Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Severe Asthma and Biologics: Managing Complex Patients.

Bronchial asthma is a chronic inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underlying pathophysiological mechanisms (endotypes). The definition of phenotype/endotype is crucial, given the availability of novel biologic agents for patients who do not respond to conventional therapies. Although patients with type 2 severe asthma benefit significantly from treatment with biologics, nonresponders have been identified. Comorbidities worsen the symptoms of asthma and complicate management of the disease. The assessment and treatment of comorbidities is a crucial step, and appropriate management may improve asthma symptoms and morbidity. Among comorbidities, those with a marked negative impact on control despite appropriate treatment include chronic rhinosinusitis with nasal polyps, obesity, bronchiectasis, and immune deficiency. Although asthma is frequently characterized by increased blood eosinophils that release mediators and cytokines and are involved in inflammation of the airway wall, in patients with very high blood eosinophil levels, we must differentiate between isolated severe eosinophilic asthma and asthma in eosinophilic granulomatosis with polyangiitis. In addition, hypereosinophilia may result from specific biological treatment, as in the case of dupilumab. We outline the clinical features of patients with severe asthma whose disease is complex to manage.

Severe asthma: follow-up after one year from the Italian Registry on Severe Asthma (IRSA)

Summary: Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Severe asthma management in the era of biologics: insights of the Italian Registry on Severe Asthma (IRSA).

Summary: Background. The Italian Registry on Severe Asthma (IRSA) is the most recent and largestregistry in Italy. Objective. To improve the knowledge on the clinical and biological features of severe asthma (SA), and to monitor its treatments. Methods. To analyze clinical,functional, inflammatory, and treatment characteristics of severe asthmatics from the IRSA registry. Results. 851 subjects were enrolled. 31.8% and 64.5% of patients were submitted to oral corticosteroids (OCS), and monoclonal antibodies (MABs), respectively. At least tw ocomorbidities affected 77.4% patients. Asthma was uncontrolled in 62.2% patients. Uncontrolled patients had a higher frequency of exacerbations, and hospitalization, showing a highere osinophilic phenotype, a greater use of OCS, and being treated with MAB less frequently. However, uncontrolled patients treated with MAB had a lower use of OCS and a lower rateof hospitalization. Comparing SA patients with atopy and without atopy, the latter showeda greater use of OCS, and more frequent nasal polyposis and osteoporosis. Among SA patients with atopy treated with MAB, 36% were on a treatment targeting the IL-5 pathway. Conclusions and clinical relevance. This study shows the features of the greatest Italian registryof SA patients, revealing at the time of enrollment a poor disease control, and the use of OCSand MABs in about one third and two thirds of patients, respectively. SA is a complex diseasethat requires a more precise phenotyping and a greater disease control.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Relevance of TH2 Markers in the Assessment and Therapeutic Management of Severe Allergic Asthma: A Real-Life Perspective.

BACKGROUND: Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. METHODS: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. RESULTS: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. CONCLUSIONS: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab.

Severe asthma in adolescents and adults: a national, multicenter registry in real life.

Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Drop-out rate among patients treated with omalizumab for severe asthma: Literature review and real-life experience.

BACKGROUND: In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database. RESULTS: In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals. CONCLUSIONS: Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Subglotic malt-lymphoma of the larynx: an unusual presentation of chronic cough.

Extranodal non-Hodgkin lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The most common site of development of primary laryngeal lymphomas is the supraglottic region. In most cases, the presenting symptoms are hoarseness, dysphagia, dyspnea, and cervical lymphadenopathy. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report a case of a primary extranodal marginal zone of mucosa-associated lymphoid tissue (Malt Lymphoma) of the larynx in a 73-year-old non-smoker woman, presented as chronic cough, unresponsive to oral corticosteroid. We present a detailed report of her clinical and paraclinical data as well as treatment options. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes. If a cough persists after consideration of the most common causes, CT scan and a bronchoscopic evaluation are fundamental for the diagnosis of tumors of the upper and lower respiratory tract.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.

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.

N-acetylcysteine as a therapeutic approach to post-COVID-19 pulmonary fibrosis adjunctive treatment.

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.

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.