Assessment of cystic fibrosis severity

Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, The 6th International Medical Congress for Students and Young Doctors, May 12-14, 2016Introduction. Cystic fibrosis (CF) is one of the most common hereditary diseases and being characterized by chronic lung injury, exocrine pancreatic insufficiency and nutrition disorders. In this disease the mutation of the CFTR gene lead to changes of sodium chloride metabolism inside and outside epithelial cells found in he lungs, liver, pancreas, digestive tract and reproductive system. Thus, the result of this malfunction is represented by sticky and thick mucus, salty taste of the sweat and thickened digestive juices which can clog the lumen and alveoli of the lungs (clinically difficult breathing, formation of the environment proned to bacteria growth) or may disturb (when the pancreas is mainly involved) the process or proper digestion and absorbtion of nutrients, leading even to organ failure insevere cases (lungs, pancreas). Pulmonary involvement in CF reflects the severity of the disease and represents the major cause of death.Major criteria used to assess CF severity are based on the evaluation of the lung function. Materials and methods. Our study included 60 patients (the average age 9.08±1.01 years) diagnosed with cystic fibrosis. CF severity was assessed using Shwachman-Kulczycki score, which is based on the following criteria: overall activity of the patient, physical examination results, nutritional status, and data of the chest X-ray examination. Each category was assigned from 1 to 25 points, while the total score ranged from 4 to 100 points maximum (severe ≤40 points, 40-55 points – moderate; mild – 56-70 points, 71-85 points – good, and excellent – 86-100 points). Results and discussions. The Shwachman-Kulczycki score of just 25.46±2.09 points, that indicates a severe evolution of CF, was registered at 46.81% of children with severe malnutrition, but also in older patients with advanced lung diseases. For 25.92% of children the score was 53.57±0.63 points, that means moderate evolution of cystic fibrosis. In 15.6% of patients the Shwachman-Kulczycki score showed a favorable clinical evolution, with a summary of 62.12±0.98 points. Only 12.77% of children had mild form of the diseases with a good score of 78.0±1.30 points. In the study group there were no children identified to have with excellent clinical condition, because of the presence of changes in clinical status and paraclinical tests. Conclusion. The Shwachman-Kulczycki score that includes clinical and imaging criteria, is a very simple to use tool, demonstrated to be highly informative in assessing the clinical status of patients with cystic fibrosis and is recommended to be used in the work of specialists in pediatrics

Cytokinegene polymorphisms and asthma susceptibility, severity and associated allergic manifestations in Moldovan children

Introduction: Asthma is a complex inflammatory disease, caused by the interaction of genetic and environmental factors, and its management requires understanding of its various pathogenesis and control mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. The reported racial and/or ethnic differences in asthma-related loci define the importance of the candidate gene research in ethnically diverse populations. The study was aimed to investigate the association between cytokine gene polymorphisms asthma in a sample of Moldovan patients and controls. Methods: The sample comprised 90 individuals with asthma, aged from 5 to 17 years (mean ±SEM age of 10,9±0,4 years), 51 males and 39 females, who were randomly selected from a group of asthmatic children referred to the Allergy Clinic of the Research Institute for Maternal and Child Healthcare, Chisinau, Moldova, during the years 2009-2010. The control group included 90 healthy children, matched by sex and age with patients’ group (mean age 13,5±0,2), without respiratory symptoms or history of asthma and allergy. Asthma was defined according to the criteria of the Global Initiative for Asthma (GINA). A complete clinical history, physical examination, and pulmonary function test (PFT) in a standard fashion were performed for all the subjects. TNF-a G-308A, IL-4 C-590T and IL-4Ra Arg55lGln polymorphisms were evaluated by polymerase chain reaction. Results: The genotypes frequency for TNF-ct, IL-4, and IL-4Ra were equally distributed in the patient group in comparison with the controls. However, there were significant differences for IL-4 C-590T gene between the subgroups of asthmatics with different degree of the disease severity. Thus, IL-4 CT+TT at position -590 was significantly overrepresented in children with severe asthma in comparison with those with the moderate one (53,8% in severe asthma vs 25,0% in moderate asthma; x2=2,7; gl=l; p=0,086). The same difference was found for the T allele (minor allele): 34,6% in severe asthma vs 12,5% in patients with moderate asthma (x2=5,3; gl=l; p<0,05). The study showed that the homozygous genotype TNF-a GG at position -308 has a protective role, being significantly more frequently identified in children with solitary form of asthma compared with those with allergic triad (86,2% vs 60,0%, respectively; x2—3,88; gl=l; p<0,05). Functionally compromised genotypes TNF-a GA+AA at position -308 were found more frequently in children with asthma associated with other allergic symptoms (40,0% in allergic triad and 55,6% in asthma cases associated with atopic dermatitis vs 13,8% solitary asthma, p<0,05). Conclusions: The results of our study suggested an association between the IL-4 polymorphism at position -590 and asthma severity, and the association of the functionally compromised genotypes of the TNF-a polymorphism at position -308 with different clinical phenotypes of asthma in Moldovan children

