Explore the vast range of titles available.

The prevalence of catheter-associated bloodstream infections (CLABSI) is high and is a severe health problem associated with an increase in mortality and elevated economic costs. There are discrepancies related to the risk factors of CLABSI since the results published are very heterogeneous and there is no synthesis in the description of all the predisposing factors. We aimed to perform a systematic review and meta-analysis to synthesize and establish the risk factors predisposing to CLABSI reported in the literature. This is a systematic review of observational studies following the PRISMA recommendations. MEDLINE and CINAHL databases were searched for primary studies from 2007 to 2021. The protocol was registered in PROSPERO CRD42018083564. A total of 654 studies were identified, 23 of which were included in this systematic review. The meta-analysis included 17 studies and 9 risk factors were analyzed (total parenteral nutrition (TPN), chemotherapy, monolumen and bilumen catheters, days of catheterization, immunosuppression, kidney disease and diabetes mellitus) due to the homogeneity of their definitions and measurements. The risk factors found to increase the probability of developing CLABSI were TPN, multilumen devices, chemotherapy treatment, immunosuppression and the number of days of catheterization. On the other hand, monolumen devices presented a lower likelihood of triggering this infection.

Pulmonary emphysema, a component of chronic obstructive pulmonary disease (COPD) is characterised by irreversible alveolar tissue destruction and is produced by an imbalance between proteolytic enzymes, mostly neutrophil elastase (NE), and its inhibitors, mainly alpha-1 antitrypsin (AAT). We measured elastase-inhibitory activity (EIA) in serum samples and determined whether there is an association between EIA and COPD severity. This cross-sectional study recruited COPD patients with and without severe alpha-1 antitrypsin deficiency (AATD) and healthy controls. A semi-automated method assessed EIA using a porcine elastase inhibition assay. EIA levels and the EIA/AAT ratio were compared across groups and the correlation with clinical variables was analysed. A total of 86 individuals were recruited: 36 COPD patients, 20 individuals with COPD associated with AATD (Pi*ZZ mutation), of whom 11 were on augmentation therapy, and 30 healthy controls. Positive, linear and significant relationships were observed between EIA and AAT levels. The EIA/AAT ratio was higher in non AATD-related COPD patients compared to untreated Pi*ZZ patients and controls. Further analysis in non-AATD-related COPD patients revealed a higher EIA/AAT ratio associated with older age, higher comorbidity burden and a trend towards higher severity of lung disease. The strong correlation between AAT levels and EIA suggests that the assay technique employed is robust and effective for assessing EIA. The EIA assay may serve as a potential biomarker for the assessment of the severity and prognosis of emphysema.

Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www.clinicaltrials.gov (ID: NCT04180319)

To evaluate the tolerance and effectiveness of standard doses (StD) and low doses (LoD) of inhaled antibiotics (IA), in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). Single-center, observational, retrospective, follow-up study of patients with COPD and CBI by PA treated with IA between 2012 and 2021. One year before and one after the first IA dose were analysed. 87 patients were included (86 men) with a mean FEV1(%) of 46.3%. Intolerance to IA was observed in 54 (62.1%), with a median time of 30 days (IQR: 15, 90). Only a higher FEV1(%) was associated with lower probability of intolerance (hazard ratio: 0.98, 95% confidence interval 0.97 to 0.99; p = 0.021). Seven of 15 (46.6%) patients who did not tolerate StD tolerated LoD. Those unable to tolerate LoD also had worse FEV1(%) (38.4% (SD:18.7%) versus 48.1% (SD: 16.4%); p = 0.018). Treatments lasting 6–12 months improved symptoms and reduced PA isolations (− 2.1; P < 0.001) and exacerbations (-1.7, P < 0.001). In 19 patients LoD treatment reduced exacerbations (-2.1, P = 0.003), days of hospitalization (-7.4, P = 0.036) and PA isolations (-2, P = 0.001) with clinical improvement. Antimicrobial resistance was not observed in any case receiving LoD of IA. More than half of our COPD patients treated with IA for CBI by PA presented respiratory intolerance during the first three months related to greater severity of airway obstruction. Treatment with LoD of IA appears to be an effective and safe alternative for some patients unable to tolerate StD.

