Organization, Clinical and Management Indicators on the First Year of Activity of an Outpatient Clinic Dedicated to the Diagnosis and Treatment of Severe Asthma in Italy.

PURPOSE: A Regional Technical Commission was set in 2017 by Veneto region (Italy) to provide opinions and recommendations on drug prescriptions and to implement treatment-pathway guidelines for severe asthma. In this observational study, we describe the first structured, integrated, multidisciplinary, patient-centered outpatient clinic for the care of severe-asthma patients in Italy, and characterize patients referring to the center for specialist visits. PATIENTS AND METHODS: To characterize patients that accessed the outpatient clinic in 2018, data on demographic characteristics, treatments, severity of asthma, phenotypes, and relevant comorbidities by phenotype were collected. Use of biologic agents and indicators of the performance of the outpatient clinic were described. RESULTS: A structured multidisciplinary outpatient pathway for taking charge of patients and for administration and monitoring of biological agents was developed. A total of 146 patients accessed the outpatient clinic in 2018: 62.3% had uncontrolled asthma upon admission and 27.4% were already being treated with biologic agents. Among patients with uncontrolled asthma, 66% had severe uncontrolled asthma, 22% had moderate-severe uncontrolled asthma, and 12% had mild-moderate uncontrolled asthma. Main asthma phenotypes in uncontrolled-asthma patients were allergic (58% of patients), eosinophilic (22%), allergic plus eosinophilic (10%) and non-atopic asthma (10%). Among patients affected by severe asthma, 47% had allergic asthma, 28% had eosinophilic asthma, 13% had allergic plus eosinophilic asthma, and 12% had non-atopic asthma. Nasal polyps were more frequent in eosinophilic and allergic plus eosinophilic asthma, while gastro-esophageal reflux disease was more frequent in non-atopic asthma. CONCLUSION: This structure of an outpatient clinic for the treatment of severe asthma, with its dedicated pathway and multidisciplinary approach, may allow a stricter control of asthma and optimization of therapies, as well as minimization of drug misuse.

Recommendations from the Italian intersociety consensus on Perioperative Anesthesia Care in Thoracic surgery (PACTS) part 1: preadmission and preoperative care.

INTRODUCTION: Anesthetic care in patients undergoing thoracic surgery presents specific challenges that necessitate standardized, multidisciplionary, and continuously updated guidelines for perioperative care. METHODS: A multidisciplinary expert group, the Perioperative Anesthesia in Thoracic Surgery (PACTS) group, comprising 24 members from 19 Italian centers, was established to develop recommendations for anesthesia practice in patients undergoing thoracic surgery (specifically lung resection for cancer). The project focused on preoperative patient assessment and preparation, intraoperative management (surgical and anesthesiologic care), and postoperative care and discharge. A series of clinical questions was developed, and PubMed and Embase literature searches were performed to inform discussions around these areas, leading to the development of 69 recommendations. The quality of evidence and strength of recommendations were graded using the United States Preventative Services Task Force criteria. RESULTS: Recommendations for preoperative care focus on risk assessment, patient preparation (prehabilitation), and the choice of procedure (open thoracotomy vs. video-assisted thoracic surgery). CONCLUSIONS: These recommendations should help pulmonologists to improve preoperative management in thoracic surgery patients. Further refinement of the recommendations can be anticipated as the literature continues to evolve.

Recommendations from the Italian intersociety consensus on Perioperative Anesthesa Care in Thoracic surgery (PACTS) part 2: intraoperative and postoperative care.

INTRODUCTION: Anesthetic care in patients undergoing thoracic surgery presents specific challenges that require a multidisciplinary approach to management. There remains a need for standardized, evidence-based, continuously updated guidelines for perioperative care in these patients. METHODS: A multidisciplinary expert group, the Perioperative Anesthesia in Thoracic Surgery (PACTS) group, was established to develop recommendations for anesthesia practice in patients undergoing elective lung resection for lung cancer. The project addressed three key areas: preoperative patient assessment and preparation, intraoperative management (surgical and anesthesiologic care), and postoperative care and discharge. A series of clinical questions was developed, and literature searches were performed to inform discussions around these areas, leading to the development of 69 recommendations. The quality of evidence and strength of recommendations were graded using the United States Preventive Services Task Force criteria. RESULTS: Recommendations for intraoperative care focus on airway management, and monitoring of vital signs, hemodynamics, blood gases, neuromuscular blockade, and depth of anesthesia. Recommendations for postoperative care focus on the provision of multimodal analgesia, intensive care unit (ICU) care, and specific measures such as chest drainage, mobilization, noninvasive ventilation, and atrial fibrillation prophylaxis. CONCLUSIONS: These recommendations should help clinicians to improve intraoperative and postoperative management, and thereby achieve better postoperative outcomes in thoracic surgery patients. Further refinement of the recommendations can be anticipated as the literature continues to evolve.

