1-year prospective real life monitoring of asthma control and quality of life in Italy.

OBJECTIVES: The study aimed at prospectively evaluating the evolution of asthma control in Italy, to evaluate the reasons for lack of asthma control, perceived quality of life (QoL) and association with level of asthma control, the impact of pharmacological treatment, the number of exacerbations and the healthcare resource consumption. METHODS: PRISMA (PRospectIve Study on asthMA control) was an observational study performed in asthmatic patients including a cross-sectional phase and a 12-month prospective phase. Asthma control was assessed with the Asthma Control Test™ (ACT) and QoL was evaluated with EuroQoL-5D questionnaire filled in and collected during 5 clinic visits together with all the other data. RESULTS: The prospective phase included 1017 patients with uncontrolled (55.7%) or partly controlled asthma (44.3%). Out of the 739 patients evaluable after 12 months, 22.2% achieved full asthma control (ACT score = 25) and 58.7% reached a good control (ACT score: 20-24). The improvement in asthma control was associated with improved QoL and reduced hospital visits. The main reasons for lack of asthma control were comorbidities, continued exposure to irritants/triggers and poor adherence to therapy. The frequency of exacerbations was lower in patients with controlled asthma.A fixed combination therapy with an inhaled corticosteroid and a long-acting ß2 agonist was reported by 77.0% of patients. A better asthma control and improved QoL were achieved with extrafine beclomethasone/formoterol compared to either budesonide/formoterol or fluticasone/salmeterol. CONCLUSIONS: An improvement in asthma control and QoL can be achieved during a 1-year monitoring in a real life setting. Extrafine beclomethasone/formoterol was associated with significant benefit in terms of asthma control and QoL compared to large-particles combinations.ClinicalTrials.gov number NCT01110460.

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan.

BACKGROUND: Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. METHODS: We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0-2 and lag 3-5 in both single and multi-pollutant models, adjusted for daily weather variables. RESULTS: An increase in ozone (O(3)) levels at lag 3-5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0-2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO(2)), CO, nitrate dioxide (NO(2)), and particulate matter (PM(10) and PM(2.5)). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0-2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association. CONCLUSIONS: Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

Hyaluronic acid : perspectives in lung diseases.

Hyaluronic acid (HA) is a non-sulphated glycosaminoglycan. It is a natural polymer characterised by a coiled linear chain in particularly well-hydrated configuration composed of repeating disaccaride units. In mammals, its molecular weight can be extremely wide, ranging from 20 to 4,000 kDa. High molecular mass forms are provided with anti-inflammatory properties. A unique characteristic of HA is hydration (up to 6,000 molecules water/molecule of HA) with a major role in the regulation of fluid balance in the interstitium, a fundamental activity on the amorphous colloidal matrix gluing connective cell and fibers, and many other biological functions including lubrication, solute transport and microcirculatory exchange. HA has been widely used in the treatment of eye, ear, joint and skin disorders; in the last 15 years HA has been also proposed successfully in the treatment of a number of lung diseases in vitro, experimental animals and humans. In particular, inhaled HA at relatively high molecular weight has been proven to prevent bronchoconstiction induced in asthmatics by direct and indirect challenges such as inhalation of methacholine, inhalation of ultrasonically nebulised distilled water, muscular exercise. More recently, in patients affected by chronic obstructive pulmonary diseases, we have demonstrated that repeated administrations of inhaled HA (daily, for 8 weeks) induce significant increase in bronchial patency as well as progressive lung deflation with decrease of residual volume. In conclusion there are elements that can let us state that is perhaps time to change the focus to connective tissue and extracellular matrix substances such as HA, in order to prevent and treat chronic lung diseases.

Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV(1), RV, PaO(2), and PaCO(2) were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV(1), PaO(2), the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.

Chlamydia pneumoniae and acute aortic syndrome: a call for a multi-institutional study.