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The effectiveness of 13-valent pneumococcal vaccine against community acquired pneumonia in young children: a systematic review and meta-analysis

Objective. The present meta-analysis study aimed to evaluate the effectiveness of 13-valent pneumococcal conjugate vaccine (PCV) in reducing the morbidity from pneumonia among children under 5 years old. Material and methods. Cochrane and Medline electronic databases were systematically searched for studies reporting effectiveness of 13-valent pneumococcal conjugate vaccine against pneumonia among children of the foreseen age group. To assess the effect measure, we used the odds ratio (OR) with 95% confidence intervals (95% CI) for dichotomous outcomes. The heterogeneity of the studies was assessed using I2 and Chi2 statistics. Outcomes. The meta-analysis found a non-significant association between vaccinated children and the development of community-acquired pneumonia (OR=0.50; CI 95%: 0.44-0.57; Chi2=6.07; I2=18%). Vaccine effectiveness (VE) of 13-valent PCV was calculated as (1 – Mantel-Haenszel OR in vaccinated children compared to unvaccinated children) x100%. Thus, the VE of PCV 13 valent was estimated to be about 50%, according to the meta-analysis of the included studies. Conclusions. Our study showed that the group of vaccinated children experienced 50% fewer cases of pneumonia than they would have had if they had not been vaccinated. These data bring additional evidence that vaccination is an effective strategy to prevent community acquired pneumonia in young children

Correlation between serumige and seroconversion of specific antibodies against atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae) and respiratory syncytial virus in patients with bronchial obstruction of atopic or infectious etiology

Introduction: Asthma onset in children is frequently associated with respiratory infections of different etiology: atypical bacteria such as Chlamydia pneumoniae (CPN) or Mycoplasma pneumoniae (MPN), and/or viruses (Respiratory syncytial virus (RSV), Rhinovirus). Recent researches showed that acute viral infection determines a structural susceptibility through inflammatory changes, and may facilitate asthma development in atopic children. However the contribution of each factor to asthma pathogenesis is still controversial. Materials and methods: A case-control study included 129 children hospitalized in the Allergy and Pulmonology wards of the Research Institute for Maternal and Child Healthcare: the first group included 84 children with persistent asthma; the second group included 45 children with bronchial obstruction of infectious etiology. Specific antibodies were assessed using immunoenzymatic assay ELISA. Specific immunoglobulin classes A and G against CPN and MPN and immunoglobulin classes M and G against RSV were evaluated. The total serum immunoglobulin-E (IgE) titres were assessed. Statistical processing of the data was performed using the software Microsoft Excel and STATISTICA 6.0. Results: The specific antibody seroconversion for the examined infections have been found in both study groups. In the first group of patients hospitalized with asthma exacerbation diagnostic titers of antibodies were detected as follows: against MPN in 8,8% of asthma cases, against CPN in 2,9% and RSV in 11,8% of cases. Antibody response to associated infections was detected for MPN+CPN in 5,9% of children; MPN+VRS in 11,8% of children; CPN+VRS in 2,9%. Estimation of these antibodies presence in the group of children with bronchial obstruction showed the presence of anti-MPN immunoglobulins in 6,6% of cases, anti-CPN immunoglobulins in 4,4% of cases and anti-VRS immunoglobulins in 8,8% of patients. No associated infections were found in this study group. Serum IgE levels were raised from the cut off value in 91,2% of the subjects from the asthma group and in 28,9% from the second group. In addition to that, the serum IgE levels in children with asthma exacerbation was 1,5 folds higher comparing with those serologically negative (916,0±236,0 IU/ml and 647,9±104,6 IU/ml respectively, p>0,05) and correlated significantly with anti- MPN immunoglobulin G (r = 0,58). Also an inverse correlation was found between the serum IgE levels and anti-RSV immunoglobulin M (r = -0,53, p<0,01). Conclusions: Infectious factors especially Mycoplasma pneumoniae have a direct impact on asthma pathogenesis, allergic sensitization and serum IgE synthesis. Respiratory syncytial virus seems to have a role in the mechanisms of bronchial obstruction onset mostly through the increase of bronchial hyperreactivity. Thus, the intensity of allergic inflammation in respiratory airways is inversely correlated with the degree of inflammation caused by RSV

Nedraugiška ugnis: kaip tabako pramonė griauna mūsų vaikų ateitį

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned by European Union legislation. Accelerating numbers of young people are vaping, and this does not reflect an exchange of vapes for cigarettes. The acute toxicity of e-cigarettes is greater than that of tobacco, and includes acute lung injury, pulmonary haemorrhage and eosinophilic and lipoid pneumonia. Given the worse acute toxicity, it should be impossible to be complacent about medium and long term effects of vaping. Laboratory studies have demonstrated changes in lung proteomics and the innate immune system with vaping, some but not all of which overlap with tobacco. It would be wrong to consider vapes as a weaker form of tobacco, they have their own toxicity. Children and young people are being targeted by the vaping industry (which is largely the same as the tobacco industry), including on-line, and unless an efficient legislative program is put in place, a whole new generation of nicotine addicts will result