In many respiratory diseases characterized by an intense inflammatory response, the balance between proteolytic enzymes (proteases, including elastases) and their inhibitors (proteinases inhibitors) ...is not neutral. Excess activity of neutrophil elastase (NE) and similar proteases has been reported to cause tissue damage and to alter the remodeling process in many clinical conditions such as pneumonia, respiratory distress, and acute lung injury (ALI). Several experimental NE inhibitors have been tested in preclinical and clinical studies of different conditions of inflammatory lung injury such as ALI and pneumonia, with contrasting results. This study reviews the literature regarding NE inhibitors in the field of respiratory diseases and reflects on possible future developments. In particular, we highlight potential gaps in the scientific evidence and discuss potential strategies for focusing investigation on antielastases in clinical practice through the selection of targeted populations and proper outcomes.
Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity.
The aim of the ...present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity.
We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society.
Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease.
Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.
Bronchiectasis (BE) is a chronic and heterogeneous respiratory disease that requires a multidimensional scoring system to properly assess severity. The aim of this study was to compare the severity ...stratification by 2 validated scores (BSI and FACED) in a BE cohort and to determine their predictive capacity for exacerbations and hospitalizations. Moreover, we proposed a modified version of FACED which was created to better predict the risk of exacerbations in clinical practice. We performed a prospective cohort study including BE patients >18 years old with a follow-up period of 1-year. One-hundred eighty-two patients (40% males; mean age 68) were studied. Patients were stratified according to the number of exacerbations during the follow-up, and according to BSI and FACED scores. BSI classified most of our patients as severe 99 (54.4%) or moderate 47 (25.8%), while FACED mainly classified as mild 108 (59.3%) or moderate 61 (33.5%). BSI and FACED showed an area under ROC curve (AUC) for exacerbations of 0.808 and 0.734; and for hospitalizations (due to BE exacerbations) of 0.893 and 0.809, respectively. Subsequently, we modified FACED by adding previous exacerbations (Exa-FACED) and this new score classified patients as mild 48.4%, moderate 34.6% and severe 17.0%, with an improved AUC for exacerbations (0.760) and hospitalizations (0.820). Despite previous validations of BSI and FACED, they classified our patients very differently. As expected, FACED showed poor prognostic capacity for exacerbations. We support the Exa-FACED score to predict the risk future exacerbations for been easy to use in clinical practice.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more ...susceptible to acquire pathogens with antibiotic resistance. We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations.
A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared. Multidrug-resistance was determined according to European Centre of Diseases Prevention and Control classification.
Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes. Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016). Three independent multidrug-resistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92-30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37-11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02-15.46). The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors.
Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations. This information may assist clinicians in choosing empirical antibiotics in daily clinical practice.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis.
The Bronchiectasis Radiologically Indexed CT Score (BRICS) was ...devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients.
A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV1, sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV1, 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging.
A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis.
Evaluation of interventions on road traffic injuries (RTI) going beyond the assessment of impact to include factors underlying success or failure is an important complement to standard impact ...evaluations. We report here how we used a qualitative approach to assess current interventions implemented to reduce RTIs in Peru.
We performed in-depth interviews with policymakers and technical officers involved in the implementation of RTI interventions to get their insight on design, implementation and evaluation aspects. We then conducted a workshop with key stakeholders to analyze the results of in-depth interviews, and to further discuss and identify key programmatic considerations when designing and implementing RTI interventions. We finally performed brainstorming sessions to assess potential system-wide effects of a selected intervention (Zero Tolerance), and to identify adaptation and redesign needs for this intervention.
Key programmatic components were consistently identified that should be considered when designing and implementing RTI interventions. They include effective and sustained political commitment and planning; sufficient and sustained budget allocation; training, supervision, monitoring and evaluation of implemented policies; multisectoral participation; and strong governance and accountability. Brainstorming sessions revealed major negative effects of the selected intervention on various system building blocks.
Our approach revealed substantial caveats in current RTI interventions in Peru, and fundamental negative effects on several components of the sectors and systems involved. It also highlighted programmatic issues that should be applied to guarantee an effective implementation and evaluation of these policies. The findings from this study were discussed with key stakeholders for consideration in further designing and planning RTI control interventions in Peru.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The epidemiological profile and trends of road traffic injuries (RTIs) in Peru have not been well-defined, though this is a necessary step to address this significant public health problem in Peru. ...The objective of this study was to determine trends of incidence, mortality, and fatality of RTIs in Peru during 1973-2008, as well as their relationship to population trends such as economic growth.
Secondary aggregated databases were used to estimate incidence, mortality and fatality rate ratios (IRRs) of RTIs. These estimates were standardized to age groups and sex of the 2008 Peruvian population. Negative binomial regression and cubic spline curves were used for multivariable analysis. During the 35-year period there were 952,668 road traffic victims, injured or killed. The adjusted yearly incidence of RTIs increased by 3.59 (95% CI 2.43-5.31) on average. We did not observe any significant trends in the yearly mortality rate. The total adjusted yearly fatality rate decreased by 0.26 (95% CI 0.15-0.43), while among adults the fatality rate increased by 1.25 (95% CI 1.09-1.43). Models fitted with splines suggest that the incidence follows a bimodal curve and closely followed trends in the gross domestic product (GDP) per capita.