Chlamydia Pneumoniae (CP) infection is strongly associated with coronary artery disease, as well as with atherosclerosis of the carotid and peripheral arteries. However, the role of CP in the pathogenesis of aortic disease remains controversial. Our present experience suggests no correlation between a current infection with C. pneumoniae and acute aortic dissection. Well-designed large prospective studies are needed in order to clarify the pathophysiologic role of CP infection in acute and chronic aortic disease.

Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice.

BACKGROUND: It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated. METHODS: In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21. RESULTS: We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-gamma (IFN-gamma) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-alpha (TNF-alpha) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness. CONCLUSION: Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD.

[Echocardiography and pulmonary arterial hypertension]. / Ecocardiografia ed ipertensione arteriosa polmonare.

Pulmonary Arterial Hypertension (PAH) is an heterogeneous condition brought on by a wide range of causes. It is characterized by structural changes in small pulmonary arteries, that produce a progressive increase in pulmonary artery pressure and pulmonary vascular resistance, ultimately leading to right ventricle failure and death. Given the non-specific nature of its early symptoms and signs, PAH is often diagnosed in its advanced stages. Along with a careful clinical assessment and an accurate electrocardiogram/Chest X-ray interpretation, echocardiography is an essential test in the evaluation of patient with PAH. In fact it not only provides an accurate estimate of pulmonary pressure at rest and during exercise, but may also help to exclude any secondary causes, predict the prognosis, monitor the efficacy of specific therapeutic interventions and detect the preclinical stage of the disease.

Anxiety and depression in COPD patients: The roles of gender and disease severity.

BACKGROUND: The aim of our study was to assess the prevalence of anxiety and depression in the whole chronic obstructive pulmonary disease (COPD) population and in subgroups according to sex and severity classification. A secondary objective was to evaluate the possible differences between patients with and without a significant high level of anxiety, depression, or both, and finally to find out a correlation between psychological aspects, symptoms, functional parameters, and quality of life (QoL). METHODS: Two hundred and two COPD patients were enrolled. Their levels of anxiety, depression, dyspnea, and QoL were assessed using specific questionnaires. One hundred and fourteen sex- and age-matched healthy subjects were used as the control population. RESULTS: The prevalences of anxiety and depression were high (28.2% and 18.8%) in COPD even when it was of mild degree, compared to the control group, in which the prevalence of anxiety and depression were 6.1% and 3.5%, respectively. Female patients had higher levels of anxiety and depression and worse symptom-related QoL. Female patients reported a higher level of dyspnea than males for the same level of ventilatory impairment. Dyspnea was more strongly correlated with depression in women than in men. CONCLUSIONS: Anxiety and depressive symptoms are common in patients affected by COPD, even when their disease is mild in terms of FEV1 and respiratory symptoms. Female patients appear to be more exposed to psychological impairment, which correlates well with some specific symptomatic aspects of the disease, such as dyspnea. Psychological aspects need to be carefully assessed in COPD patients, particularly in females.

Pulmonary arterial hypertension: the key role of echocardiography.

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.

Sputum color as a marker of acute bacterial exacerbations of chronic obstructive pulmonary disease.

We analyzed 795 sputa from 315 patients (233 males, mean age 69.3+/-8.8 years, mean number of exacerbations 2.52/patient) with acute exacerbations of moderate-to-severe chronic obstructive pulmonary disease (COPD) (mean steady-state FEV1 42.5+/-7.8% of predicted). 581/795 sputa were considered adequate. Sputum was analyzed by a quali-quantitative colorimetric scale allowing both color distinction and color degree of intensity. Quantitative culture was then performed (threshold: >10(6)CFU/mL). Samples were distinguished in mucoid (145) and purulent (436) sputa. Absence of bacterial growth was observed in 22% and 5% of mucoid and purulent sputa, respectively. Among mucoid sputa, Gram positive bacterial growth occurred more commonly compared to Gram negative and Pseudomonas aeruginosa/Enterobacteriaceae (56%, 24%, 20%, respectively). In purulent sputa, Gram positives were found in 38% of cases, Gram negatives in 38%, and P. aeruginosa/Enterobacteriaceae in 24%. We evaluated whether functional impairment (FEV1) orientates as to the infectious etiology of exacerbations. Significant differences were observed in the distribution of pathogens. Gram negative and P. aeruginosa/Enterobacteriaceae were isolated more frequently in the sputum when FEV1 was <35%. Our study indicates that purulent sputum is strongly associated with bacterial growth in COPD exacerbations. Deepening sputum color (from yellowish to brownish) was associated with increased yield of Gram negative and P. aeruginosa/Enterobacteriaceae.

