Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

OBJECTIVE: Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). METHODS: All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. RESULTS: Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were "psychosocial factors" and "burden of having to take medication", respectively. CONCLUSION: A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Epidemiological and virological findings during an outbreak of equine influenza in Uruguay in 2018.

Equine influenza is one of the major respiratory infectious diseases in horses. In 2018, equine influenza virus (EIV) was confirmed as the cause of outbreaks of respiratory disease in horses in Chile and Argentina. In the same year, for the first time in Uruguay, EIV infection was confirmed by isolation and molecular analysis to be the cause of respiratory disease among hundreds of clinically affected thoroughbred horses in training and racing facilities. The virus was detected in nasopharyngeal swabs by a pan-reactive influenza type A realtime reverse transcription polymerase chain reaction (rRT-PCR). The partial nucleotide sequence of the haemagglutinin 1 (HA1 ) gene (994 base pairs) was determined and analysed phylogenetically using MEGA X software. Amino acid sequence alignments were constructed, and serum samples were tested by haemagglutination inhibition and single radial haemolysis. The diagnosis of EIV was confirmed by rRT-PCR, virus isolation and serological testing. The phylogenetic analysis of the partial HA1 gene sequence of the isolated virus indicated that it belongs to clade 1 of the Florida sub-lineage of the American lineage and is closely related to viruses isolated in the recent past. Study of the HA1 region (331 amino acids) of the virus identified in horses in racing facilities in Uruguay displayed the highest amino acid sequence identity with viruses detected in Argentina, Chile and the United Kingdom in 2018. The surveillance data reported illustrate the international spread of EIVs and support the recommendation of the World Organisation for Animal Health (OIE) Expert Surveillance Panel to include viruses of the Florida sub-lineage in vaccines.

La grippe équine est l'une des principales maladies respiratoires infectieuses affectant les équidés. En 2018, il a été confirmé que des foyers de maladie respiratoire enregistrés chez des chevaux au Chili et en Argentine étaient dus au virus de la grippe équine. Cette même année en Uruguay, pour la première fois dans ce pays, il a été établi par isolement viral et par des méthodes moléculaires que le virus de la grippe équine était l'agent causal d'une maladie respiratoire affectant cliniquement des centaines de chevaux pur-sang dans des centres d'entraînement et des hippodromes. La détection du virus s'est faite à partir d'écouvillons prélevés par voie naso-pharyngée en appliquant une technique d'amplification en chaîne par polymérase couplée à une transcription inverse en temps réel (rRT­PCR) à large spectre pour les virus influenza de type A. Une séquence nucléotidique partielle correspondant au gène de l'hémagglutinine 1 (HA1) (994 paires de bases) a fait l'objet d'une analyse phylogénétique au moyen du programme informatique MEGA X. Il a été procédé à la construction d'une matrice d'alignements de ces séquences d'acides aminés. D'autre part, des prélèvements de sérum issus de chevaux atteints ont été soumis à l'épreuve d'inhibition de l'hémagglutination et à une hémolyse radiale unique. Aussi bien la rRT­PCR que l'isolement viral et l'analyse sérologique ont confirmé le diagnostic de l'infection par le virus de la grippe équine. Il ressort de l'analyse phylogénétique du fragment de séquence du gène HA1 du virus isolé que ce dernier appartient au clade 1 de la sous-lignée Florida de la lignée américaine et qu'il est étroitement apparenté à des virus isolés au cours des dernières années. L'étude de la région HA1 (331 acides aminés) du virus détecté chez des chevaux de course en Uruguay a montré que les virus qui présentaient la plus grande similitude avec cette séquence d'acides aminés étaient ceux détectés en Argentine, au Chili et au Royaume-Uni en 2018. Les données de surveillance rapportées illustrent la propagation à l'échelle internationale des virus de la grippe équine et renforcent la recommandation émise par le Groupe d'experts de l'Organisation mondiale de la santé animale (OIE) chargé de la surveillance de la composition des vaccins contre la grippe équine d'inclure les virus de la sous-lignée Florida dans la composition de ces vaccins.

