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Objective Bleomycin is one of the most commonly used agents in sclerotherapy for slow-flow vascular malformations worldwide. However, its efficiency remains unknown. The objective of the present study was to assess whether reversible electroporation combined with bleomycin would increase the sclerotherapy effect in patients with previously unsuccessfully treated venous malformations (VMs). Methods We performed, to the best of our knowledge, the first retrospective observational case series from January 2019 to January 2020 of 17 patients (20 lesions) with symptomatic VMs, who had previously undergone at least two unsuccessful invasive treatments. Reversible electroporation was performed with various electrodes and directly injected bleomycin. All patient records, magnetic resonance imaging data, documentation of previous treatments, and data regarding the intervention, complications, and clinical symptoms were analyzed. Results The 17 VM patients (mean age, 20.8 ± 8.2 years; 9 females) had previously undergone an average of 4.2 invasive treatments. These patients had subsequently undergone 22 electrosclerotherapy sessions of 20 lesions. The median dose of bleomycin was 3 mg. The median magnetic resonance imaging-derived lesion volume before treatment was 24.9 cm3, which had decreased by 86% to 3.5 cm3 after treatment. After 3.7 months, eight patients were asymptomatic without residual symptoms and nine patients showed improvement. Conclusions Bleomycin electrosclerotherapy appears to be an effective therapy for patients with VMs resistive to previous invasive therapy. Because of the small sample size and short follow-up period, our results should be examined further using a larger patient population.

Cough is a protective reflex that serves to clear the airways of excessive secretions and foreign matter and which sometimes becomes excessive, and troublesome to patients. Cough is one of the most common reasons why individuals seek medical attention. A range of drugs have been developed in the past with antitussive activity and different mechanisms of action, but there are still very few safe and effective treatments available. The poor tolerability of most available antitussives is closely related to their action on the central nervous system (CNS). An international group of experts specialized in cough met to discuss the need to identify an effective antitussive treatment with a good tolerability profile. The aim of this expert review is to increase the knowledge about the cough mechanism and the activity of levodropropizine, a peripherally acting antitussive drug.

Chronic respiratory diseases (CRD) belong to major noncommunicable diseases (NCD) targeted by World Health Organization (WHO) NCD Action Plan and United Nations (UN) Sustainable Development Goal (STG) 3.4 to achieve 30% decline of mortality by the year 2030. Strong evidence is now available in the literature for therapeutic aquatic exercise interventions in improving health status of chronic obstructive pulmonary diseases (COPD) patients. However, gym-based exercises can be difficult for patients with COPD who are mainly elderly and often have co-morbidities-such as severe arthritis and obesity-which may impair their ability to exercise at an adequate intensity. Besides improving respiratory function and health status in COPD, exercise in water helps overcoming patient's fears and promote socialization, contrasting the risk of depression, which is a major condition often associated with long term COPD condition. Susceptibility to respiratory infections plays a role in exacerbations of COPD. Sulphur-rich water inhalations improve muco-ciliary clearance, reduce inflammatory cytokines production and inflammatory mucosal infiltration, reduce elastase secretion by neutrophils, preserving elastic properties of pulmonary interstitium and thus facilitating expectoration. Repeated cold water stimulations in COPD also reduce frequency of infections. Finally, sauna bathing reduces the risk of pneumonia. On the other side, hydrotherapy/balneotherapy also help obesity control, which is one of the most difficult NCD risk factors to modify and consequently is an important component of the WHO preventive strategy to achieve STG 3.4. Along with high prevalence and mortality, CRD cause increasing pharmaceutical and hospital costs. In this perspective, Health Resort Medicine should not be ignored as a resource in the WHO NCD strategy and Universal Health Coverage, providing a multi-stakeholder platform (including the network of health resorts and their facilities) able to give a real help to the achievement of UN goal STG 3.4 by the year 2030.

