Symptom versus exacerbation control: an evolution in GINA guidelines?

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

Chronic obstructive pulmonary disease: moving from symptom relief to mortality reduction.

Chronic obstructive pulmonary disease (COPD) has a 3-year mortality rate up to 37%, 2-6 times higher than the general population. We present evidence supporting pharmacological therapies to improve patient life expectancy, focusing on inhaled corticosteroids (ICSs) combined with long-acting bronchodilators (LABDs). A reduction in 3-year all-cause mortality (ACM) has been shown in patients with severe COPD treated with fluticasone propionate (an ICS) and salmeterol [long-acting beta-agonist (LABA)], compared with placebo. An observational study of elderly patients with severe COPD and multiple comorbidities suggested ICS+LABD reduce ACM compared with LABD monotherapy. Patients with symptomatic COPD at risk of exacerbations saw a mortality benefit with the ICS/long-acting muscarinic antagonist (LAMA)/LABA combinations fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) versus UMEC/VI or GLY/FOR (LAMA/LABA combinations) in the IMPACT and ETHOS trials, respectively. Reduced risk of mortality may be due to modulation of airway inflammation, thereby reducing activation of proinflammatory mediators in the peripheral circulation. Importantly, estimated annual risk reduction for ACM with ICS/LAMA/LABA combinations in patients with COPD is of the same order of magnitude as for statins (patients with coronary disease) and angiotensin-converting enzyme inhibitors (patients with vascular disease). Based on the current data, the pharmacological treatment of COPD appears not only able to improve symptoms and reduce the frequency of exacerbations but is also very promising in improving patient prognosis in the long term.

Open triple therapy for chronic obstructive pulmonary disease: Patterns of prescription, exacerbations and healthcare costs from a large Italian claims database.

BACKGROUND: The combination of two long acting bronchodilators with an inhaled corticosteroid, known as Triple Therapy (TT), is a usual clinical practice for patients affected by chronic obstructive pulmonary disease (COPD). This analysis aimed to identify subjects with COPD treated with extemporaneous combination of ICS/LABA and LAMA (namely open TT) and to describe the pharmacological strategy, the spirometry use, the exacerbations occurrence and the costs, in the perspective of the Italian National Health System (NHS). METHODS: Through record linkage of administrative data (ReS database) of about 12 million inhabitants in 2014, a cohort of patients aged ≥45, without asthma and treated with open TT (index date) was selected. Specific drugs, oxygen supply and exacerbations were described in one year before the index date, while spirometry tests over two years before the index date. All these resources utilization, the persistence to the open TT, and integrated costs of the above healthcare services were analysed for 1-year follow-up. RESULTS: In 2014, 10,352 patients (mean age 74 ± 9; males 66.0%) with COPD and treated with open TT were identified (prevalence 160.6 per 100,000 inhabitants aged ≥45). During the previous year, the 44.0% of this cohort was already treated with open TT, 7.0% did not received any drugs for obstructive airway diseases, 11.1% needed home oxygen therapy, and 28.7% experienced at least an exacerbation. In the follow-up year, the 37.5% of the cohort was found persistent to the open TT, 17.0% needed oxygen therapy, and the 30.9% underwent an exacerbation. Spirometry was performed on 45.7% of patients in the two previous years, while on 33.3% in the subsequent year. In the follow-up, on average, every patient of the cohort costed to the NHS €5,295: 48.2% for hospitalizations, 41.2% for drugs and 10.6% for outpatient services. CONCLUSIONS: This large observational study based on claims data reliably identified subjects with COPD treated with open TT and their burden on the NHS. Moreover, it could describe the real clinical management of the open TT, before the marketing of the fixed one. These findings are useful for health policymakers in order to promote the appropriate utilization of both currently marketed and future therapies.

A Panel Study on Lung Function and Bronchial Inflammation among Children Exposed to Ambient SO2 from an Oil Refinery.