La gripe equina es una de las principales infecciones respiratorias que afectan al caballo. En 2018 se confirmó que el virus de la gripe equina era la causa de diversos brotes de afección respiratoria que habían afectado a caballos de Chile y Argentina. Ese mismo año, por primera vez en el Uruguay, se confirmó por aislamiento y análisis molecular que el virus de la gripe equina era la causa de una infección respiratoria que, acompañada de manifestaciones clínicas, afectó a cientos de caballos purasangre de hipódromos y centros de adiestramiento. El virus fue detectado en muestras de frotis nasales mediante una técnica de reacción en cadena de la polimerasa acoplada a transcripción inversa en tiempo real (rRT­PCR, por sus siglas en inglés) que reacciona ante todos los virus gripales de tipo A. Tras secuenciar parcialmente el gen de la hemaglutinina 1 (HA1 ) (994 pares de bases), se procedió a su análisis filogenético empleando el programa informático MEGA X. Además de crear una matriz de alineamiento de secuencias de aminoácidos, se sometieron muestras de suero a pruebas de inhibición de la hemaglutinación y hemólisis radial simple. Así, el diagnóstico que apuntaba al virus de la gripe equina fue confirmado por rRT­PCR, aislamiento vírico y análisis serológico. El análisis filogenético de la secuencia parcial del gen HA1 del virus aislado puso de manifiesto que pertenece al clado 1 del sublinaje Florida del linaje americano y guarda estrecho parentesco con otros virus aislados en fechas recientes. El estudio de la región HA1 (331 aminoácidos) del virus detectado en caballos de hipódromos uruguayos reveló que el mayor nivel de concordancia de su secuencia de aminoácidos se daba con virus detectados en Argentina, Chile y el Reino Unido en 2018. Los datos de vigilancia comunicados dan fe de la propagación internacional de los virus de la gripe equina y avalan la recomendación formulada por el Panel de expertos en vigilancia de la composición de las vacunas contra la gripe equina de la Organización Mundial de Sanidad Animal (OIE), que aboga por incluir virus del sublinaje Florida en las vacunas.

Efficacy of erdosteine 900 versus 600 mg/day in reducing oxidative stress in patients with COPD exacerbations: Results of a double blind, placebo-controlled trial.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased airway and systemic inflammation. There is evidence that erdosteine accelerates recovery from AECOPD by reducing airway inflammation. AIM: To investigate the dose-dependent antioxidant/anti-inflammatory activity of erdosteine in COPD patients. METHODS: In this single-centre, double blind, double dummy study, patients with mild-to-moderate COPD (GOLD stage II-III), were randomised to receive either placebo or two dosages of oral erdosteine (300 mg tid or 300 mg bid + 1 capsule of indistinguishable placebo) for 28 days in addition to their standard treatment. Primary variables were plasma reactive oxygen species (ROS) and 8-isoprostane levels, while secondary variable was lung function (FEV1; FEV1/FVC; FEV1 short-term reversibility), all assessed in baseline; every two weeks during the study, and one week after the end of the study. RESULTS: Baseline demographic characteristics, plasma ROS and 8-isoprostane levels and lung function were not significantly different in the 24 eligible patients (14 males, aged 38-75 years). At 2 weeks, there was a dose-dependent decrease in ROS in the erdosteine groups. By week 4 there were significant differences in ROS levels compared to baseline between patients receiving 900 mg/day (p < 0.003) and those receiving 600 mg/day (p < 0.04). This effect continued in the follow-up week (p < 0.021). Erdosteine also lowered 8-isoprostane plasma levels after 4 weeks (p < 0.01), and this effect lasted over the post-treatment week. Moreover, % FEV1 reversibility after salbutamol 400 mcg obtained after a 4 -week treatment of erdosteine 900 mg/day was significantly higher than that obtained after 600 mg/day (p < 0.01). Erdosteine was well tolerated and no treatment-related adverse event was reported. CONCLUSIONS: Results confirm the antioxidant dose- and time-dependent activity of erdosteine, and support the utility of including erdosteine it in the therapeutic strategy for the prevention and treatment of oxidative stress-induced inflammation, which frequently leads to AECOPD occurrence.

Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients.

Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently not well controlled, despite intensive guideline-based therapy. The unique monoclonal antibody approved for patients with severe allergic asthma is omalizumab: a recombinant humanised murine against IgE antibodies. The aim of the present study is to investigate the effect of long-term anti-IgE on the thickening of the reticular basement membrane (RBM) and eosinophil infiltration in bronchial biopsies from patients with severe persistent allergic asthma. Biopsies were obtained from 11 patients with severe persistent allergic asthma before and after (12 months) treatment with omalizumab. RBM thickness and eosinophils were measured by using light microscope image analysis. A significant mean reduction in RBM thickness and eosinophil infiltration were measured after one-year omalizumab treatment. No correlation between eosinophil reduction and RBM thickness reduction was found. No correlation between each of the previous two parameters and clinical parameters was detected. In conclusion, our study showed that a substantial proportion of severe asthmatics reduced the original bronchial RBM thickness and eosinophil infiltration after one-year treatment with anti-IgE, thus emphasizing the possible role of omalizumab in affecting airway remodeling in severe persistent allergic asthma.

Pattern of airway inflammation and remodelling in mild persistent atopic asthma and in mild persistent asthma related to gastroesophageal reflux.

BACKGROUND: The increase of basement membrane thickness (BMAT) represents a structural feature described as commonly characterizing airway remodelling in asthma, even if the non-atopic condition had been investigated only episodically from this point of view. Gastrooesophageal-reflux is a pathological condition which can frequently cause and/or sustain asthma in non-atopic individuals. OBJECTIVES: The aim of the study was to measure BMT; some inflammatory mediators in BAL; cys-leucotrienes (LTE4) in urine; e-NO, and BHR to Methacholine (MCh) in mild atopic and in mild non-atopic, GER-related asthma. METHODS: After their informed consent, 25 mild atopic (40.9 years +/- 13.1 sd, FEV1 = 95.9% pred. +/- 12.9 sd) and 39 non-atopic, GER-related asthmatics (57.3 years +/- 14.2 ds, FEVY1 = 101.3% pred. +/- 12.2 sd), nonsmoker and of a comparable asthma duration, underwent measurements of basal lung function and bronchial response to MCh (PD20 FEV1); endobronchial biopsies and BAL (in the right middle lobe), and a 24-h gastroesophageal pHmetry. RESULTS: Atopic GER-related asthma showed two distinct patterns of airway inflammation. The eosinophilic contribution to airway inflammation was systematically prevailing in the former group, such as: EOS = 10.7% +/- 13.4 sd vs 2.0% +/- 2.8 sd, p = 0.001; ECP = 344.9 mcg/l +/- 635.9 sd vs 59.2 mcg/l +/- 75.1 sd, p = 0.001. CONCLUSIONS: Data from the present study are suggesting that persistent mild atopic and mild GER-related asthma seem to represent two distinct phenotypes of asthma in terms of airway remodelling, and in particular of BMT involvement.

Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation.

BACKGROUND: Pulmonary Rehabilitation ("Rehabilitation") can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease (COPD) even if only a very small proportion of patients have access to Rehabilitation. Supplementation of Essential Amino Acids (EAAs) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status. METHODS: 88 COPD out-patients (GOLD class 3-4) with a body mass index (BMI) < 23 Kg/m2 were randomised to receive EAAs (n = 44) or placebo (n = 44) for twelve weeks. Primary outcome measures were changes in both physical activities in daily life (measured by Sense Wear Armband in terms of mean steps walked in one week) and in quality of life (measured by the St George's Respiratory Questionnaire, SGRQ). RESULTS: After 12 weeks, the physical performance was significantly increased vs baseline only in patients who received EAAs (1140.33 +/- 524.69 and 638.68 +/- 662.1 steps/day, respectively; p = 0.02), being also the comparison vs the placebo group highly significant (p = 0.003). Similarly, the SGRQ score improved significantly only in EAA patients (69.35 +/- 9.51 vs baseline 72.04 +/- 8.62; p < 0.01), and changes were significantly different from those measured in the placebo group (p < 0.001). Furthermore, when compared to those who received placebo, EAAs patients significantly increased their fat-free mass (p = 0.04), muscle strength (p < 0.01), saturation of oxygen (p = 0.05), serum albumin (p < 0.001), and also ameliorated their original cognitive dysfunction (p = 0.02). CONCLUSIONS: Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme, together with their quality of life; nutritional and cognitive status, and muscle strength.

Properties of the COPD assessment test in a cross-sectional European study.