Low adherence to inhaled corticosteroids/long-acting ß2-agonists and biologic treatment in severe asthmatics.

Less than half of severe asthmatic patients show a >80% adherence rate to inhaled treatment just before and during biologic therapy. This has implications in biologic treatment sustainability and disease prevalence estimation. http://bit.ly/3cRTJB0.

Mepolizumab for severe eosinophilic asthma: a real-world snapshot on clinical markers and timing of response.

Background: Few studies have provided real-world evidence of mepolizumab efficacy and safety. We aimed to evaluate mepolizumab for severe eosinophilic asthma in daily clinical practice.Research design and methods: Patients included in the RINOVA (Interdisciplinary Network for the management of severe asthma in Veneto region, Italy) database were investigated. Blood eosinophil count, forced expiratory volume in 1 second, % of predicted (FEV1%), fractional exhaled nitric oxide (FeNO), asthma control test (ACT), oral steroid (OCS) intake, and exacerbation rate were evaluated during mepolizumab treatment.Results: 69 patients were enrolled (mean age: 55.1 years; 60.9% females). A significant improvement was detected at one month with respect to blood eosinophils (median level at baseline: 710/µl; -620/µl, p < 0,001), FEV1% (median value at baseline 87; range: 79-101; +4, p = 0.001) and ACT (median value at baseline 18; range: 14-20.5;+4, <0.001). A significant reduction of FeNO was observed six months after the treatment start, when the exacerbation rate and the mean OCS dose significantly decreased (respectively: Δ reduction -3; p < 0.001 and -5 mg; p < 0.001).Conclusions: Our study provides real-world evidence of mepolizumab safety and confirms its dramatic steroid sparing effect. The greatest clinical change (ACT and FEV1) was observed within the first month.

Cost-effectiveness of the COPD Patient Management European Trial home-based disease management program.

Purpose: Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET). Methods: Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores. Results: Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR -37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR -806 per patient per year) and Spain (EUR -51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany. Conclusion: Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers.

COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.

An international randomized study of a home-based self-management program for severe COPD: the COMET.

INTRODUCTION: Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management. The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions. DESIGN: Multicenter parallel randomized controlled, open-label superiority trial. SETTING: Thirty-three hospitals in four European countries. PARTICIPANTS: A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD. INTERVENTION: The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Comparator is the usual management as per the center's routine practice. MAIN OUTCOME MEASURES: Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs.

Cognitive dysfunction in severe chronic obstructive pulmonary disease (COPD) with or without Long-Term Oxygen Therapy (LTOT).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory condition which can lead to comorbidities of variable severity, cognitive dysfunction included. The role of supplemental oxygen in preventing COPD-induced cognitive deterioration is still debated, but only episodically investigated. The aim of this study was to compare the cognitive pattern of hypoxemic COPD subjects treated with long-term oxygen (LTOT) to that of patients of comparable severity assuming oxygen on irregular basis, and to normal reference values. METHODS: Lung function, arterial blood gases, health status, and cognitive function measured by means of four psychometric tests focusing different domains of cognition (such as: MMSE, Clock test; TMT-A; TMT-B) were assessed in 146 well matched hypoxemic COPD patients (males n = 96, 66%; mean age = 70.5 ± 12.9). Seventy-three patients were assuming long-term oxygen (LTOT), while the remaining seventy-three were only using oxygen as needed (AN). Regarding statistics, t test and ANOVA (Duncan test) were used to analyze data, assuming a p < 0.05 as the lowest limit of significance. RESULTS: Even though all COPD patients showed a poorer psychometric profile vs corresponding normal reference values, LTOT patients showed a lower prevalence of severe deterioration in cognition. Also the extent of impairment was significantly lower in these patients when assessed by TMT-A and TMT-B (p < 0.012 and 0.001, respectively), but not when measured by MMSE and Clock test (both p = ns). Several domains of cognition are variably affected by persistent hypoxemia in COPD patients. A panel of psychometric tools is needed for identifying the pattern of cognitive dysfunctions in these patients. Memory and attention (functions assessed by MMSE and Clock test) are only mildly-moderately affected, while visual processing, reproduction of numeric sequences, cognition flexibility, and shifting capacity (functions assessed by TMT-A and TMT-B) are much more deteriorated (p < 0.012 and p < 0.001, respectively). CONCLUSIONS: Only LTOT allows to preserve significantly (p < 0.022) cognitive functions from the COPD-induced deterioration. This assumption is of strategic value for COPD patients who are prescribed long-term oxygen because they frequently are not aware of the cognitive risks related to their condition.

