Cost of influenza and influenza-like syndromes (I-LSs) in Italy: Results of a cross-sectional telephone survey on a representative sample of general population.

OBJECTIVES: Influenza and Influenza-like syndromes (I-LSs) are very common events in general practice, and their relevance is frequently underestimated. Aim of the study was to assess the economic impact of influenza and Influenza-like syndromes (I-LSs) in the Italian general population by using real-world data from a retrospective database. METHODS: A cross-sectional survey via Computer Assisted Telephone Interview (CATI) was carried out by using a specific questionnaire which is able to assess the rate of infectious episodes, together with subject's behavior in case of influenza or I-LSs, and prescribed therapy. Collected data were statistically analyzed to calculate the economic impact of influenza and I-LSs episodes according to both the National Health System Perspective (NHS-P) and the Italian Families Perspective (S-P). The components of cost were: influenza vaccination, used drugs, General Practitioner (GP) visits, Emergency Room (ER) visits, hospitalizations, and productivity loss. RESULTS: According to the NHS-P, the annual cost for managing influenza or I-LSs amounted to € 60.24, corresponding to € 38.71 per episode. About 72% of the cost was due to GP/ER visits and hospitalization; 22% to drugs, and 6% to vaccination. In the IF-P, the annual cost increased to € 249.70 (€ 140.33 per episode) and almost 90% of the cost was related to workdays lost, while only 11% and 1.3% were due to drugs and vaccination, respectively. Annual cost was highly related to the mean duration of influenza or I-LSs episodes in both perspectives (€ 111─388 in IF-P and € 56─68 in NHS-P). Furthermore, the number of workdays lost due to these episodes showed a significant impact on the overall cost (€ 195─304) only in the NHS-P. CONCLUSIONS: Influenza and I-LSs have a not negligible economic impact, both for the NHS and for the society. Resource consumption is considerable in the NHS-P, while the productivity loss due to people absenteeism causes the most relevant impact in the IF-P.

Patient Related Outcomes-BODE (PRO-BODE): A composite index incorporating health utilization resources predicts mortality and economic cost of COPD in real life.

Multidimensional scores were proposed for defining COPD outcomes, but without any incorporation of the economic COPD cost to clinical indices. AIM: using mortality as an outcome, the hypothesis that adding total health care cost to the BODE index would better predict mortality in COPD was investigated. METHODS: 275 COPD patients were surveyed. Anthropometrics, lung function, the BODE and the Charlson Comorbidity Index were determined. History of exacerbations, ER visits, hospitalizations and mortality were also determined over the next three years, being their rates graded and added to the BODE index according to a simple algorithm. The novel PRO-BODE index ranged 0-10 points; its relationship to annual total COPD cost and survival was assessed by linear regression analysis. RESULTS: total COD cost showed the highest relationship with survival (r = -0.58), even higher than that of age and of BODE index (r = -0.28 and r = -0.21, respectively). The integrated Pro-BODE score proved proportional to the cost of care and inversely proportional to the length of survival. CONCLUSIONS: Pro-BODE is a novel composite index which helps in predicting in real life the impact of COPD over three years, both in terms of patients' survival and of COPD economic burden.

Prevalence of different comorbidities in COPD patients by gender and GOLD stage.

