Alessandro Zanasi

Antitussive activity of iodo-resiniferatoxin in guinea pigs

Background: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). Methods: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. Results: Pretreatment with I-RTX either intraperitoneally (0.03–0.3 µmol/kg) or by aerosol (0.1–3 µM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 µM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10–100 times more potent than CPZ in all the experimental conditions tested. Conclusions: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation.

Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: a randomized, double-blind, placebo-controlled trial.

Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n = 40) or the homeopathic syrup (n = 40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (p < 0.001 and p = 0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (p < 0.001); however, viscosity was significantly lower in the homeopathic group (p = 0.018). Instead, the subjective evaluation did not significantly differ between the two groups (p = 0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs.

Cough variant asthma and atopic cough

Chronic cough has been reported to be the fifth most common complaint seen by primary care physicians in the world, the third in Italy. Chronic cough in non-smoking, non-treated with ACE-inhibitor adults with normal chest radiogram could be a symptom of asthma and can be sub-classified into: cough-variant asthma, atopic cough, and eosinophilic bronchitis. This review discusses the differential diagnosis of these three disorders.RiassuntoLa tosse cronica è la quinta causa che induce a consultare il proprio medico di famiglia nel mondo, in Italia è la terza. La tosse cronica in un adulto non fumatore che non assume ACEinibitori ed ha una Rx torace nella norma può essere un sintomo indicatore di asma in una delle sue tre varianti: asma variante con tosse, tosse atopica e bronchite eosinofila. La diagnosi differenziale di queste tre patologie è oggetto di questa rassegna.

Virtual Weapons for Real Wars: Text Mining for National Security

Since the end of the Cold War, the threat of large scale wars has been substituted by new threats: terrorism, organized crime, trafficking, smuggling, proliferation of weapons of mass destruction. The new criminals, especially the so called “jihadist” terrorists are using the new technologies, as those enhanced by Web2.0, to fight their war. Text mining is the most advanced knowledge management technology which allow intelligence analysts to automatically analyze the content of information rich online data banks, suspected web sites, blogs, emails, chat lines, instant messages and all other digital media detecting links between people and organizations, trends of social and economic actions, topics of interest also if they are “sunk” among terabytes of information.

Levodropropizine for treating cough in adult and children: a meta-analysis of published studies

BackgroundCough is one of the most common symptoms for which patients seek medical attention from primary care physicians and lung specialists. About 40% of the population at any one time report cough.Cough is associated with significantly impaired health-related quality of life.Levodropropizine is an effective and very well tolerated peripheral antitussive drug. We want to compare it to central cough suppressants efficacy (opioids and non-opioids) that may be associated with side effects limiting their use.MethodsAfter a comprehensive literature search, a meta-analysis of 7 clinical studies of levodropropizine vs. control, including a total of 1,178 patients, was performed with the aim to evaluate the overall comparative efficacy of levodropropizine in the pediatric and adult population.Three electronic databases and reference list were used to search for studies that assessed the efficacy of levodropropizine for treating cough in children and adults using as standardized efficacy parameters the cough frequency and severity, and number of night awakenings as outcome parameters.ResultsThe meta-analysis of all standardized efficacy parameters showed a highly statistically significant difference in the overall antitussive efficacy in favor of levodropropizine vs. control treatments (p = 0.0015).The heterogeneity test for the efficacy outcome was not statistically significant (p = 0.0534).Seven studies met out inclusion criteria. A meta-analysis of the eligible ones showed a statistically significant difference in the overall anti-tussive effect of levodropropizine versus control (p = 0.0015).ConclusionsThis analysis indicates that levodropropizine is an effective antitussive drug in children and adults, with statistically significant better overall efficacy outcomes vs. central antitussive drugs (codeine, cloperastine, dextromethorphan) in terms of reducing cough intensity and frequency, and nocturnal awakenings. This result further reinforces the favorable benefit/risk profile of levodropropizine in the management of cough. The efficacy of levodropropizine in the treatment of cough in children and adults is higher than that of the common centrally-acting anti-tussive.

A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination

Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a β-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a β-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.

Bronchodilator therapy for chronic cough

Experimental studies indicate that airway calibre increases the sensitivity of the afferents involved in the cough reflex but it has proved difficult to demonstrate that airway calibre increases the sensitivity of the afferents involved in the cough reflex. Therefore, bronchodilators might have a role, although rather minor, in the treatment of cough. However, although bronchodilators represent the standard of care in the treatment of airway obstruction associated with asthma or COPD, controversy persists regarding the mechanism(s) by which these agents alleviate cough. Furthermore, the available evidence indicates that the effects of bronchodilators on cough are rather inconsistent in humans and casts doubt on the appropriateness of the common practice of using bronchodilators in the treatment of patients with cough without any other evidence of airway obstruction. Regrettably, appropriate long-term trials specifically aimed at evaluating the clinical efficacy of bronchodilators in pathologic cough have not yet been performed. Therefore, properly executed clinical studies of bronchodilators in various types of acute and chronic pathologic cough are required.

A reappraisal of the mucoactive activity and clinical efficacy of bromhexine

Since its introduction to the market in 1963, bromhexine, an over-the-counter drug, has been investigated for its activity in animal models and in humans with diverse respiratory conditions. Bromhexine is a derivate of the Adhatoda vasica plant used in some countries for the treatment of various respiratory diseases. Bromhexine has been found to enhance the secretion of various mucus components by modifying the physicochemical characteristics of mucus. These changes, in turn, increase mucociliary clearance and reduce cough. Principal clinical research studies were primarily developed in an era when stringent methodological approaches and good clinical practices were not developed yet. Clinical studies were conducted mainly in patients with chronic bronchitis and in patients with various respiratory diseases, and demonstrated the efficacy of bromhexine in improving respiratory symptoms. Furthermore, the co-administration of antibiotics with bromhexine amplified the actions of the antibiotic. Although the clinical evidence shows only modest but positive results, bromhexine is indicated for its mucoactive activity. Larger trials with adequate methodology are required to identify when treatment with bromhexine can improve clinical outcomes.

Survey on attitudes of Italian pediatricians toward cough

Context Children’s cough is a daily concern for most pediatricians. The management of both acute and chronic cough requires a systematic and comprehensive approach. Despite the approved protocols for management, the pediatric assessment of cough and the corresponding prescribing attitude frequently do not fit these protocols, which can be affected by parental suggestions – sometimes substantially. Objective The objective of this study was to investigate both the perception and the behavior of a representative sample of Italian pediatricians toward cough in real life. Methods A specific questionnaire consisting of 18 questions was prepared. The questionnaire was completed by 300 pediatricians (all members of PAIDOSS: Italian National Observatory on Health of Childhood and Adolescence) who represented ~300,000 children. Results A vast majority of children have cough throughout the year (99.3% of respondents have cough during autumn/winter and 64.7% in spring/summer). Allergic disease is the most frequent suspected cause of chronic cough in children (53%), and this is supported by the high demand for consultations: 73% seek the opinion of allergologists, 62% of otorhinolaryngologists and only 33% of pulmonologists. The majority of pediatricians (92%) reported that they prescribe therapy in acute cough regardless of cough guidelines. Moreover, the survey pointed out the abuse of aerosol therapy (26% in acute cough and 38% in chronic cough) and of antibiotics prescription (22% in acute cough and 42% in chronic cough). Conclusion Our survey suggests that some Italian pediatricians’ therapeutic attitudes should be substantially improved in order to achieve better management of cough in children and to minimize the burden of cough.

Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients.