score, although only dyspnea (r2 = 0.43, p < 0.0001), FEV1 (r2 = 0.33, p < 0.0001), and daily sputum production (r2 = 0.2, p < 0.004) were independently correlated to the total score, globally explaining 55% of the total score variability. Systemic steroid treatment of exacerbations (r2 = 0.17, p < 0.028) and the habitual presence of coughing (r2 = 0.22, p < 0.004) and wheezing (r2 = 0.16, p < 0.013) were in turn independently correlated to the activity and symptoms subscales, respectively. CONCLUSION: Dyspnea, FEV1, and sputum production are the strongest conditioning factors of HRQL in patients with clinically SB.