New evidence in severe pneumonia: imipenem/ cilastatin/relebactam.

Imipenem combined with beta-lactamase inhibitor relebactam (IMI/REL) has an extensive bactericidal activity against Gram-negative pathogens producing class A or class C beta-lactamases, not active against class B and class D. The phase 3 clinical trial (RESTORE-IMI-2), double-blind, randomized, evaluated IMI/REL vs. piperacillin-tazobactam (PIP/TAZ) for treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), demonstrated non-inferiority at all-cause mortality at 28 days (15.9% vs 21.3%), favorable clinical response at 7-14 days end of treatment (61% vs 59.8%) and with minor serious adverse effects (26.7% vs 32%). IMI/REL is a therapeutic option in HAP and VAP at approved dosage imipenem 500 mg, cilastatin 500 mg and relebactam 250 mg once every 6h, by an IV infusion over 30 min.

Depression and anxiety symptoms in Spanish adult patients with cystic fibrosis: associations with health-related quality of life.

BACKGROUND: Cystic fibrosis (CF) is a chronic disease with an impact on the quality of life. Self-reported symptoms of depression and anxiety were assessed in the Spanish cohort of the International Epidemiological Study on Depression and Anxiety in patients with CF (International Depression-Anxiety Epidemiological Study) and their relationship with health status and health-related quality of life (HRQoL) was evaluated. METHODS: This cross-sectional study recruited adult patients with CF at 10 Spanish centers. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Revised Cystic Fibrosis Questionnaire. Demographic and health data were recorded from medical charts. Logistic regression was used to determine the predictors of elevated symptoms of depression and anxiety (HADS≥8). RESULTS: Of the 336 participants recruited (mean age, 28.1years; 48.2% women), 41 (12.2%) had elevated depression-related scores, and 100 (29.7%) had elevated anxiety-related scores (HADS≥8). After adjusting for confounders, only less education, intravenous antibiotics, psychiatric medications and psychotherapy were significantly associated with elevated psychological symptoms. Specifically, regardless of lung function, patients who were depressed or anxious reported worse HRQoL. CONCLUSIONS: The prevalence of elevated symptoms of depression and anxiety was high in Spanish adult patients with CF, and these symptoms were associated with a decreased HRQoL.

Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

Reduced expression of galectin-1 and galectin-9 by leucocytes in asthma patients.

Accumulating evidence shows that galectins play roles in the initiation and resolution phases of inflammatory responses by promoting anti- or proinflammatory effects. This study investigated the presence of three members of the galectin family (galectin-1, -3 and -9) in induced sputum samples of asthma patients, as well as their possible implication in the immunopathogenesis of human asthma. Levels of interleukin (IL)-5, IL-13, and galectins were determined in leucocytes isolated from induced sputum samples by reverse transcription-polymerase chain reaction (RT-PCR) immunofluorescence and flow cytometry. High levels of IL-5 and IL-13 mRNA were detected in sputum cells from asthma patients. In parallel, immunoregulatory proteins galectin-1 and galectin-9 showed a reduced expression on macrophages from sputum samples compared with cells from healthy donors. In-vitro immunoassays showed that galectin-1 and galectin-9, but not galectin-3, are able to induce the production of IL-10 by peripheral blood mononuclear cells from healthy donors. These findings indicate that macrophages from sputum samples of asthma patients express low levels of galectin-1 and galectin-9, favouring the exacerbated immune response observed in this disease.

Lymphangioleiomyomatosis: a study of 72 patients from the Spanish registry.

BACKGROUND: Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease that almost exclusively affects young women of childbearing age. The true incidence and prevalence of LAM are unknown. This study was conducted to evaluate the characteristics of lymphangioleiomyomatosis in Spain. METHODS: Over a 2-year period, a questionnaire designed for this study was collected. This questionnaire included sociodemograhic, clinical, radiological and functional data. Information about the study and this questionnaire were both sent by e-mail to all the participants of the interstitial disease registry of 2004. RESULTS: Seventy-two patients, all of whom were women, were included in the registry, with a mean age of 44.56 +/- 11.1 yr. Sixty-three patients (87.5%) presented the sporadic LAM and 9 (12.5%) presented LAM associated with tuberous sclerosis (LAM-TS). LAM diagnosis was confirmed with an open lung biopsy in 57 patients (79.2%) and was performed with thoracic HRCT compatible with LAM diagnosis in the other 15 cases. The most frequent symptom was dyspnoea (90%) followed by cough (44.4%). Almost 40% of patients presented renal angiomyolipomas in the study and the most frequent spirometric pattern was obstructive in more than half of the patients. Most patients with LAM-TS (88.8%) had renal angiomyolipomas compared with 31.7% in the sporadic LAM group. CONCLUSION: The characteristics of the Spanish population affected with LAM are similar to those of other countries. Most patients were symptomatic, had a history of previous pneumothorax and presented abnormal radiological findings and pulmonary function tests.

[Cystic fibrosis in adults: inter- and intraobserver agreement for the Brasfield and Chrispin-Norman chest radiography scoring systems and correlation with clinical data and spirometry]. / Fibrosis quística en adultos: acuerdos inter e intraobservador para las escalas de puntuación de Brasfield y Chrispin-Norman en la radiografía de tórax y relación con datos clínicos y espirométricos.