To determine the acute effects on respiratory function of children exposed to sulphur dioxide (SO2), we conducted two population-based longitudinal investigations near a major oil refinery. We enrolled 233 children, age 8⁻14, in Sarroch (Italy). The first study entailed five monthly spirometric visits (Panel 5). In a subgroup, children positive for history of respiratory symptoms were tested weekly (20 times) with spirometry and fractional exhaled nitric oxide (FeNO) measurement (Panel 20). Baseline questionnaires and daily diaries were recorded. SO2, NO2, PM10 and O3 were measured by monitoring stations. Multiple regression models were fitted. Using a multipollutant model, we found that a 10 µg/m³ SO2 increase at lag0⁻2 days determined a percent variation (PV) of -3.37 (90% confidence interval, CI: -5.39; -1.30) for forced expiratory volume after one second (FEV1) in Panel 5 and a PV = -3.51 (90% CI: -4.77; -2.23) in Panel 20. We found a strong dose-response relation: 1-h SO2 peaks >200 µg/m³ at lag2 days = FEV1 PV -2.49. For FeNO, we found a PV = 38.12 (90% CI: 12.88; 69.01) for each 10 µg/m³ SO2 increase at 8-h time lag and a strong dose-response relation. Exposure to SO2 is strongly associated with reduction of lung function and an increase in airway inflammation. This new evidence of harmful effects of SO2 peaks should induce regulatory intervention.

[Validation of algorithms for the identification of subjects with chronic disease using health information systems]. / Validazione di algoritmi per l'identificazione di persone con patologia cronica attraverso i dati dei sistemi informativi.

OBJECTIVES: to test the validity of algorithms to identify diabetes, chronic obstructive pulmonary disease (COPD), hypertension, and hypothyroidism from routinely collected health data using information from self-reported diagnosis and laboratory or functional test. SETTING AND PARTICIPANTS: clinical or self-reported diagnosis from three surveys conducted in Lazio Region (Central Italy) between year 2010 and 2014 were assumed as gold standard and compared to the results of the algorithms application to administrative data. MAIN OUTCOME MEASURES: prevalence resulted from administrative data and from information available in the surveys were compared. Sensitivity, specificity, positive predictive value, and positive likelihood ratio of algorithms with respect to self-reported diagnosis, laboratory or functional test, assumed as gold standards, were calculated. RESULTS: we analyzed data of 7,318 subjects (1,545 for diabetes, 1,783 for COPD, 2,448 for hypertension, and 1,542 for hypothyroidism). For hypertension and hypothyroidism, we observed a higher prevalence from laboratory or functional test compared to self-reported diagnosis (54.5% vs. 44.9% and 7.5% vs. 1.5%). Sensitivity of administrative data with respect to self-reported diagnosis resulted 90.9%, 38.5%, 88.3%, and 47.8%, respectively, for diabetes, COPD, hypertension, and hypothyroidism. Respectively, specificity was 97.4%, 91.7%, 84.8% and 91.8%; positive predictive value was 70,9%, 38.1%, 82.6% and 8.1%. All values of positive likelihood ratio resulted moderate (about 5), with exception of the diabetes algorithm and the disease-specific payment exemptions register for hypertension (respectively 35.5 and 17.4). CONCLUSION: hypertension and hypothyroidism resulted markedly underdiagnosed from self-reported data. Case identification algorithms are highly specific, allowing their utilization for selection of cohort of subject affected by chronic diseases. The sub-optimal sensitivity observed for COPD and hypothyroidism could limit the utilization of the algorithms for prevalence estimation.

Indacaterol/Glycopyrronium in the Treatment of Severe Respiratory Failure: Marked Improvement of Respiratory Failure in a Few Weeks - A Case Report.

Chronic obstructive pulmonary disease is a highly prevalent disease, especially in the aging population, associated with several functional disabilities and a high economic burden. Dual bronchodilation with prefixed associations of long-acting ß2-agonists and long-acting muscarinic antagonist have a significant role in the management of this condition. The newer combination, indacaterol/glycopyrronium, is useful as a once-a-day therapy and has proven superior to other treatment strategies including inhaled corticosteroids for improving symptoms and clinical condition with a very rapid effect. We report our experience with a patient suffering from severe respiratory failure who improved significantly when the indacaterol/glycopyrronium combination was added to his therapy.

Inhaled Corticosteroid Use in Chronic Obstructive Pulmonary Disease and Risk of Pneumonia: A Nested Case-Control Population-based Study in Lazio (Italy)-The OUTPUL Study.