Non-phospholipid vesicles for pulmonary glucocorticoid delivery.

In the formulation of inhaled drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD), considerable attention has been devoted to new aerosol morphologies which can either enhance the local effect and/or increase the penetration through the mucus, secreted in bronchial inflammatory diseases. In diseases characterized by bronchial hypersecretion, lipophilic substances, such as corticosteroids, can be remarkably impeded in reaching their receptors, which are localized within the cytoplasm of bronchial epithelial cells. Vesicles consisting of one or more surfactant bilayers enclosing aqueous spaces, are of particular interest because they offer several advantages with regard to chemical stability, lower cost and availability of materials compared to conventional liposomes. With the purpose of carrying out research leading to an innovative formulation for lung delivery capable of permeating the mucous layer, beclomethasone dipropionate, clinically used for the treatment of asthma and COPD, was entrapped in non-phospholipid vesicles. The composition providing the highest entrapment efficiency was chosen. The vesicles obtained after jet nebulization were characterized by means of freeze-fracture microscopy and dynamic light scattering. The efficiency of this new drug delivery system was evaluated in vitro with simulated mucus by means of diffusion experiments (three compartment cell apparatus), using 0.1% mucin gel-like dispersion as a barrier to drug permeation.

Potential role of antibiotics in the treatment of asthma.

Although the role of antibiotic treatment in asthma is still disputed, clinical use of antimicrobials in this setting is more widespread than warranted on the basis of indications in the literature. Viral upper respiratory tract infections are known to be involved in asthma exacerbations. More recently, evidence of Mycoplasma pneumoniae and Chlamydia pneumoniae involvement in asthma attacks has been reported both in adult and paediatric populations. These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease. Recent studies on asthma patients with evidence of atypical infection suggest that specific antimicrobial treatment (basically macrolides or fluoroquinolones) may confer additional advantages compared to standard therapy alone. Furthermore, a considerable amount of data has been gathered describing additional effects associated with macrolide treatment (reduced bronchial hyper-responsiveness, altered cytokine production, etc.). These non-antimicrobial effects have been defined as "anti-inflammatory activity". Should this information be confirmed, the use of macrolides in patients with asthma may be twofold: eradication of occult atypical infection; and reduction in the airway inflammation burden. Future lines of research in this field should attempt to determine whether specific antibiotic treatment may alter the natural history of asthma.

Therapeutic potential of the new quinolones in the treatment of lower respiratory tract infections.

The impact of respiratory infections on public health is increasing and lower respiratory tract infections are a major cause of morbidity and mortality. We are also facing a worldwide burst of antibiotic bacterial resistance. The new fluoroquinolones have an excellent spectrum covering the most important respiratory pathogens, including atypical and 'typical' pathogens. Pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained postantibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of community-acquired pneumonia. This review discusses the more recent data on bacteriological and clinical activity and critically analyses the risks of a potential overuse of this valuable new class of drugs.

Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis.