Background: Influenza and influenza-like syndromes (I-LSs) are infectious diseases occurring on a seasonal basis which can lead to upper (URTI) and lower respiratory tract illness (LRTI) of different severity. The approach to these disorders is unfortunately not uniform. Aim of the study was to investigate real-life people beliefs, the attitude to their prevention and treatment, and their impact in general population. Methods: A cross-sectional survey via Computer Assisted Telephone Interview (CATI) was carried out using a specific questionnaire investigating influenza episode rates, subjects behavior in case of influenza and I-LSs, and prescribed therapy. Results: 1,202 subjects completed the questionnaire: median age was 46, 49% male, 20% active smokers. 57% of respondents experienced at least one episode of influenza or I-LS in the previous 12 months; episodes were usually homemanaged, shorter than 2 weeks and more frequent in fall and winter (73% of the total). GP resulted the first health-care option (56%); almost 3% of respondents referred to the emergency room, and hospitalization occurred in 1%. Mucolytics resulted the most prescribed drugs (55%) followed by antibiotics and aerosol therapy (37–38%). Even if more than 70% of subjects considered vaccination essential, only 14% received influenza vaccination yearly and almost 60% had never received vaccination. Approximately 36% of respondents regarded homeopathy (namely Oscillococcinum) as an helpful alternative because of perceived as safer. Conclusions: Seasonal prevalence of I-LSs and influenza partially overlap. As virus identification is not a common procedure in daily practice, only a clinical discrimination is possible. Antibiotic prescription is still too high and largely inappropriate. Influenza vaccination is strongly encouraged, but different strategies are also used. Other approaches are receiving increasing attention in general population, and subjects’ willingness to spend out-of-pocket for effective remedies is also increasing. The discrepancy between subjects’ beliefs and health care actions likely reflects the insufficiency of institutional preventive strategies. In general, the approach to influenza and I-LSs appear variable and highly dependent of subjects’ and their GPs’ cultural beliefs.

Background Acute cough is the most common symptom among children in primary care, but the impact of cough episodes was never investigated in Italian families. Methods A cross-sectional telephone survey was conducted on a representative sample of Italian families, randomly selected from general population; a specific and validated questionnaire was used. Results The sample (604 calls) was uniform by geographical distribution, and by children age and gender. Mean cough episode was 3.1/year, they were short lasting (only 4.7% > 2 weeks). Independent predictors of children cough episodes were parents’ active smoking habit and work (p € 30 in 18.4% of cases). Conclusions Parents’ actions against cough episodes were variable, depending on their beliefs, smoking habit, and occupational status. The parents’ perceived efficacy of usual prescriptions is poor, and their willingness to pay out-of-pocket for an “effective remedy” against cough is high. The interest for alternative treatments is not negligible in these circumstances. Electronic supplementary material The online version of this article (10.1186/s40248-019-0180-9) contains supplementary material, which is available to authorized users.

This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms. Hereby we report the abstracts of the works submitted for publication in this Meeting report. The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough. Electronic supplementary material The online version of this article (10.1186/s40248-018-0130-y) contains supplementary material, which is available to authorized users.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Eur Respir J. 46 (2015) PA3852, http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

The development of mobile devices as well as social media platforms recently lead to the necessity of monitoring the latter during crisis and emergency situations. Paradoxically, the huge amount of information available through these new sources may lead to information gaps, within the Public Safety Organization operators' awareness. We describe some specific types of information gaps due first to imprecise or unreliable information and second to information overload. We then propose a set of tools aiming at reducing these information gaps and supporting the human operators in the social media generated information during crisis and emergency management. The first tool aims at geolocalising tweets relying on the content of the messages. The second tool provides sentiment analysis and clustering of multi-lingual messages and the third tool provides means for semantic information fusion and hypothesis evaluation relying on the contents and metadata of the tweets reporting about an event.

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.

Alessandro Zanasi,1 Luigi Morcaldi,2 Salvatore Cazzato,3 Massimiliano Mazzolini,4 Marzia Lecchi,5 Antonio Maria Morselli-Labate,6 Marianna Mastroroberto,6 Roberto W Dal Negro7 1Italian Association for Cough Study, Bologna, 2National Observatory of Health in Childhood and Adolescence (PAIDOSS: Osservatorio Nazionale sulla Salute dell’Infanzia e dell’Adolescenza), Rome, 3Department of Pediatrics, Salesi Children’s Hospital, Ancona, 4Department of Specialist, Diagnostic and Experimental Medicine, Respiratory and Critical Care Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, 5Department of Biotechnology and Biosciences, University of Milan Bicocca, Milan, 6Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, 7National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy 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. Keywords: acute cough, chronic cough, cough in children, pediatricians’ prescriptions, cough impact