Costs of illness analysis in Italian patients with chronic obstructive pulmonary disease (COPD): an update.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide, and its epidemiological, clinical, and socioeconomic impact is progressively increasing. A first estimate of the economic burden of COPD in Italy was conducted in 2008 (the SIRIO [Social Impact of Respiratory Integrated Outcomes] study). The aim of the present study is to provide an updated picture of the COPD economic burden in Italy. METHODS: Sequential patients presenting at the specialist center for the first time during the period 2008-2012 and with record file complete (demographic, clinical, lung function, and therapeutic data; health care resources consumed in the 12 months before the enrollment and for the 3 subsequent years) were selected from the institutional database. RESULTS: Two hundred and seventy-five COPD patients fitting the inclusion criteria were selected (226 males; mean age: 70.9 years [standard deviation: ±8.4 years]; 45.8% were from the north, 25.1% from central Italy, and 29.1% from south Italy). COPD-related average costs per patient in the 12 months before enrollment were as follows: hospitalization: €1,970; outpatient care: €463; pharmaceutical: €499; and indirect costs: €358. Average direct costs and total societal costs were €2,932 and €3,291, respectively. Direct cost was €2,461 (hospitalization: €1,570; outpatient: €344; and pharmaceutical: €547) in the first year of follow-up, while total societal cost was €2,707. No significant difference was reported in any cost category between sexes. CONCLUSION: The therapeutic approach followed in a specialist center, based on the application of clinical guidelines, has been shown to be a highly effective investment for the long-term management of COPD. A small increase of pharmaceutical costs per year allowed a substantial saving in terms of hospitalizations, costs related to outpatient services, and indirect costs.

Extent and prevalence of cognitive dysfunction in chronic obstructive pulmonary disease, chronic non-obstructive bronchitis, and in asymptomatic smokers, compared to normal reference values.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) can affect cognition. The effects of other less severe chronic airway disorders on cognition remain to be clarified. This study aimed to measure and compare cognitive deterioration in subjects with COPD, subjects with chronic non-obstructive bronchitis (CNOB), and asymptomatic smokers (AS), and to relate the corresponding prevalence to several demographic and clinical variables and to normal reference values. METHODS: Four hundred and two subjects (COPD n=229, CNOB n=127, and AS n=46) of comparable age were included in the study. Cognitive impairment was assessed using the Mini Mental Status test, the Clock Drawing test, and the Trail Making test A and B. RESULTS: The extent and prevalence of cognitive deterioration was greater in COPD subjects, followed by CNOB subjects and AS (P<0.001). The Medical Research Council and COPD Assessment test scores, forced expiratory volume in the first second predicted, and arterial partial pressure of O2 and of CO2 were related to the extent and the prevalence of cognitive deterioration. COPD subjects, CNOB subjects, and AS aged 40-69 years showed the greatest cognitive impairment (P<0.01 compared to normal values). This was particularly clear in COPD subjects. CONCLUSION: Cognitive impairment may start at the early stages of chronic airway damage and progress with a worsening of the respiratory condition. Indeed, the greatest cognitive deterioration was seen in COPD subjects. Cognition impairment may contribute to explaining the insufficient adherence to therapeutic plans and strategies, and the increasing social costs in respiratory subjects.

