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Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections in children. It results in about 3.4 million hospitalisations annually in children under five. Palivizumab is an anti-RSV monoclonal antibody, administered intramuscularly at a dose of 15 mg/kg once every 30 days. The efficacy and safety of palivizumab has been evaluated in multicentre, randomised controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost-effectiveness.

OBJECTIVES: To assess the effectiveness and safety of palivizumab prophylaxis compared with placebo, or another type of prophylaxis, in reducing the risk of complications (hospitalisation due to RSV infection) in high-risk infants and children. To assess the cost-effectiveness (or cost-utility) of palivizumab prophylaxis compared with no prophylaxis in infants and children in different risk groups.

SEARCH METHODS: We searched CENTRAL 2012, Issue 7, MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for studies of effectiveness and safety. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012) and Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for economic evaluations.
SELECTION CRITERIA: We included RCTs comparing palivizumab prophylaxis with a placebo, no prophylaxis or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost-effectiveness analyses and cost-utility analyses comparing palivizumab prophylaxis with no prophylaxis.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). We provided a narrative summary of results for continuous outcomes, due to missing data on standard deviations. We performed fixed-effect meta-analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost-effectiveness and/or cost-utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies.

MAIN RESULTS: Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but for most of the outcomes assessed only data from two studies contributed to the analysis. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups.In terms of economic evidence, we included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis compared with no prophylaxis, in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to big differences in cost-effectiveness results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors; and on the cost-effectiveness threshold set by the healthcare sector in each country.

AUTHORS' CONCLUSIONS: There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease or those born preterm.Results from economic evaluations of palivizumab prophylaxis are inconsistent, implying that economic findings must be interpreted with caution. ICER values varied considerably across studies, from highly cost-effective to not cost-effective. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.

Towards a functional proteomics approach to the comprehension of idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis and pulmonary Langerhans cell histiocytosis.

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Towards a functional proteomics approach to the comprehension of idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis and pulmonary Langerhans cell histiocytosis.

J Proteomics. 2013 Mar 23;83C:60-75

Authors: Landi C, Bargagli E, Bianchi L, Gagliardi A, Carleo A, Bennett D, Perari MG, Armini A, Prasse A, Rottoli P, Bini L

Abstract
Bronchoalveolar lavage fluid of patients with four interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis) and smoker and non smoker control subjects were compared in a proteomic study. Principal component analysis was used to statistically verify the association between differentially expressed proteins and the conditions analyzed. Pathway and functional analysis by MetaCore and DAVID software revealed possible regulatory factors involved in specific "process networks" like regulation of stress and inflammatory responses. Immune response by alternative complement pathways, protein folding, Slit-Robo signaling and blood coagulation were "pathway maps" possibly associated with interstitial lung diseases pathogenesis. Four interesting proteins plastin 2, annexin A3, 14-3-3ε and S10A6 (calcyclin) were validated by Western blot analysis. In conclusion, we identified proteins that could be directly or indirectly linked to the pathophysiology of the different interstitial lung diseases. Multivariate analysis allowed us to classify samples in groups corresponding to the different conditions analyzed and based on their differential protein expression profiles. Finally, functional and pathway analysis defined the potential function and relations among identified proteins, including low abundance molecules present in the MetaCore database. BIOLOGICAL SIGNIFICANCE: This is the first study where different interstitial lung diseases such as sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis and smoker and non smoker control subjects were compared in a proteomic study to highlight their common pathways. We decided to report not only principal component analysis, used to statistically verify the association between differentially expressed proteins and the conditions analyzed, but also functional analysis general results, considering all differential proteins potentially involved in these conditions, to speculate about possible common pathogenetic pathways involved in fibrotic lung damage.

PMID: 23528693 [PubMed - as supplied by publisher]

Obstructive sleep apnea is common in patients with interstitial lung disease.

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Obstructive sleep apnea is common in patients with interstitial lung disease.