STUDY OBJECTIVES: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB). DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms. PATIENTS: Outpatients >or= 45 years old with stable chronic bronchitis, smoking history of >or= 20 pack-years, two or more AECBs in the previous year, and FEV(1) < 85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized. INTERVENTIONS: Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]). MEASUREMENTS: Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success. RESULTS: Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03). CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

High levels of interleukin-6 in the exhaled breath condensate of patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. METHODS: We investigated the presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels in exhaled breath condensate may reflect airway inflammation in patients with COPD.

Real-life prospective study on asthma control in Italy: cross-sectional phase results.

OBJECTIVES: To estimate the prevalence of partly controlled and uncontrolled asthmatic patients, to evaluate quality of life and healthcare resource consumption. METHODS: Cross-sectional phase followed by a 12-month prospective phase. Asthma Control Test and the EQ-5D were used. RESULTS: 2853 adult patients recruited in 56 Hospital Respiratory Units in Italy were evaluated: 64.4% had controlled asthma, 15.8% partly controlled asthma and 19.8% were uncontrolled. The mean (SD) EQ-5D score was 0.86 (0.17) in controlled, 0.75 (0.20) in partly controlled and 0.69 (0.23) in uncontrolled patients (p<0.001 between groups). The number of patients requiring hospitalization or emergency room visits was lower in controlled (1.8% and 1.6%, respectively) than in partly controlled (5.1% and 11.5%) and uncontrolled (6.4% and 18.6%). A combination of an inhaled corticosteroid and a long-acting beta-2 agonist was the reported therapy by 56.0% of patients, with the rate of controlled asthma and improved quality of life being higher in patients on extrafine beclomethasone/formoterol compared to budesonide/formoterol (p<0.05) and fluticasone/salmeterol (p<0.05 for quality of life). CONCLUSIONS: Asthma control is achieved in a good proportion of Italian patients. Differences may be detected in a real-life setting in favor of extrafine beclomethasone/formoterol combination.

Seroprevalence of IgG anti-Toxocara species antibodies in a population of patients with suspected allergy.

BACKGROUND: Toxocara canis is an intestinal nematode affecting dogs and cats, which causes human infection when embryonated eggs excreted in dog feces are ingested. Humans are paratenic hosts. Although the larvae do not develop into adult worms in the human body, they may migrate to various tissues and organs where they can survive for several years, giving rise to several clinical symptoms, which can present in allergy-like form. METHODS: Over 5 years, we examined 9985 patients referred for suspected allergies, based on symptoms such as dermatitis, urticaria, rhinitis, asthma, and conjunctivitis; 753 patients who had allergy tests negative or unrelated to clinical history were tested for seropositivity to T. canis by enzyme-linked immunosorbent assay (ELISA) or Western blotting (WB). RESULTS: In 240 patients (31.8%), ELISA or WB or both tests were positive for T. canis immunoglobulin G (IgG) antibodies: in particular, 64 of them (26.7%) were positive to ELISA, 110 (45.8%) to WB, and 66 (27.5%) to both tests. Asthma was the most common clinical presentation. Two thirds of patients underwent subsequent anthelmintic therapy and showed a complete remission of symptoms and, in 43% of patients retested by ELISA and WB, became negative to Toxocara. CONCLUSION: These findings strongly suggest that T. canis plays a significant role in inducing chronic symptoms presenting as suspected allergies.

Evaluating health-related quality of life, work ability, and disability in pulmonary arterial hypertension: an unmet need.

To our knowledge, there are no specific and validated measures of quality of life (QoL) or degree of disability for pulmonary arterial hypertension (PAH). A review of the literature shows that, with the exception of one recently designed specifically for pulmonary hypertension, QoL questionnaires used in PAH studies are generic measures. These are selected because of shared symptoms that do not necessarily correlate well with functional or physiologic measures and have not been validated for applicability in PAH. In this review, we present the available QoL tools for pulmonary artery hypertension and describe the need for more specific instruments that consider the physical and emotional implications of the diseases associated with PAH and the impact of various treatment options. We also discuss the impact of PAH on work ability and the need for provisions to address medical disability status and Social Security benefit status.