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.

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.

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.

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.

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.

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.

Cultural and linguistic testing of the Handling Questionnaire: a specific instrument for assessing the patient's acceptability of dry powder inhalers.

The testing and checking phases of a questionnaire are briefly described in this paper, identifying the common errors due to incorrect formulation of questions and the main issues. The theoretical methods for "testing" a questionnaire has been examined in the first section, in the second section the testing process for a specific questionnaire for assessing the patient's acceptability of a dry powder device (the Handling Questionnaire) has been described, together with the grading of improvement achieved.

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.

Costs of asthma in Italy: results of the SIRIO (Social Impact of Respiratory Integrated Outcomes) study.

Bronchial asthma is a costly disease and the correlated social impact is ever increasing. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and the costs generated in 1 year by asthmatic patients investigated 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 of 577 patients with bronchial asthma who reported spontaneously to the pneumology centers involved in the study. Of these, 485 patients (300 f, mean age 49.2 years+/-16.3 S.D.) were eligible for analysis. At the baseline visit, the asthma severity was as follows: 26.2% intermittent, 37.1% mild persistent, 29.5% moderate, and 6.6% severe. In the 12 months prior to enrollment, 243 patients (50.1%) had visited the general practitioner (GP); 349 (72%) consulted a National Health Service (NHS) specialist; 68 (14%) utilized Emergency Care; and 50 (10.3%) had been admitted to hospital on account of asthma, with a total of 2059 work days lost. At the end of the 1-year survey, asthma severity changed as follows: 32.8% intermittent, 38.1% mild persistent, 23.7% moderate, and 4.3% severe, with a substantial drop in corresponding outcomes: 39.6% visited their GP, 51.5% visited an NHS specialist, 5.2% used Emergency Care, and 4.3% were admitted to hospital. Compared to baseline, the total average cost per patient decreased globally by 17.9% (p<0.001) after the 1-year survey. In conclusion, during the study period we observed a significant decline in health resources consumption and thus in asthma cost of illness, even though specific costs for the pharmaceutical treatment of asthma increased substantially. These results are likely due to a more strict control of patients and to their more appropriate clinical management.

Urinary LTE4 is higher after nasal provocation test with L-ASA in bronchial than in only nasal responders.

UNLABELLED: Aspirin induced asthma (AIA) is a syndrome characterised by intolerance to acetylsalycilic acid (ASA), nasal polyps and bronchial asthma, being the metabolic shift of arachidonic acid toward the lipoxygenase pathway and hyper-production of cysteinyl-leukotrienes (cys-LTs) the current pathogenetic hypothesis. The research for both sensitive indicators and safe diagnostic tests is still attracting. Aim of the study was to compare the levels of urinary LTE4 in baseline and after Nasal Provocation Test (NPT) with L-ASA from subjects affected by aspirinin-Intolerance and characterized by only a nasal response to ASA to those from subjects with both a nasal and a bronchial response to the same challenge. METHODS: After their written consent, 74 subjects with mill to moderate AIA (16 male, mean age 45.3 years +/- 12.3 sd, mean basal FEV1 = 78.1% pred. +/- 6.2.4sd, FEV1 reversibility = 14.3% bsln +/- 2.1 ds after salbutamol 200 mcg) performed a NPT with L-ASA (total maximal dose 25 mg). Spirometry (FEV1), acoustic rinometry (nasal volume--VOL; nasal Resistance--Req; AR; TM Hood Lab., USA), and urinary LTE4 (Cayman Chemical, MI, USA, via Triturus System, Grifols, Spain) were checked in all subjects in basal conditions and 90' after NPT. STATISTICS: t test between means +/- sd, assuming p < 0.05, and linear regression between all variables considered. RESULTS: In 69 ASA-intolerant-asthmatics, mean FEV1 did not change significantly following NPT (78.7% pred. +/- 5.1 sd in baseline; 78.5% pred. +/- 4.1 sd after NPT, p = ns) even though in the presence of a significant decrease of VOL. (12.6 cm3 +/- 4.1 sd in baseline; 6.2 cm3 +/- 4.6 sd after NPT, p = 0.003); of a substantial increase in Req (0.9 cm H2O/l/min +/- 0.1 ds in baseline; 2.4 cmH2O/l/min +/- 0.2 after NPT, p = 0.04), and of urinary LTE4 excretion (333.0 pg/mg +/- 161.7 in bsln; 558.0 pg/mg +/- 171.690' after NPT with L-SA, p = 0.02). In only 5 subjects, the nasal response occurred concomitantly to a significant bronco-constriction after the NPT: mean FEV, changed from 77.9% pred. +/- 3.9 in bsln to 46.6% pred. +/- 4.3 after NPT (p < 0.001); mean VOL from 13.9 cm3 +/- 4.7 sd to 5.6 cm3 +/- 2.8 sd (p < 0.001); mean Req from 1.1 cmH2O/l/min +/- 0.2 in bsln to 2.5 cmH2O/l/min +/- 0.4 after NPT (p = 0.02) in these subjects. In ASA-intolerant bronchial responders, the severity of respiratory reactions proved related to the extent of urinary LTE4 response, which on the other hand, proved significantly higher than that observed in ASA-intolerant subjects with only nasal response and in ASA-tolerant subjects (LTE4 from 333.0 pg/mg +/- 161.7 in baseline up to 558.0 pg/mg +/- 171.6 90 min. following the NPT with L-ASA the nasal-responders, p = 0.04, but from 412.0 pg/mg +/- 102.8 in baseline up to 978.0 pg/mg +/- 108.7 after NPT in bronchial responders, p < 0.001 from baseline). CONCLUSIONS: Nasal challenge with ASA affects significantly both nasal VOL and Req, and LTE4 excretion in all ASA-intolerant subjects. During the nasal challenge, severity of respiratory reactions proves associated with the highest basal LTE4 synthesis. This feature reflects a spectrum of respiratory tract reactions where cysteinil-LTs can play a specific diagnostic role.