The significant increasing incidence of RTIs in Peru affirms their growing threat to public health. A substantial improvement of information systems for RTIs is needed to create a more accurate epidemiologic profile of RTIs in Peru. This approach can be of use in other similar low and middle-income settings to inform about the local challenges posed by RTIs.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work revisits the potential of Solid/Gas (S/G) biocatalysis for sustainable ester synthesis, focusing on isobutyl propionate (isoPro) production from propionic acid (aciP) and isobutyl alcohol ...(isoB) using CalB Immo Plus™ (CalB-IP), Candida antarctica lipase B (CalB) supported on ECR1030M (ECR). Our research, conducted in a bench-scale S/G bioreactor, describes the role of adsorption-desorption and intraparticle mass transfer on the production rate of isoPro. Three reaction scenarios were examined at 55°C: simultaneous introduction of both substrates into the reactor; CalB-IP saturation with isoB followed by the supply of aciP; and vice versa, with aciP saturation preceding isoB. Adsorption-desorption-based experiments were conducted to determine breakthrough curves for isoB, aciP, and isoPro over ECR or CalB-IP at 55°C. ECR exhibited significant adsorption capacity, with aciP>isoPro>isoB, in a reversible process. At pseudo-steady state, aciP and isoB were adsorbed at 86% and 84%, respectively, on ECR; while the remaining 14% and 16%, respectively, were adsorbed on the enzyme surface, involving irreversible binding. The experimentation also considered the influence of water activity (aw: 0.11–0.75) on experimental responses. Production rates of isoB adsorption and isoPro were sensitive to aw, while aciP adsorption remained insensitive to aw. At aw = 0.75, isoB adsorbed 35% less over CalB-IP than at aw = 0.11. Additionally, at aw = 0.75, the production of isoPro at the bioreactor outlet in the pseudo-steady state was 33.5% less than when aw = 0.11. These findings offer valuable insights for designing S/G bioreactors, thereby advancing the industrial implementation of sustainable ester synthesis.
Display omitted
•Solid/Gas biocatalysis using CalB Immo Plus™ for ester synthesis was evaluated.•Unexpected adsorption-desorption mechanism impacted isobutyl propionate production.•Adsorption-desorption mechanism was linked to the structural properties of ECR1030M.•Higher initial water activity values impacted both alcohol and ester adsorption.•Findings offer valuable insights for optimizing biocatalyst and bioreactor design.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background It is general belief that Non-cystic fibrosis bronchiectasis (NCFB) is characterized by frequent community-acquired pneumonia. Nonetheless, the knowledge on clinical ...characteristics of CAP in NCFBE is poor and no specific recommendations are available. We aim to investigate clinical and microbiological characteristics of NCFBE patients with CAP. Methods Prospective observational study of 3495 CAP patients (2000–2011). Results We found 90 (2.0%) NCFBE-CAP that in comparison with non-bronchiectatic CAP (n, 3405) showed older age (mean ± SD, NCFBE-CAP 73 ± 14 vs . CAP 65 ± 19yrs), more vaccinations (pneumococcal: 35% vs. 14%; influenza: 60% vs . 42%), comorbidities (n ≥ 2: 43% vs. 25%), previous antibiotics (38% vs. 22%), and inhaled steroids (53% vs. 16%) (p < 0.05 each). Streptococcus pneumoniae was the most frequent isolate in both groups (NCFBE-CAP 44.4% vs. CAP 42.7%; p = 0.821) followed by respiratory virus, mixed infections and atypical bacteria. Considering overall frequencies of the main pathogens (including monomicrobial and mixed infections) Pseudomonas aeruginosa (15.5% vs. 2.9%; p < 0.001) and Enterobacteriaceae (8.8% vs. 2.4%; p = 0.025) were more prevalent in NCFBE-CAP patients than in CAP. Despite these clinical and microbiological differences, NCFBE-CAP showed similar outcomes to CAP patients (mortality, length of hospital stay, etc.). Conclusions NCFBE-CAP patients are usually older and have more comorbidities but similar outcomes than general CAP population. Usual CAP pathogens, such as S. pneumoniae , are also involved in NCFBE-CAP but P. aeruginosa and other Enterobacteriaceae were globally more frequent than in CAP. Therefore, a wide microbiological investigation should be recommended in all NCFBE-CAP cases as well as routine pneumococcal vaccination for prevention of pneumonia.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In order to determine sleep habits in bus drivers and their relationship to accidents in the city of Arequipa, Peru, a cross-sectional descriptive study was conducted in a non-probabilistic sample of ...166 drivers. Driving hours per day were 9.4 ± 3.7. 54% (89) drive over 4 hours without stopping; 74% (123) drive at night; and 87% (145) sleep on the bus. 75% reported fatigue while driving (124). 27% (45) had drowsiness; 24% (40) reported having been in or on the verge of an accident while driving. Sleepiness or fatigue while driving was common in this population and their driving and rest habits could contribute to this.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