OBJECTIVE: Most chest radiography scoring systems for patients with cystic fibrosis have been developed for children but are also used for adults. Our aim was to evaluate the intra- and interobserver variability of 2 radiographic scoring systems in adults with cystic fibrosis and to assess the correlation of these systems with clinical and spirometric parameters. PATIENTS AND METHODS: The chest x-rays of 24 adult patients with cystic fibrosis were compared using 2 scoring systems (Brasfield and Chrispin-Norman). The x-rays were scored by 2 radiologists and reevaluated 4 months later by 1 of the 2 observers. Intra- and interobserver agreement was assessed using the intraclass and Pearson's correlation coefficients. The radiographic scores were compared to lung function tests and other clinical data. RESULTS: Both intra- and interobserver agreement were high (r > or = 0.9 and the intraclass correlation coefficient > or = 0.85 with both systems for both samples). Both scoring systems correlated with spirometry results: forced expiratory volume in the first second (FEV1) (r = 0.64 and r = 0.55), FEV1% (r = 0.75 and r = 0.72), and the percentage of forced vital capacity in relation to the predicted value (r = 0.63 and r = 0.056). We found no association between scoring system and sex, age, or body mass index. CONCLUSIONS: Assessment of chest radiographs of adult patients with cystic fibrosis by the Brasfield and Chrispin-Norman scoring systems shows good intra- and interobserver agreement. Both systems correlate well with lung function variables, especially FEV1.

[Nontuberculous mycobacteria in patients with cystic fibrosis]. / Micobacterias ambientales en pacientes adultos con fibrosis quística.

OBJECTIVE: Patients with cystic fibrosis are at great risk of infection by nontuberculous mycobacteria from the environment because of certain predisposing factors such as bronchiectasis, malnutrition, and diabetes. The aim of this study was to analyze the mycobacterial content of sputum smears and cultures from adult patients with cystic fibrosis attended at a specialized unit for adults from March 1997 through December 2001. PATIENTS AND METHODS: Sputum samples were collected prospectively according to a protocol applied at each visit, and during most exacerbations staining and culture for mycobacteria were ordered in addition to the usual cultures for bacteria and fungi. A tuberculin test was performed at the end of the study. RESULTS: Twenty-eight patients (16 men) with cystic fibrosis were enrolled. The mean (SD) age was 25.3 (6.7) years. A total of 251 samples were cultured (range in number of samples per patient, 1-31). The mean period of follow up was 40.3 (22.1) months. The sputum smear was positive in 29 cases (4 patients); the culture was positive in 7 patients. More than 3 samples were positive in only 4 patients. Mycobacterium abscessus was isolated in 3 cases, Mycobacterium avium complex in 2 and Mycobacterium simiae in 1 and other an unidentified rapid growth Mycobacterium species. The Mantoux test was positive in 5 patients. Two of the 4 patients in whose samples mycobacteria were isolated repeatedly required treatment. CONCLUSIONS: The prevalence of nontuberculous mycobacterial infection is high in patients with cystic fibrosis. Staining and culture for mycobacteria should be carried out regularly and whenever exacerbation of pulmonary symptoms cannot be attributed to bacteria usually found in such patients. Patients with recurrent isolations of mycobacteria should be monitored closely.

[Polyradiculitis and Wegener's granulomatosis]. / Polirradiculitis y enferedad de Wegener.

Wegener's granulomatosis is a systemic vasculitis of unknown etiology, primarily affecting the upper and lower respiratory tract and the kidneys, although there is a form restricted to the lungs. Wegener's granulomatosis occurs infrequently, with an estimated annual incidence of 8.5 cases per million. The principal symptoms at onset usually involve the upper and lower airway. The central nervous system is involved in approximately 22% of cases, but neurological signs occur infrequently among the initial clinical manifestations. Proteinase 3-specific antineutrophil cytoplasmic antibodies are useful serological markers for establishing a diagnosis, which should, however, be confirmed by a tissue biopsy of the affected organ.

[Production of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages from patients with rheumatoid arthritis and interstitial pulmonary disease]. / Producción de factor de necrosis tumoral alfa e interleucina 6 por los macrófagos alveolares de pacientes con artritis reumatoide y enfermedad pulmonar intersticial.

The aim of this study was to measure the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by alveolar macrophages in patients with rheumatoid arthritis and interstitial lung disease (ILD). Rheumatoid arthritis patients diagnosed by ACR criteria (n = 8) with associated ILD documented by pulmonary function tests and high resolution computerized tomography scanning, and 12 healthy volunteers (6 smokers and 6 nonsmokers). We determined the spontaneous and induced production of bacterial lipopolysaccharides (LSP), TNF-alpha and IL-6 by alveolar macrophages obtained by bronchoalveolar lavage. The macrophages were isolated by Ficoll-Hypaque gradient centrifugation and plastic adherence and cultured in serum-containing medium (low endotoxin) in the presence and absence of LPS (100 ng/ml). TNF-alpha and IL-6 levels contents were determined in supernatants by ELISA. In the patient group both spontaneous and induced production of TNF-alpha were significantly higher than in controls (p < 0.01). Macrophages stimulated with LPS in patients with rheumatoid arthritis and ILD also released greater amounts of IL-6 than did those of the healthy controls. IL-6 spontaneous and induced production was significantly lower in smokers than in nonsmokers. TNF-alpha and IL-6 production in patients with rheumatoid arthritis and ILD, studied in bronchoalveolar lavage specimens reveals that alveolar macrophages are hyperreactive in these patients, who are possibly sensitized as a consequence of the inflammatory lung process inherent to the disease. Further study is needed to define the pathogenic role of these mediators.