Inhaled corticosteroid (ICS) use in chronic obstructive pulmonary disease (COPD) patients is associated with a reduction of exacerbations and a potential risk of pneumonia. The objective was to determine if ICS use, with or without long-acting ß2-agonist, increases pneumonia risk in COPD patients. A cohort study was performed using linked hospital and drug prescription databases in the Lazio region. Patients (45+) discharged with COPD in 2006-2009 were enrolled and followed from cohort entry until first admission for pneumonia, death or study end, 31 December, 2012. A nested case-control approach was used to estimate the rate ratio (RR) associated with current or past use of ICS adjusted for age, gender, number of exacerbations in the previous year and co-morbidities. Current users were defined as patients with their last ICS prescribed in the 60 days prior to the event. Past users were those with the last prescription between 61 and 365 days before the event. Current use was classified into three levels (high, medium, low) according to the medication possession ratio. Among the cohort of 19288 patients, 3141 had an event of pneumonia (incidence rate for current use 87/1000py, past use 32/1000py). After adjustment, patients with current use were 2.29 (95% confidence interval [CI]: 1.99-2.63) times more likely to be hospitalised for pneumonia with respect to no use; for past use RR was 1.23 (95% CI: 1.07-1.42). For older patients (80+), the rate was higher than that for younger patients. ICS use was associated with an excess risk of pneumonia. The effect was greatest for higher doses and in the very elderly.

The impact of adherence to inhaled drugs on 5-year survival in COPD patients: a time dependent approach.

PURPOSE: Whether inhaled medications improve long-term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5-year survival in COPD. METHODS: A population-based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006-2009 were enrolled. Inhaled drug daily use during 5-year follow-up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time-dependent exposure were identified: (i) long-acting ß2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio-demographic, comorbidities, drug use) and time-dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed. RESULTS: A total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow-up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43-1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79-0.99). CONCLUSIONS: These findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate-severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Can the New Global Lung Initiative Equations Better Stratify the Risk of Death in Elderly People with Chronic Obstructive Pulmonary Disease?

BACKGROUND: The forced expiratory volume in the first second (FEV1) is commonly expressed as percentage of its value predicted by equations. The most commonly used equations are poorly applicable to elderly people. Recently, a set of equations (Global Lung Initiative, GLI) has been released that is expected to be more appropriate in this population. OBJECTIVES: We evaluated the agreement of the GLI, European Respiratory Society (ERS), and National Health and Nutrition Examination Survey (NHANES) equations for prediction of FEV1 and compared their discriminative capacity with respect to mortality, taking as reference the prediction equation developed in the population from which our sample was drawn (SARA). METHODS: We studied 264 patients with chronic obstructive pulmonary disease aged ≥70 years. Agreement was evaluated using the Bland-Altman method, discriminative capacity using incidence rate ratios for mortality calculated across quartiles of each measure. RESULTS: The mean age of the sample was 75.8 years (72.7% men). In women, the mean FEV1ERS/FEV1SARA, FEV1NHANES/ FEV1SARA, and FEV1GLI/FEV1SARA were 0.81, 0.91, and 0.966, respectively. The corresponding values in men were 0.959, 0.963, and 1.02, respectively. The overall discriminative capacity with respect to death was equally poor for all equations. CONCLUSION: The GLI equations for predicting FEV1 provide similar estimates compared to an equation developed in a healthy subset of the population in which they are applied, and higher values compared to the ERS equation, especially in women. However, the use of the GLI equation does not improve the stratification of the risk of mortality in elderly people compared to ERS or NHANES equations.

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long-Acting ß2 -Agonists and Inhaled Corticosteroids: The OUTPUL Study.

Combined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long-acting ß2 agonists (LABA) and/or inhaled corticosteroids (ICS). This new-user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention-to-treat and as-treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score-adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention-to-treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89-1.16), 0.92 (95%CI 0.76-1.12), and 1.08 (95%CI 0.91-1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48-0.98 in intention-to-treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment.

One-year mortality associated with COPD treatment: a comparison of tiotropium and long-acting beta2-agonists in three Italian regions: results from the OUTPUL study.

PURPOSE: Long-acting bronchodilators, i.e. beta-2-agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one-year mortality associated to treatment with tiotropium versus LABA. METHODS: A population-based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006-2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used 'intention to treat' (ITT) and 'as treated' (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group. RESULTS: Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person-years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94-1.20) at the ITT analysis and 1.00 (95%CI: 0.93-1.08) at the AT analysis. Results were robust in sensitivity analysis. CONCLUSIONS: In this real-world study use of tiotropium was not associated with an increased risk of one-year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

The Effect on Total Mortality of Adding Inhaled Corticosteroids to Long-Acting Bronchodilators for COPD: A Real Practice Analysis in Italy.