PIKO-1, an effective, handy device for the patient's personal PEFR and FEV1 electronic long-term monitoring.

BACKGROUND AND AIM: Subjects with airway obstruction are strongly recommended to monitor their lung function, which is particularly variable in asthma. Unlike PEFR, other personal measurements (such as FEV1) are still difficult to perform. PIKO-1 is the first electronic device for both PEFR and FEV1 personal check, but its precision has not yet been assessed. The aim of this study was to compare PEFR and FEV1 values from PIKO-1 and from a conventional spirometer in subjects with airway obstruction. METHODS: In total, 352 subjects (217 men; 47.6 +/- 19.0 years; 72.6 +/- 15.0 kg; 168.1 +/- 11.9 cm) performed sequential measurements using a PIKO-1 device and a spirometer. Wilcoxon signed-rank test and sign test were used as statistical tests. RESULTS: Mean FEV1 values from the spirometer and PIKO-1, respectively, were 2.9 L +/- 1.1 and 3.0 L +/- 1.1, and mean PEFR values were 466.1 L/min +/- 164.5 SD and 426.3 L/min +/- 151.6 SD. PIKO-1 proved to overestimate FEV1 values by 4% (p<0.0001) and to underestimate PEFR values by 8% (p<0.000) systematically. CONCLUSIONS: The precision of both PIKO-1 measurements (such as FEV1 and PEFR) have been assessed. PEFR and FEV1 measures should be reset by two different constants. Nevertheless, PIKO-1 is a suitable and reliable device for the personal monitoring of obstructive patients in real life.

Brittle asthma.

Brittle asthma is a clinical phenotype of the disease at the severe end of the spectrum. Type 1 brittle asthma is characterised by a maintained wide PEF variability (> 40% diurnal variation for > 50% of the time over a period of at least 150 days) despite considerable medical therapy including a dose of inhaled steroids of at least 1500 pg of beclomethasone or equivalent. Type 2 brittle asthma is characterised by sudden acute attacks occurring in less than three hours without an obvious trigger on a background of apparent normal airway function or well controlled asthma. Mechanisms behind the development of brittle asthma include smooth muscle contraction and edema of the airways, which are supported by chronic airway inflammation. Allergy reactions, impairment of local immunity, respiratory infections, psycho-social disorders and reduced perception of worsening airway function are the risk factors for brittle asthma. The diagnosis is based on the analysis of specific symptoms, role of triggers, personal or family history, measurement of lung function and PEF monitoring. Pharmacological treatment of type 1 brittle asthma in addition to the high doses of inhaled and/or oral steroids and bronchodilators includes subcutaneous injections of beta2 agonist and inhalation of long acting beta2 agonist. The treatment of patients with type 2 brittle asthma includes exclusion of allergen exposure, identification of triggers, self management and management of acute attacks.