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

Changes of clinical outcomes and health care resources in moderate and in severe COPD treated uniquely with tiotropium 18 mcg od for twenty-four months.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease characterized by incompletely reversible bronchial obstruction. The effects of current therapeutic options in early stages of COPD have been poorly investigated in the past, being this specific topic revamped by the results of recent secondary analyses from large international trials. AIM: To measure and monitor in real life the changes in main clinical outcomes and health care resources in patients suffering from mild-to-moderate and severe COPD treated with only tiotropium br. for twenty-four months. METHODS: The population sample of the present observational retrospective study consists of 319 COPD subjects (214 males; average age 71.7 years ± 06 se) automatically extracted from the DataBase of the Health Care Institution. Inclusion criteria were: age ≥ 40 y; basal FEV1 < 80% predicted and FEV1/FVC < 70%; regular treatment with only 18 mcg tiotropium br. for the following two years. All subjects were divided into two subsets according to their FEV1 basal value: (Group A ≤ 50%, and Group B >50% predicted). Lung function; n. exacerbations; n. hospitalizations; absenteeism; n. GP's visits, and use of systemic steroids or antibiotics were checked during the observational period and mean values compared in both subsets with those of the twelve months preceding tiotropium br. (such as during other therapeutic strategies). T test was used for checking the comparability of groups, while ANOVA--Duncan test was used to compare the trends of all variables over time; p < 0.05 was accepted. RESULTS: Group A, 154 individuals (104 males; mean age 72.1 years ± 0.51 se) had a mean FEV1 value of 45.4% pred. ± 0.61 se, while the remaining 165, Group B (111 males; mean age 71.4 years ± 0.60 se) had a mean FEV1 value of 65.5% pred. ± 5.7 se (p < 0,01). The two subsets were well matched for gender, age, and previous use of systemic steroids, but significantly different in terms of basal lung function, COPD morbidity, and antibiotic use. Basically, the impact of COPD confirmed higher in severe patients even if it was unexpectedly remarkable in mild-to-moderate individuals in terms of consumption of health care resources. The overall reduction in COPD morbidity was significant in both groups, but the improvement in FEV1 and in other main long-term outcomes observed in subjects with mild-to-moderate COPD was particularly significant and substantial (p < 0.001), these subjects confirming to be worth of earlier therapeutic attention. CONCLUSIONS: 18 mcg tiotropium br. monotherapy for twenty-four months on a regular daily basis enables a significant minimization of COPD impact, and consents the progressive lung function recovery also in mild-to-moderate individuals, thus suggesting a possible role of tiotropium br. in affecting the natural history of COPD.

Thyroid autoimmunity and pre-term delivery: brief review and meta-analysis.

BACKGROUND: About 10% of women in childbearing age are positive for thyroid antibodies. The presence of such antibodies has been associated with adverse obstetrical outcomes, in particular miscarriage and pre-term delivery, even though the strength of these associations varies widely from one study to another. AIM: To evaluate from the available data of the literature, the association between thyroid autoimmunity and pre-term delivery. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Library search from 1990 to 2010. A combination of key words was used to generate 2 subset of citations, one indexing thyroid antibodies and the other indexing pre-term delivery as adverse outcome. RESULTS: Seven studies, collecting about 23,000 patients were selected. Meta-analysis of the studies showed an association between thyroid autoimmunity and pre-term delivery [odds ratio =1.67 (confidence interval: 1.44- 1.94; p<0.001)]. CONCLUSIONS: The results of the meta-analysis confirmed the association between thyroid autoimmunity and pre-term delivery. A cause-effect relationship has to be still clarified and interventional studies are required.

Erdosteine affects eicosanoid production in COPD.

UNLABELLED: Oxidant-antioxidant imbalance and lipid peroxidation are known to activate the 5-LO pathway with increased expression of inflammatory eicosanoids. Erdosteine has recently shown important anti-oxidant properties, including the ability to reduce 8-isoprostane in COPD patients. AIM: To assess the effects of erdosteine (E) on eicosanoids, and to compare the time-course of effect with that of E anti-oxidant activity. METHODS: 12 moderate COPD patients (9 males, 60 - 78 y) randomly received E 300 mg b.i.d. or placebo (P) for 10 days in a double-blind, controlled design. Blood ROS (Fort/Units); serum LTB4 and urine LTE4 (pg/ml) were measured at baseline and after 1, 3, 5 and 10 days of treatment. Analysis of covariance (ANCOVA) was performed. RESULTS: In COPD patients, both LTB4 and LTE4 dropped significantly during the 10-day treatment with E: s-LTB4 from 136.0 ± 35.4 SD to 54.5 ± 31.2 SD; u-LTE4 from 267.0 ± 91.5 SD to 84.0 ± 64.7 SD, p < 0.001 vs. p from Days 5 and 3, respectively. Moreover, a significant decrease of blood ROS was confirmed in patients using E. FEV1 values slightly increased during erdosteine treatment, whereas a trend to decrease was observed in the placebo group, with a significant difference in favor of erdosteine after 10 days of treatment (p = 0.0088). CONCLUSIONS: 1) The scavenging and anti-inflammatory effects of Erdosteine were both confirmed; 2) erdosteine proved to affect eicosanoids significantly; 3) this novel effect underlines the important anti-inflammatory potentialities of the drug in COPD; 4) further investigation is needed in order to assess the capability of Erdosteine in controlling ongoing inflammation in chronic respiratory diseases.

Reference urinary LTE4 levels in normal individuals: a pilot study.

UNLABELLED: The definition of reference normal values for urinary LTE4 still represents an open question. AIM: to assess the influence of gender and age on urinary LTE4 levels in normal individuals. METHODS: after their informed consent, urinary LTE4 was measured in 124 well matched, non smoker, non atopic subjects (mean age 49.5 y +/- 20.1 sd; range 4-85 y, 57 m;) without any clinically evident disease and not taking any drug for several months. In all subjects, urine were collected in the morning, and processed by an immunoenzimatic method (Cayman Chem, Mi, USA) via the Triturus system (Grifols, Spain). STATISTICS: t test, anova, linear regression, assuming p < 0.05. RESULTS: mean urinary LTE4 were 57.3 pg/ml in males (mean age 51.2 y +/- 21.3 sd) and 57.0 pg/ml in females (mean age 48.1 y + 19.1 sd), p = ns. Linear regression showed no relationship between urinary LTE4 levels and subjects' age in the whole sample of subjects. When subjects were divided according to 4 different classes of age (0-14; 15-40; 41-60; > 60), anova proved that mean urinary LTE4 levels were significantly different in the different classes of age, being higher in younger subjects (67.1 pg/ml +/- 33.4 sd; 69.8 pg/ml +/- 27.5 sd; 57.1 pg/ml +/- 25.4 sd, and 45.1 pg/ml +/- 24.9, respectively) (anova p < .002; Welch test p < .005). CONCLUSIONS: 1) gender does not affect urinary LTE4 levels in normals; 2) mean urinary LTE4 concentrations tend to a slight, but significant, decrease with the increase of the subjects' age, and this is clear in those over-60; 3) reference values for younger and older normal subjects (such as, under- and over-60 years) should be assumed accordingly.

Cost-utility of add-on omalizumab in difficult-to-treat allergic asthma in Italy.

OBJECTIVE: Omalizumab (OM), an innovative biological treatment for difficult asthma with perennial sensitisations, is an humanized monoclonal anti-IgE antibody that binds free circulating IgE; inhibits mast cell and basophil activation by combining free IgE, leads to IgE receptor down-regulation, thus blocking the inflammatory cascade. AIM OF THE STUDY: To assess real-world cost-utility ofadd-on OM in Italy. METHODS: changes in clinical and economical outcomes, and in quality of life (QoL) associated with add-on OM in adults (n=23) with severe dfficult asthma were compared with those recorded before OM in the same subjects. Variables were: lung function; IgE levels; health status; ACT score; QoL (SGRQ); n. GP and specialist visits; emergency visits; hospitalizations, and concomitant pharmacological treatments. Further indices were: changes in Health-related QoL; total health-care costs, and incremental cost/utility. Data were statistically compared (Student's T test), and p < 0.01 was accepted for statistical significance. RESULTS: asthma clinical outcomes and patients' health-related quality of life improved significantly by adding OM, and both costs for drugs and hospital care dropped significantly (p < 0.01). The net economic effect was a 350 Euro increase in overall monthly costs; when related to health benefits, it corresponded to an incremental cost/utility ratio ofabout 26,000 Euro/QALY, which represents a quite favourable figure in terms of willingness to pay for health benefits in industrialised countries. CONCLUSIONS: Omalizumab added to an optimised therapy significantly improves clinical outcomes in difficult-to-treat, persistent allergic asthma. Costs also increased, but proved justified by health benefits achieved.

Use of aerosols in bronchiectasis patients.

Bronchiectasis is a chronic respiratory disease which recognises different etiologies, and characterised by persistent cough, bronchial hypersecretion, airway colonisation with Gram-negative pathogens; frequent infectious exacerbations; progressive lung function decline, and poor quality of life. Several therapeutic strategies are used for managing bronchiectasis, and nebulised medications are regarded with great and ever increasing interest because they allow the direct medication of targets airway structures, higher concentrations of the drug employed, and much less systemic effects. In general terms, the available therapeutic strategies lead to different results depending of whether bronchiectasis are related to cystic fibrosis or not. The effects of the main classes of drugs for aerosol delivery in bronchiectasis patients have been reviewed and updated. Further research is needed in order to ameliorate therapeutic interventions in bronchiectasis, both in terms of new molecules and aerosol formulations to use, and of systems able to optimize drug delivery and drug effectiveness.

[Features of the use of synthetic analogues of thyroid hormones: а 2020 THESIS* questionnaire survey of members of the Belarusian Public Medical Association of Endocrinology and Metabolism].

BACKGROUND: The standard treatment for hypothyroidism is levothyroxine (LT4), which in the Republic of Belarus is available in tablet form whereas liothyronine (LT3) is not registered, but patients can purchase them on their own abroad. AIM: This study aimed to investigate Belarusian endocrinologists' attitude of thyroid hormones in hypothyroid and euthyroid patients. MATERIALS AND METHODS: An online survey was conducted, for which members of the Belarusian Medical Association of Endocrinology and Metabolism were invited by posting information in the group chat and by e-mail. The research period was from October 1 to December 26, 2020. 210 questionnaires were received, 146 of which were used. RESULTS: The majority of participants, 145 (99.3%), indicated that they were using LT4 as the first-choice drug for the treatment hypothyroidism. Sixty-one (41.8%) doctors answered that LT3 + LT4 combination likely can be used in patients with long-term untreated hypothyroidism and 15 (10.3%) - in patients with persistent symptoms of hypothyroidism, despite biochemical euthyroidism on therapy LT4. Over half of the respondents 84 (57.5%) answered that thyroid hormone therapy was never indicated for euthyroid patients, but 50 (34.2%) would consider it for female infertility with high level of thyroid antibodies and 36 (24.7%) for simple goiter growing over time. In various conditions that could interfere with absorption of LT4, most responding Belarusian endocrinologists do not expect a significant difference with different formulations (tablets+"I do not expect major changes in different forms" vs. "soft gel capsules"+"liquid solution"; p <0.001). Persistent symptoms of hypothyroidism on the background of LT4 replacement therapy with the achievement of the target TSH can mainly be caused by psychosocial factors, concomitant diseases, unrealistic patient expectations, chronic fatigue syndrome, and the burden of chronic disease. CONCLUSION: The method of choice of Belarusian endocrinologists in the treatment of hypothyroidism is LT4 replacement therapy, but the appointment of LT4 + LT3 combination therapy can be considered in certain clinical situations. As a rule, endocrinologists do not prescribe LT4 in patients with euthyroidism and do not expect a significant difference when using other forms of levothyroxine.

The prevalence of nasal polyps and the corresponding urinary LTE4 levels in severe compared to mild and moderate asthma.