PURPOSE: Chronic therapy with long-acting bronchodilators (LB) is recommended to treat moderate-to-severe COPD. Although the benefits of adding inhaled corticosteroid (ICS) to LB are still unclear, patients who experience repeated exacerbations are suggested to add ICS to their LB treatment. The objective of this study is to analyze whether adding ICS to LB therapy reduces mortality. METHODS: We identified a cohort of patients discharged from hospital with COPD diagnosis between 2006 and 2009. The first prescription for LB or ICS following discharge was defined as the index prescription. Only new users were included (no use of any study drug in the 6 months before treatment). A 4-day time window was used to classify patients into "LB alone" or "LB plus ICS" initiators. We used propensity score to balance the study groups. Sensitivity analyses were performed in patients with recent out-of-hospital exacerbations. RESULTS: Among the 18615 adults enrolled, 12207 initiated "LB plus ICS" therapy and 6408 "LB alone." Crude mortality rates were 110 and 143 cases per 1000 person-years in the "LB plus ICS" and "LB alone" groups, respectively. The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.72-0.97; p-value: 0.024). When analyzing patients with recent out-of-hospital exacerbations, the benefit of the combination therapy was more pronounced, HR = 0.63 (95% CI: 0.44-0.90; p-value: 0.012). DISCUSSION: Our findings showed a beneficial effect on mortality of adding inhaled corticosteroids to long-acting bronchodilators. The advantage was much more pronounced in patients with frequent exacerbations.

Opening of a respiratory intermediate care unit in a general hospital: impact on mortality and other outcomes.

BACKGROUND: Respiratory intermediate care units (RICUs) are specialized areas aimed at optimizing the cost-benefit ratio of care. No data exist about the impact of opening a RICU on hospital outcomes. OBJECTIVES: We wondered if opening a RICU may improve the outcomes of patients with acute respiratory failure (ARF), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or community-acquired pneumonia (CAP). METHODS: We analyzed the discharge abstracts of 2,372 admissions to the RICU and internal medicine units (IMUs) for ARF, AECOPD, and CAP. The IMUs at the Hospital of Trieste comprise emergency and internal wards. In order to investigate the determinants of outcomes, a matched case-control study was performed using clinical records. RESULTS: The in-hospital mortality rate was lower in the RICU vs. IMUs (5.4 vs. 19.1%, p = 0.0001). Statistical differences did not change when comparing the RICU with the emergency and internal wards. After adjusting for potential confounders, the risk of death for patients with CAP, AECOPD, or ARF was significantly higher in the IMUs than in the RICU (OR 6.90, 3.19, and 6.7, respectively, p < 0.04). Both the frequency of transfer to the ICU (6 vs. 12%, p = 0.0001, OR 0.38) and the hospital stay (9.3 vs. 12.1 days, p = 0.0001) were reduced in patients admitted to the RICU compared to those admitted to non-RICUs. Significant differences were found in care management concerning chest physiotherapy, mechanical ventilation, antibiotics, and corticosteroids. CONCLUSIONS: The opening of a RICU may be advantageous to reduce in-hospital mortality, the need for ICU admission, and the hospital stay of patients with AECOPD, CAP, and ARF. Better use of care resources contributed to better patient management in the RICU.

Lactobacillus reuteri ATCC55730 in cystic fibrosis.