Omalizumab management beyond clinical trials: the added value of a network model.

BACKGROUND: Omalizumab is effective and safe in severe allergic asthma. Few data are available about its impact on lung function and on asthma comorbidities, long-term follow-up of treated patients, adherence, non-responders profile, and optimal treatment duration. OBJECTIVE: We aimed at evaluating omalizumab-related clinical outcomes and unmet needs in a real-life setting. METHODS: We created a collaborative network (NEONet - North East Omalizumab Network) involving 9 Allergy and Respiratory referral centres for severe asthma placed in the North-East of Italy. Patients' data were entered into a common study database shared by all the participating physicians. A preliminary retrospective analysis was performed. RESULTS: Patients come from a common well-defined geographical and environmental district providing a homogeneous population sample. A moderate but statistically significant improvement of the FEV1, and an increasing proportion of exacerbations-free patients were observed since the treatment start. These findings were independent of the baseline severity of bronchial obstruction. A positive impact of omalizumab on rhinitis in patients with both asthma and rhinitis was detected. Moreover the efficacy of omalizumab on asthma seemed not to be affected by the baseline severity of rhinitis. CONCLUSION: Our retrospective analysis represents a preliminary report from the NEONet activity. It confirmed omalizumab efficacy and provided some new insights about its impact on lung function and on comorbid rhinitis. The network approach, under a prospective view, allows creating a large uniform database, by means of a standardized shared tool for data collecting, and joining a multidisciplinary expertise.

Prevalence of tracheobronchomalacia and excessive dynamic airway collapse in bronchial asthma of different severity.

BACKGROUND: Tracheobronchomalacia (TBM) is a pathologic condition in which softening of tracheal and bronchial cartilage causes the dynamic narrowing of transverse or sagittal diameters of tracheobronchial lumen; an excessive dynamic airway collapse (EDAC) may also be associated, with a substantial invagination of the posterior membrane of trachebronchial tree.The aim of this study was to assess the prevalence of both TBM and EDAC in a population of asthmatics with different degrees of disease severity compared to a reference group of subjects without any bronchial obstruction. METHODS: A cohort of 202 asthmatics was investigated by means of a dynamic flexible videobronchoscopy: 74 mild persistent (MPA - age 18-68 ys; 35 males; mean FEV1 = 88.6% pred. ± 8.3 sd); 63 moderate (MA - age 21-71 ys; 30 males; mean FEV1 = 71.3% pred. ± 9.1 sd), 65 severe asthmatics (SA - age 33-70 ys; 25 males; mean FEV1 = 48.5% pred. ± 7.6 sd), and 62 non obstructed subjects (NO - age 18-71 ys; 38 males; mean FEV1 98.6% pred. ± 2.7 sd). TBM and EDAC were classified according to FEMOS classification. RESULTS: TBM and EDAC were observed in only 1/62 subjects (both 1.61%) of NO group, while their prevalence was 2.70% and 6.75% in MPA group; 7.93% and 19.04% in MA group; 18.46% and 69.23% in SA group, respectively. The crude prevalence of thyroid disorders in the population was 12.9%. In particular, the prevalence of thyroid disorders was significantly higher in females than in men, but 54-fold higher in females than in men in the presence of EDAC. CONCLUSIONS: 1) The prevalence of both TBM and EDAC is directly related to age, gender (females), and asthma severity; 2) EDAC is much more frequent than TBM in all asthma patients; 3) both tracheal abnormalities proved to be more represented in asthmatics with thyroid disorders, and particularly in female asthmatics with EDAC.

A 36-month study on the cost/utility of add-on omalizumab in persistent difficult-to-treat atopic asthma in Italy.

OBJECTIVE: Omalizumab is a biological treatment for difficult-to-treat allergic asthma. Its mechanism of action relies on impeding the binding of immunoglobulin E (IgE) to specific cellular receptors, thus blocking the inflammatory cascade. At present, no long-term data are available on its cost/effectiveness. The aim of this study is to assess long-term clinical outcomes and to measure the cost/utility of long-term omalizumab use in difficult-to-treat allergic asthmatics. METHODS: The clinical, economic, and quality-of-life (QoL) outcomes of 36-month add-on omalizumab therapy were compared to equivalent outcomes for the year before the therapy's introduction in a cohort (n = 16) of adults with severe uncontrolled atopic asthma on chronic high-dose antiasthma treatments. The variables considered were lung function, IgE levels, health status, Asthma Control Test (ACT) score, QoL (St. George Questionnaire), general practitioner (GP) and specialist visits, number and duration of hospitalizations, emergency room admission, and pharmacological treatment (both dose and duration). Derived calculated indicators were changes in health-related QoL, total healthcare costs, and incremental cost/utility. Data from the two periods were tested for statistically significant differences according to Student's t test and p < .05 was accepted. RESULTS: Add-on omalizumab significantly and progressively improved asthma control and patient health-related QoL. Symptomatic drug and hospital care costs for these patients dropped significantly. A €450 increase in overall monthly costs was observed; however, when health benefits were considered, this cost increase translated into an incremental cost/utility ratio of €23,880 per quality-adjusted life year gained, which is quite a favorable and convenient figure in terms of the willingness to pay for health benefits in industrialized countries. CONCLUSIONS: The 36-month add-on omalizumab therapy persistently improved all clinical outcomes in difficult-to-treat asthmatic patients. Costs were also optimized and related to the extent of long-term health benefits achieved.

Changes in blood hemoglobin and blood gases PaO2 and PaCO2 in severe COPD overa three-year telemonitored program of long-term oxygen treatment.

BACKGROUND: Information on the effects of long-term oxygen treatment (LTOT) on blood hemoglobin (Hb) in severe COPD are limited. The aim was to assess blood Hb values in severe COPD, and investigate the time-course of both Hb and blood gas changes during a 3-year telemetric LTOT. METHODS: A cohort of 132 severe COPD patients (94 males; 71.4 years ± 8.8 sd), newly admitted to the tele-LTOT program, was investigated. Subjects were divided according to their original blood Hb: group A: <13 g/dL; group B: ≥13 < 15 g/dL; group C: ≥ 5 < 16 g/dL; group D: ≥16 g/dL. Blood Hb (g/dL), PaO2 and PaCO2 (mmHg), SaO2 (%), and BMI were measured at LTOT admission (t0), and at least quarterly over three years (t1-t3). Wilcoxon test was used to compare t0 vs. t1 values; linear regression to assess a possible Hb-BMI relationship; ANOVA to compare changes in Hb time-courses over the 3 years. RESULTS: LTOT induced a systematic increase of PaO2, and changes were significant since the first year (from 52.1 mmHg ± 6.6sd to 65.1 mmHg ± 8.7 sd, p < 0.001). Changes in SaO2 were quite similar. Comparable and equally significant trends were seen in all subgroups (p < 0.001). PaCO2 dropped within the first year of LTOT (from 49.4 mmHg ± 9.1sd to 45.9 mmHg ±7.5 sd, p < 0.001): the t0-t1 comparison proved significant (p < 0.01) only in subgroups with the highest basal Hb, who showed a further PaCO2 decline over the remaining two years (p < 0.001). Hb tended to normalization during LTOT only in subgroups with basal Hb > 15 g/dl (ANOVA p < 0.001); anemic subjects (Hb < 13 g/dl) ameliorated not significantly in the same period (ANOVA = 0.5). Survival was independent of the original blood Hb. Anemia and polyglobulia are differently prevalent in COPD, the latter being the most represented in our cohort. LTOT affected both conditions, but to a different extent and according to different time-courses. The most striking Hb improvement was in polyglobulic patients in whom also PaO2, PaCO2 and SaO2 dramatically improved. In anemic subjects effects were smaller and slower, oxygenation being equally ameliorated by LTOT. CONCLUSIONS: LTOT effects on Hb and PaCO2 are regulated by an Hb-dependent gradient which seems independent of the original impairment of blood gases and of effects on oxygenation.

Changes in total IgE plasma concentration measured at the third month during anti-IgE treatment predict future exacerbation rates in difficult-to-treat atopic asthma: a pilot study.