BACKGROUND: Several comorbidities frequently affect COPD progression. Aim of the study was to assess the prevalence of main comorbidities by gender and disease severity in a cohort of COPD patients referring for the first time to a specialist institution. METHODS: The study was a non-interventional, cross-sectional investigation carried out via automatic and anonymous selection from the institutional data base over the period 2012-2015. Inclusion criteria were: subjects of both sex aged ≥40 years; diagnosis of COPD according to GOLD guidelines 2014; the availability of a complete clinical record file. Variables collected were: lung function; smoking history; BMI; the Charlson Comorbidity Index (CCI); number and kind of comorbidities for each patient. RESULTS: At least one comorbidity of clinical relevance was found in 78.6 % of patients, but at least two in 68.8 %, and three or more were found in 47.9 % of subjects. Mean CCI was 3.4 ± 1.6sd. The overall prevalence was 2.6 comorbidities per patient, but 2.5 in males, and 3.0 in females, respectively (p < 0.05). Cardio-vascular disorders were the most frequent, but significantly more frequent in males (44.7 vs 30.7 %, respectively), while the metabolic, the digestive and the osteo-articular disorders were prevailing in females (12.4 vs 9.2; 14.2 vs 4.8, and 6.0 vs 3.8, respectively). In particular, chronic cor pumonale and arrhythmias mainly prevailed in men and congestive heart failure in females, while arterial hypertension resulted equally distributed. As concerning respiratory disorders, pneumonia, pleural effusions and chronic respiratory failure were more frequently found in men, while bronchiectasis and asthma-COPD overlap syndrome (ACOS) in females. Anaemia, gall bladder stones, osteoporosis and spontaneous fractures mostly prevailed in females, while gastric disorders of inflammatory origin and arthrosis were more frequent in males. Cognition disorders, dementia and signs of degenerative brain disorders were more frequently found in men, while depression in females. Finally, lung cancer was at the first place in men, but at the second in females. CONCLUSIONS: All comorbidities increased their prevalence progressively up to the last stage of COPD severity, except the cardio-vascular and the metabolic ones which dropped in the IV GOLD stage, presumably due to the high mortality rate in this severe COPD stage. The gender-dependency of comorbidities was confirmed in general terms, even if lung cancer proved a dramatic increase almost independently of sex.

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.

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.

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.

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.

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.

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.

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.

Health-related quality of life in patients by COPD severity within primary care in Europe.

Pan-European data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) are lacking. This cross-sectional epidemiological study evaluated health status in 1817 COPD patients from an 'all-comers' primary care population in seven European countries (87% stable disease; 13% with current exacerbation) using: St George's Respiratory Questionnaire-COPD specific (SGRQ-C), the short form health survey (SF-12) and the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Mean total score for SGRQ was 44.7 ± 19.4 showing marked impairment of HRQL. Scores differed little between countries (range 39.2-50.1). Impairment was associated with the severity of airway obstruction, but within each GOLD stage the variation (SD) was wide [Stage I: 38.5 ± 19.3 (n = 223); Stage II: 40.4 ± 18.1 (n = 868); Stage III: 50.2 ± 18.6 (n = 551); Stage IV: 58.6 ± 17.7 (n = 144)]. Patients suffering an exacerbation had a worse SGRQ score (54.9 ± 19.3) than those with stable disease (43.3 ± 19.0). The presence of ≥3 co-morbidities (CM) was also associated with a significantly worse score (49.9 ± 19.1) vs. 1-2 CM (42.1 ± 19.1) or no CM (42.3 ± 18.6). Findings with the SF-12 and FACIT-F results were consistent with those from the SGRQ-C. This large observational primary care study shows that health status is significantly impaired in COPD patients of all severities, even in those with mild airway obstruction. Within each GOLD stage of severity there is considerable heterogeneity in HRQL impairment among patients. (Study number: 111749).

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.

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.

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.

Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an open-label randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days.

This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

Importance of inhaler devices in the management of airway disease.

The delivery of drugs by inhalation is an integral component of asthma and chronic obstructive pulmonary disease (COPD) management. However, even with effective inhaled pharmacological therapies, asthma, particularly, remains poorly controlled around the world. The reasons for this are manifold, but limitations of treatment guidelines in terms of content, implementation and relevance to everyday clinical life, including insufficient patient education, access to health care and cost of medication as well as poor inhaler technique are likely to contribute. Considering that inhalation therapy is a cornerstone in asthma and COPD management, little advice is provided in the guidelines regarding inhaler selection. The pressurised metered dose inhaler (pMDI) is still the most frequently prescribed device worldwide, but even after repeated tuition many patients fail to use it correctly. In addition, the correct technique can be lost over time. Although several improvements in pMDIs such as a change in the propellant and actuation have resulted in improvements in lung deposition, many dry powder inhalers (DPIs) are easier to use. However, these devices also have limitations such as dependency of drug particle size on flow rate and loss of the metered dose if the patient exhales through the device before inhaling. Improvements in using inhalation devices more efficiently, in inhaler design for supporting patient compliance, and advances in inhaler technology to assure drug delivery to the lungs, have the potential to improve asthma and COPD management and control. New and advanced devices are considered being helpful to minimise the most important problems patients have with current DPIs.