OBJECTIVES: The aim of this study was to evaluate in patients with cystic fibrosis (CF) the effect of Lactobacillus reuteri (LR) on the rate of respiratory exacerbations and of the infections of both upper respiratory and gastrointestinal tracts. METHODS: Prospective randomized, double-blind, placebo-controlled study enrolling 61 patients with CF with mild-to-moderate lung disease at the Regional Center for CF of the Department of Pediatrics, University of Rome "La Sapienza." All of the patients were not hospital inpatients at the time of the enrollment. Inclusion criteria were forced expiratory volume in the first second (FEV1) >70% predicted; no inhaled or systemic steroids, no anti-inflammatory drugs, antileukotrienes, and mast cell membrane stabilizers; and no serious organ involvement. Exclusion criteria were a history of pulmonary exacerbation or upper respiratory infection in the previous 2 months; changes in medications in the last 2 months; a history of hemoptysis in the last 2 months; and colonization with Burkholderia cepacia or mycobacteria. Patients were randomly assigned to receive LR (30 patients) in 5 drops per day (10(10) colony-forming units) or placebo (31 patients) for 6 months. Main outcomes were number of episodes of pulmonary exacerbations and hospital admissions for pulmonary exacerbations, number of gastrointestinal and upper respiratory tract infections. FEV1, fecal calprotectin, and cytokine profile in induced sputum and plasma were assessed at baseline and at the end of the trial. RESULTS: Pulmonary exacerbations were significantly reduced in the LR group compared with the placebo group (P<0.01; odds ratio 0.06 [95% confidence interval {CI} 0-0.40]; number needed to treat 3 [95% CI 2-7]). Similarly, the number of upper respiratory tract infections (in our series only otitis) was significantly reduced in the LR group compared with the placebo group (P<0.05; odds ratio 0.14 [95% CI 0-0.96]; number needed to treat 6 [95% CI 3-102]). The 2 groups did not differ statistically in the mean number and duration of hospitalizations for pulmonary exacerbations and gastrointestinal infections. There was no significant statistical difference in the mean delta value of FEV1, fecal calprotectin concentration, and tested cytokines (tumor necrosis factor-α and interleukin-8) between the 2 groups. CONCLUSIONS: LR reduces pulmonary exacerbations and upper respiratory tract infections in patients with CF with mild-to-moderate lung disease. LR administration may have a beneficial effect on the disease course of CF.

Use patterns of long-acting bronchodilators in routine COPD care: the OUTPUL study.

BACKGROUND: COPD is the fourth leading cause of death in the world. In the case of exacerbations or persistent symptoms, regular treatment with long-acting bronchodilators is recommended to control the symptoms, reduce exacerbations and improve health status. Objectives. To describe patterns of drug utilization among patients diagnosed with COPD, to measure continuity with long-acting bronchodilators, to identify determinants of not receiving long-acting therapy continuously. METHODS: We identified a cohort of patients discharged from hospital with diagnosis of COPD between 2006 and 2008. Patients were observed for a two-year follow-up period, starting from the day of discharge. Follow-up was segmented in six-month periods, in order to dynamically evaluate prescription patterns of Long-Acting Beta-Agonists (LABA), tiotropium, and inhaled corticosteroids. Patients with prescriptions for LABA and/or tiotropium in each of the six-month periods were defined as "continuously treated with long-acting bronchodilators." The degree of drug treatment coverage was measured through the Medication Possession Ratio (MPR). Logistic regression was performed to identify determinants of not receiving long-acting bronchodilators continuously. RESULTS: A total of 11,452 patients diagnosed with COPD were enrolled. Only 34.8% received long-acting bronchodilators continuously. The MPR was greater than 75% in 19.6% of cases. Among the determinants of not receiving long-acting bronchodilators continuously, older age and co-morbidities played an important role. CONCLUSIONS: In clinical practice, the COPD pharmacotherapy is not consistent with clinical guidelines. Medical education is needed to disseminate evidence-based prescribing patterns for COPD, and to raise awareness among physicians and patients on the health benefits of an appropriate pharmacological treatment.

Prevalence of risk factors for venous thromboembolism in the Italian population: results of a cross-sectional study from the Master Registry.

The prevalence of major risk factors for VTE may differ according to age, gender and clinical presentation. We tested this hypothesis in a large Italian VTE population. MASTER is a multicenter registry aimed to prospectively collect information on a large cohort of patients with acute VTE. The presence of major risk factors was captured by an electronic data network in consecutive patients with objectively confirmed acute VTE. We enrolled 2,119 patients (49.8% men) of whom 424 (20%) <40 years, 529 (25%) between 41 and 60 years, 943 (44.5%) between 61 and 80 years, and 223 (10.5%) >80 years. The prevalence of known risk factors in the four age groups is 63.9, 52.6, 54.6, and 58.3%, respectively (p = 0.002). Immobilization and severe medical disorders are more commonly associated with VTE in patients >80 years, trauma is significantly more common in patients <40 years than in older patient groups. The prevalence of unprovoked events is the highest in patients 41-60 years, and lowest in patients less than 40 years. After logistic regression analysis, patients with pulmonary embolism are more likely to have known risk factors for VTE than patients with deep vein thrombosis at presentation (p = 0.0021), and women are less likely than men to have an unprovoked VTE (p < 0.0001). In conclusion, a substantial proportion of VTE events remain classified as unprovoked. Unprovoked events are more common in middle aged patients, in men, and in patients presenting with deep vein thrombosis.