BACKGROUND: Several comorbid conditions may contribute to worsening asthma symptoms, including nasal polyps (NPs). Cysteinyl leukotrienes (Cys-LTs) play a crucial role in asthma pathophysiology, and specific receptors for CysLTs are reported as upregulated in nasal polyp tissues. The aim of the present study was to assess the prevalence of nasal polyps in severe vs. mild and moderate asthma, and to compare the corresponding levels of urinary Leukotriene E4 (LTE4). MATERIALS AND METHODS: A cohort of 386 asthma patients were studied: n=166 with mild, n=146 with moderate and n=74 severe asthma. All patients performed a nasal endoscopy and urine were collected in the morning for the quantitative LTE4 immunoenzimatic assay (Cayman Chemical, MI, USA). Intolerance to ASA was also assessed by means of a nasal provocation test with L-ASA. RESULTS: The prevalence of NPs was the following: 8 cases (4.8%) in mild; 14 (9.6%) in moderate, and 33 (44.6%) in severe asthma. Mean urinary LTE4 levels were increasing according to the disease severity. ASA-intolerance was assessed in 1 patient in mild asthma (0.6%), 14 in moderate asthma (9.6%) and 28 in severe asthma (37.8%). CONCLUSIONS: Nasal polyps represent a comorbid which is highly frequent in severe asthma. Both their prevalence and the corresponding mean LTE4 levels in urine proved in strict, direct relationship with asthma severity. In severe asthma, nasal polyps represent a condition which is associated with the highest excretion of urinary LTE4 and ASA intolerance.

Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia.

AIM: Aim of the study was to investigate whether or not oral supplementation of essential amino acids (EAAs) may improve body composition, muscle metabolism, physical activity, cognitive function, and health status in a population of subjects with severe chronic obstructive pulmonary disease (COPD) and sarcopenia. METHODS: Thirty-two patients (25 males) (FEV1/FVC < 40% predicted), age 75 +/- 7 years, were randomised (n = 16 in both groups) to receive 4 gr/bid EAAs or placebo according to a double-blind design. When entered the study (T0), after four (T4), and after twelve (T12) weeks of treatments, body weight, fat free-mass (FFM), plasma lactate concentration (micromol/l), arterial PaCO2 and PaO2, physical activity (n degree steps/day), cognitive function (Mini Mental State Examination; MMSE), health status (St. George's Respiratory Questionnaire; SGRQ) were measured. RESULTS: EAAs supplemented, but not patients assuming placebo, progressively improved all baseline variables overtime. In particular, at T12 of EAAs supplementation, body weight (BW) increased by 6 Kg (p = 0.002), FFM by 3.6 Kg (p = 0.05), plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l (p = 0.023), PaO2 increased by 4.6 mmHg (p = 0.01), physical activity increased by 80% (p = 0.01). Moreover, the score for cognitive dysfunction improved from 19.1 scores to 20.8 (p = 0.011), while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance. CONCLUSIONS. A three-month EAAs supplementation may have comprehensive effects on nutritional status; muscle energy metabolism; blood oxygen tension, physical autonomy; cognitive function, and perception of health status in patients with severe COPD and secondary sarcopenia.

Costs of chronic obstructive pulmonary disease (COPD) in Italy: the SIRIO study (social impact of respiratory integrated outcomes).

Chronic respiratory diseases affect a large number of subjects in Italy and are characterized by high socio-health costs. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and costs generated in 1 year by a population of patients with chronic obstructive pulmonary disease (COPD) in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data from COPD patients who reported spontaneously to pneumological centers participating in the study, the corresponding economic outcomes being assessed at baseline and after a 1-year survey. A total of 748 COPD patients were enrolled, of whom 561 [408 m, mean age 70.3 years (SD 9.2)] were defined as eligible by the Steering Committee. At the baseline visit, the severity of COPD (graded according to GOLD 2001 guidelines) was 24.2% mild COPD, 53.7% moderate and 16.8% severe. In the 12 months prior to enrollment, 63.8% visited a general practitioner (GP); 76.8% also consulted a national health service (NHS) specialist; 22.3% utilized Emergency Care and 33% were admitted to hospital, with a total of 5703 work days lost. At the end of the 1-year survey, the severity of COPD changed as follows: 27.5% mild COPD, 47.4% moderate and 19.4% severe. Requirement of health services dropped significantly: 57.4% visited the GP; 58.3% consulted an NHS specialist; 12.5% used Emergency Care and 18.4% were hospitalized. Compared to baseline, the mean total cost per patient decreased by 21.7% (p<0.002). In conclusion, a significant reduction in the use of health resources and thus of COPD-related costs (both direct and indirect costs) was observed during the study, likely due to a more appropriate care and management of COPD patients.