Sleep Breath. 2013 Apr 8;

Authors: Pihtili A, Bingol Z, Kiyan E, Cuhadaroglu C, Issever H, Gulbaran Z

Abstract
PURPOSE: The incidence of obstructive sleep apnea (OSA) in interstitial lung disease (ILD) has been reported at different frequencies in several studies. The aims of our study were to evaluate the frequency of OSA in ILD and to analyze the relationship between polysomnography (PSG) findings and pulmonary function, disease severity, parenchymal involvement, and Epworth Sleepiness Scale (ESS) scores. METHODS: ILD patients with parenchymal involvement were evaluated. The disease severity was assessed using an index consisting of body mass index (BMI), carbon monoxide diffusion capacity, the Modified Medical Research Council dyspnea scale, and the 6-min walking distance. All of the patients had lung function, chest X-ray, PSG, ESS scoring, and an upper airway examination. Patients with a BMI ≥ 30 or significant upper airway pathologies were excluded. RESULTS: Of 62 patients, 50 patients comprised the study group (14 male, 36 female; mean age 54 ± 12.35 years, mean BMI 25.9 ± 3.44 kg/m(2)) with diagnoses of idiopathic pulmonary fibrosis (IPF; n = 17), stage II-III sarcoidosis (n = 15), or scleroderma (n = 18). The frequency of OSA was 68 %. The mean apnea-hypopnea index (AHI) was 11.4 ± 12.5. OSA was more common in IPF patients (p = 0.009). The frequency of rapid eye movement-related sleep apnea was 52.9 %. The frequency of OSA was higher in patients with a disease severity index ≥3 (p = 0.04). The oxygen desaturation index and the AHI were higher in patients with diffuse radiological involvement (p = 0.007 and p = 0.043, respectively). CONCLUSIONS: OSA is common in ILD. PSG or at minimum nocturnal oximetry should be performed, particularly in patients with functionally and radiologically severe disease.

PMID: 23563999 [PubMed - as supplied by publisher]

Smoking-related interstitial fibrosis (SRIF): pathologic findings and distinction from other chronic fibrosing lung diseases.

Smoking-related interstitial fibrosis (SRIF): pathologic findings and distinction from other chronic fibrosing lung diseases.

J Clin Pathol. 2013 Apr 27;

Authors: Katzenstein AL

Abstract
Smoking-related interstitial fibrosis (SRIF) is a common, histologically striking finding in smokers that must be distinguished from the idiopathic interstitial pneumonias and other chronic interstitial fibrosing lesions. It is characterised by marked thickening of alveolar septa by fibrosis composed of thick collagen bundles that have a distinctive hyalinised quality and often are admixed with variable numbers of hyperplastic smooth muscle fibres. There is minimal accompanying inflammation. This fibrosis is usually most prominent in subpleural and centrilobular parenchyma, but can be present elsewhere as well. It is accompanied by emphysema and respiratory bronchiolitis. Most patients are asymptomatic or only mildly symptomatic, and the clinical course is stable in most. This paper reviews the pathologic features of SRIF in detail, its differentiation from more ominous interstitial fibrosing processes, and the clinical implications of its diagnosis.

PMID: 23626009 [PubMed - as supplied by publisher]

Pseudomonas aeruginosa: new insights into pathogenesis and host defenses.

Pseudomonas aeruginosa is a metabolically versatile bacterium that can cause a wide range of severe opportunistic infections in patients with serious underlying medical conditions. These infections are characterized by an intense neutrophilic response resulting in significant damage to host tissues and often exhibit resistance to antibiotics leading to mortality.

Treatment of persistent infections is additionally hampered by adaptive resistance, due to the growth state of the bacterium in the patient including the microorganism's ability to grow as a biofilm. An array of P. aeruginosa virulence factors counteract host defences and can cause direct damage to host tissues or increase the bacterium's competitiveness. New prevention and treatment methods are urgently required to improve the outcome of patients with P. aeruginosa infections.

This review describes the two main types of P. aeruginosa lung infections and provides an overview of the host response and how the genomic capacity of P. aeruginosa contributes to the pathogenesis and persistence of these infections.

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