Long-term death and recurrence in patients with acute venous thromboembolism: the MASTER registry.

BACKGROUND: The long-term clinical outcome of VTE has been essentially assessed in cohorts of selected patients. The aim of this multicenter registry was to prospectively assess the long-term clinical outcome in a cohort of unselected patients with objectively confirmed acute VTE. MATERIALS AND METHODS: Death and VTE recurrence at 24 months were the main study outcomes. Univariate and multivariate survival analyses were performed according to the Kaplan-Meyer and Cox proportional hazard model, respectively. RESULTS: 2119 patients with acute VTE were included in the registry: 1541 (72.7%) with deep vein thrombosis, 206 (9.7%) with pulmonary embolism and 372 (17.6%) with both. Information about death was available in 2021 patients (95.4%) and about recurrence in 1988 patients (93.8%). 167 patients (4.55% patient-year) died during follow-up. After adjusting for age, cancer (Hazard ratio [HR]: 7.2; 95%CI 4.8-10.8), long-term heparin treatment (HR: 2.5; 95%CI 1.8-3.5), in-hospital management of VTE (HR: 2.0; 95%CI 1.3-3.0), and ileo-caval thrombosis (HR: 1.7; 95%CI 1.2-2.4) were found to be independent predictors of death. 124 (3.63% patient-year) patients had a VTE recurrence during follow-up. In-hospital management of VTE (HR: 1.8; 95%CI 1.2-2.9), male gender (HR: 1.7; 95%CI 1.2-2.4) were independent risk factors for recurrent VTE. Cancer (HR: 1.6; 95%CI 1.0-2.8) showed a trend for increased risk of VTE recurrence (p=0.056). The reported rate of major bleeding was 2.5%. CONCLUSIONS: In a large cohort of unselected VTE patients, cancer, ileo-caval thrombosis, long-term heparin treatment and in-hospital management were associated with increased mortality during long-term follow-up. In-hospital management, male gender were associated with an increased risk of VTE recurrence.

Asthma symptoms, lung function, and markers of oxidative stress and inflammation in children exposed to oil refinery pollution.

OBJECTIVES: Little is known about the effects of exposure to petroleum refinery emissions on respiratory health in children. We evaluated lung function and markers of inflammation and oxidative stress in children and adolescents with and without asthma or wheezing symptoms living in a petrochemical polluted area (Sarroch, Sardinia) versus a reference area (Burcei). METHODS: Parents of 275/300 6- to 14-year-old children living in Sarroch and parents of 214/323 children living in Burcei answered a questionnaire on respiratory symptoms and risk factors. Measurements of forced expiratory volume after 1 second (FEV(1)) and of forced expiratory flow rates at 25-75% of vital capacity (FEF(25-75)) were available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for fractional exhaled nitric oxide (FE(NO)) corresponding figures were 27 and 24 and 8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde-deoxyguanosine (MDA-dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively). Air pollutants were assessed during 3 weeks, starting 1 week before lung function, FE(NO), and MDA-dG measurements. Generalized linear models were used to estimate the effect of the area of residence adjusting for confounders. RESULTS: Weekly average concentrations of sulfur dioxide were 6.9-61.6 µg/m(3) in Sarroch versus 0.3-7.6 µg/m(3) in the rural area of Burcei; of nitrogen dioxide, 5.2-28.7 µg/m(3) versus 1.7-5.3 µg/m(3); and of benzene, 1.8-9.0 µg/m(3) versus 1.3-1.5 µg/m(3), respectively. Children living in Sarroch versus children living in the reference area showed an increase in wheezing symptoms {adjusted prevalence ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung function [variation in FEV(1)=-10.3% (90% CI=-15.0; -6.0%) and in FEF(25-75)=-12.9% (90% CI=-20.7; -4.3%)]; an increase in bronchial inflammation [variation in FE(NO)=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA-dG adducts of +83% (90% CI=22.9; 174.1%). CONCLUSIONS: Data from this small study are consistent with the role of environmental pollutants on lung function and inflammation.