UNLABELLED: In severe, difficult-to-treat atopic asthma with sensitization to perennial allergens, monoclonal antibodies directed against immunoglobulin E (IgE) are recognized to be clinically effective. Omalizumab, a recombinant monoclonal antibody, selectively binds to the high-affinity C-epsilon 3 site of human IgE and inhibits the inflammatory cascade in response to antigenic stimuli. Currently, no indicator is available for predicting patients' responsiveness to long-term omalizumab treatment. This study aims to assess the relationship between early changes in plasma IgE concentration and major outcome variables over a 12-month course of omalizumab. METHODS: Twenty-three nonsmoking, severe asthmatics (14 females; mean age 47.3 years ± 12.0 SD; mean BMI 25.8 kg/m(2) ± 9.6 SD) sensitized to perennial allergens and unresponsive to high doses of common therapies were evaluated during a 12-month period of omalizumab treatment. Variables included total IgE plasma concentrations, Forced Expiratory Volume 1 second (FEV(1)) symptom complaints (Asthma Control Test (ACT) score), number of emergency visits, hospitalizations, and exacerbations. The Wilcoxon signed-rank test was used to compare changes observed after the 1-year omalizumab treatment versus baseline. Statistical modelization was used to determine possible relationships between changes in outcomes after 12 months and early changes in plasma IgE (after 3 months of treatment). RESULTS: The number of emergency visits, hospitalizations, and exacerbations decreased (p < .004, p < .001, and p < .001, respectively) over the 12-months. In contrast, FEV(1) and ACT score substantially increased (both p < .001); the ACT score reaching maximum after only 3 months. The S model showed the best fit and proved the strict relationship between the increase in IgE after 3 months and the exacerbation rate over the 1-year survey (threshold value of ≥250 IU/ml, p < .001). The improvement in FEV(1) was independent of the increase in IgE. CONCLUSIONS: When confirmed on a larger population, early changes in IgE may be used as a predictor of future responders to omalizumab in terms of exacerbation rate, thus minimizing the economic burden of anti-IgE therapy.

The impact of LABA+ICS fixed combinations on morbidity and economic burden of COPD in Italy: a six-year observational study.

BACKGROUND: In Italy, chronic obstructive pulmonary disease (COPD) has progressively received increasing attention in the last decade, and its impact has been investigated extensively in both clinical and pharmacoeconomic terms. METHODS: In 2004, the national health authorities stated the appropriateness of long-acting ß(2) agonists (LABA) and inhaled corticosteroids (ICS) fixed combinations for treating COPD, even though this pharmaceutical option was limited to the severe and very severe stages of the disease (forced expiratory volume in one second [FEV(1)] <50% predicted). The effectiveness in primary care of this official recommendation has been investigated in 1125 COPD patients together with the appropriateness of the therapeutic approach to the disease. RESULTS: and conclusions: Clinical and economic outcomes were monitored over the 3 years before (2001-2003) and the 3 years following this recommendation (2004-2006), and statistically compared (t-test). In general, the overall impact of COPD changed progressively after the pronunciation of the public health authorities. In particular, since the point when LABA/ICS fixed combinations were officially recommended, both morbidity of COPD and the corresponding consumption of healthcare resources have progressively lowered. Moreover, the appropriateness of the pharmaceutical approach increased in the same period, thus emphasizing the importance of the optimization of therapeutic strategies in reducing the long-term impact of the disease.

A MCh test pre-post esophageal acidification in detecting GER-related asthma.

The direct effect of gastro-esophageal reflux (GER) on lung function is still debated. Objective. To investigate the role of esophageal acidification in affecting airway response to MCh in GER-related versus atopic asthmatics and to assess specificity and sensitivity of events. Subjects. A total of 56 never-smoking, mild asthmatics: 27 non-atopic asthmatics and acid GER (GER+ve) and 29 atopic asthmatics without any GER (GER-ve). Methods. Each subject performed an MCh challenge in baseline (MCh(b)), and 30 minutes after an acid drink (125 mL at pH = 2; MCh(ac)), one day apart. PD(20)FEV(1) MCh(b) and MCh(ac) were compared by estimating the area under the ROC curve (AU-ROC). Results. GER+ve and GER-ve subjects (well matched in baseline) had a different duration of esophageal acid contact (24-hour monitoring; pH-24h AU(4)), and PD(20)FEV(1) MCh(ac) (both p < 0.001). AU-ROC was 86.3% (76% to 97%, 95%CI). Sensitivity and specificity of changes were 82.8% (72.9% to 92.7%, 95%CI) and 85.2% (75.9% to 94.5%, 95%CI), respectively. The difference in MCh threshold that maximized both the sensitivity and specificity level was 100 mu g. Conclusions. The esophageal acidification identified GER-related asthma with a good level of both sensitivity and specificity by enhancing the MCh response only in the presence of acid GER. Data are supporting the effectiveness of this procedure for clinical purposes.