The prevalence of catheter-associated bloodstream infections (CLABSI) is high and is a severe health problem associated with an increase in mortality and elevated economic costs. There are discrepancies related to the risk factors of CLABSI since the results published are very heterogeneous and there is no synthesis in the description of all the predisposing factors. We aimed to perform a systematic review and meta-analysis to synthesize and establish the risk factors predisposing to CLABSI reported in the literature. This is a systematic review of observational studies following the PRISMA recommendations. MEDLINE and CINAHL databases were searched for primary studies from 2007 to 2021. The protocol was registered in PROSPERO CRD42018083564. A total of 654 studies were identified, 23 of which were included in this systematic review. The meta-analysis included 17 studies and 9 risk factors were analyzed (total parenteral nutrition (TPN), chemotherapy, monolumen and bilumen catheters, days of catheterization, immunosuppression, kidney disease and diabetes mellitus) due to the homogeneity of their definitions and measurements. The risk factors found to increase the probability of developing CLABSI were TPN, multilumen devices, chemotherapy treatment, immunosuppression and the number of days of catheterization. On the other hand, monolumen devices presented a lower likelihood of triggering this infection.

Existing data on COPD prevalence are limited or totally lacking in many regions of Europe. The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, when real data are few and widely separated. Therefore, in order to represent cartographically the prevalence of COPD in Europe, an IDW interpolation mapping was performed. The point prevalence data provided by 62 studies from 19 countries (21 from 5 Northern European countries, 11 from 3 Western European countries, 14 from 5 Central European countries, and 16 from 6 Southern European countries) were identified using validated spirometric criteria. Despite the lack of data in many areas (including all regions of the eastern part of the continent), the IDW mapping predicted the COPD prevalence in the whole territory, even in extensive areas lacking real data. Although the quality of the data obtained from some studies may have some limitations related to different confounding factors, this methodology may be a suitable tool for obtaining epidemiological estimates that can enable us to better address this major public health problem.

Background The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results The study included 1007 individuals, with PI*SS ( n  = 56; 5.6%), PI*ZZ ( n  = 578; 57.4%) and PI*SZ ( n  = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p  = 0.037), COPD (41.4% vs. 60%, p  = 0.002), and emphysema (23.2% vs. 51.9%, p  < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. Conclusions We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. Trial registration www.clinicaltrials.gov (ID: NCT04180319).

Background Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data. Methods We analysed a total of five mutations (four not previously described) in a total of six subjects presenting moderate to severe AATD: Gly95Alafs*18, Val210Glu, Asn247Ser, Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile. Clinical data, genotyping and phenotyping assays, structural mapping, and conformational characterization through molecular dynamic (MD) simulations were developed and combined. Results Newly discovered AAT missense variants were localized both on the interaction surface and the hydrophobic core of the protein. Distribution of mutations across the structure revealed Val210Glu at the solvent exposed s4C strand and close to the “Gate” region. Asn247Ser was located on the accessible surface, which is important for glycan attachment. On the other hand, Asp341His, Leu383Phe were mapped close to the “breach” and “shutter” regions. MD analysis revealed the reshaping of local interactions around the investigated substitutions that have varying effects on AAT conformational flexibility, hydrophobic packing, and electronic surface properties. The most severe structural changes were observed in the double- and triple-mutant (Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile) molecular models. The two carriers presented impaired lung function. Conclusions The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.

Purpose Impaired health-related quality of life (HRQoL) is associated with poor health outcomes in chronic obstructive pulmonary disease (COPD). The aim of this study was to determine health utilities in patients with COPD and to identify the variables with the greatest impact. Methods This is a pooled analysis of data from 4 observational studies performed in stable COPD patients. Evaluation of patient HRQoL utilities was performed using the Spanish version of the self-administered EuroQoL 5 Dimensions (EQ-5D) questionnaire. EQ-5D utilities were described and compared according to several markers of disease severity. Results 6198 patients reported a mean (SD) EQ-5D index of 0.67 (0.26). A linear dose response relationship between EQ-5D utility and modified Medical Research Council (mMRC) score, forced expiratory volume in one 1 s (% predicted), COPD hospital admissions in the previous year, self-reported daily walking time, Charlson index, body mass index, obstruction, dyspnoea and exacerbation (BODEx) index, COPD assessment test (CAT), hospital anxiety and depression scale was observed ( p for trend < 0.001). In multivariate analysis, patients reporting lower utility values were those with more dyspnoea, more comorbidities, using long-term oxygen therapy, with previous hospitalisations due to a COPD exacerbation and higher (worse) CAT score. Conclusion HRQoL measures such as EQ-5D can assist clinicians to understand the impact of respiratory disease on COPD patients.

Background Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. Method This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. Results A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). Conclusions Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.