Tobramycin Nebulizer Solution in severe COPD patients colonized with Pseudomonas aeruginosa: effects on bronchial inflammation.

INTRODUCTION: Airway colonization with Pseudomonas aeruginosa is frequent in severe chronic obstructive pulmonary disease (COPD) and may lead to progressive inflammatory damage. Inhaled Tobramycin Nebulizer Solution (TNS; a preservative-free formulation) is an effective therapy in chronic P aeruginosa infection in cystic fibrosis and bronchiectasis. In this study we aimed to investigate the effects of a TNS short course on inflammatory markers in bronchial secretions from multiresistant P aeruginosa-colonized patients with severe COPD. To the authors' knowledge, this is the first study to examine this in cases of severe COPD. METHODS: Thirteen COPD patients (GOLD criteria 3-4; mean age 72.7+/- 8 years; mean basal forced expiratory volume in 1 second (FEV(1)) 34.8%+/-8.1%; mean FEV(1)/forced vital capacity 0.6+/-0.1) were enrolled. All patients were colonized with P aeruginosa and resistant to oral/intravenous specific antibiotics. Eosinophilic cationic protein (ECP), interleukin-1 beta (IL-1beta), interleukin-8 (IL-8), tumor necrosis factor alfa (TNF-alpha), and cell counts were measured in spontaneous secretions before and after a 2-week TNS course (300 mg twice daily). RESULTS: The TNS course induced a significant reduction in IL-1beta (P<0.03), IL-8 (P<0.02), ECP (P<0.01) concentrations, and in eosinophil count (P<0.01). TNF-alpha levels, and neutrophil and lymphocyte counts were not significantly affected. The second week of treatment proved crucial in terms of efficacy. P aeruginosa density was lowered after 6 months; severe acute exacerbations were reduced by 42%. CONCLUSION: TNS reduced the inflammatory impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with severe COPD. A therapeutic role for TNS can be strongly suggested in these particular conditions.

Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD.

BACKGROUND: Oxidative stress is presumed to impair beta-adenoceptor function and airway patency. Erdosteine (E), a mucomodulatory compound, has shown important antioxidant properties. METHODS: The objective was to assess the effect of antioxidant interventions on short-term airway response to salbutamol in non-reversible mild-to-moderate COPD patients. Thirty COPD patients (GOLD class 1-2), current smoker (>or=10 pack/year), randomly received E 300 mg, N-acetylcysteine (NAC) 600 mg, or placebo, twice daily for ten days. Reversibility to salbutamol 200 microg was tested in baseline, after four and ten days of each treatment. ROS and 8-isoprostane blood levels were measured on the same days. Between-treatment comparison was performed by ANOVA and t-test or Wilcoxon test, and p<0.05 assumed. E enhanced FEV1 reversibility after four and ten days significantly (+5.1% and +5.0%; both p<0.01 vs. placebo), while NAC only showed a transient effect at day 4 (+3.0%, p<0.05), but not at day 10 (+1.3%, p = ns). RESULTS: E and NAC caused significant drops in ROS blood levels after four and ten days (p<0.001 and p<0.0001 vs. placebo). In contrast to NAC, E lowered 8-isoprostane levels substantially for ten days (p = 0.017 and p = 0.0004 vs. placebo, respectively). Only E restored significantly short-term reversibility in COPD patients previously unresponsive to beta(2)-adrenergics. CONCLUSIONS: This effect seems more related to the peculiar protection against lipid peroxidation rather than to the scavenging activity, which proves equal to that of NAC. E provides a sort of indirect bronchodilation through 're-sensitisation' of beta( 2)-adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.