Objective: During the last decades, an increase in the prevalence of asthma and other allergic diseases has been recorded, together with modifications in the living environment and consequent changes in the quality of indoor air. Indoor environment is favorable to the proliferation of allergens such as: house dust mites, fungal spores and cockroaches. The primary action to be undertaken for an effective eradication of infectious agents constitutes in modifying the house environmental conditions, which make it favorable to infestations. Ozone can play a sanitize role, but at the same time it can cause inflammation, especially in the lung. The aim of this study was to verify the role and safety of ozone in the sanitation of the bedroom of a subject suffering from asthma. Methods: A daily ozone treatment was carried during a 14-day time period in the bedroom of an asthmatic patient. Aerobiological sampling in indoor air, microbiological sampling and detection of ATP bioluminescence on the surface were performed before and after treatment at the first day, as well as after treatment at the 7th and 14th day of the study. An aerobiological measurement was also performed outdoor of the patient's bedroom only for the first day. Results: Our analysis confirms that low ozone levels induced a marked reduction of indoor air microbiological pollution without adverse effects on lung functionality of the asthmatic patient we considered. Conclusion: Our observations warrant further investigation on the role that ozone-based sterilization might have in controlling asthmatic symptoms.

Background Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO2 rebreathing test in patients with chronic cough of any origin. Methods Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO2 for 5 min. Fractional end-tidal CO2 (Fetco2) and inspiratory minute ventilation ( V ˙ i) were continuously monitored. Changes in breathing pattern variables were also assessed. Results At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P Conclusions The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. Trial Registry European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/

Background Cough is one of the most common discomforts affecting general population, which can disrupt subjects’ quality of life due to its physical, social, and psychological effects. Aim of the study was to investigate the impact of cough and related beliefs of general population. Methods A cross-sectional telephone survey was carried out by means of a specific, validated questionnaire on a representative sample of Italian general population. All the interviews were carried out according to the Computer Assisted Telephone Interview (CATI) methodology by expert, professional interviewers. Distributions of all answers were calculated in the overall sample. Results A total of 1,251 subjects (mean age: 49 years; females 44.2 %) completed the interviews. The overall number of telephone calls was 5362, and the corresponding redemption rate was 1/4.3 (23.%). The sample was representative of national population in terms of geographical distribution, age, gender, and smoking habit. The majority of respondents was convinced that cough is merely a symptom of several different diseases, but 46.4 % of respondents affirmed that cough should be regarded as “a disease” per se. Only 29.1 % of subjects say that they usually do not complain of any cough over the year, while 18.4 % reported ≥ 3 episodes of cough/year. These episodes have a duration ranging 10–30 days in 19.9 % of subjects, and > 30 days in 6.9 % of subjects. The majority of respondents is worried about their cough only after 1 week, but 76.9 % of subjects is much more worried if cough affects a child. After a few days of cough, 23.1 % of subjects use domestic remedies; 20.9 % ask their pharmacist, and 33.4 % their doctor, being GPs (69.6 %) and lung physicians (16.2 %) the most asked professionals. The occurrence of bronchitis, pneumonia, upper airway infections, and allergic troubles are the most feared events. The majority of respondents are convinced that antibiotics and steroids should not be regarded as the gold standard for treating persistent cough (61.2 and 58.2 %, respectively), while anti-tussive drugs and aerosols in general are regarded as the most effective strategies (69.1 and 74.1 %, respectively). Moreover, 33.8 % of the sample is in favour of homeopathic drugs, while 23.2 % had already used an homeopathic anti-tussive syrup, and 27.6 % of subjects are really interested in using the homeopathic approach. The willingness to pay for an effective anti-tussive remedy was: 46.3 % up to 10 €; 27.8 % up to 20 €, and 13.3 % more than 20 €. Conclusions Cough confirms its high impact in Italy, and a substantial proportion of individuals regards cough as “a disease”. Only one out of three Italians refers to their doctor, but when cough is already persistent. Cough in children is much more feared than in adults. The majority of Italians have a proper and conservative position versus both antibiotic and the systemic steroid uses against cough. The Italian attitude to aerosol therapy confirms very high. Differently from the cough guidelines, anti-tussive drugs are highly valued among Italian people. The attitude and the interest to homeopathic anti-tussive remedies proves high. Finally, the willingness to pay for an effective anti-tussive remedy is quite high in Italy. Electronic supplementary material The online version of this article (doi:10.1186/s40248-016-0072-1) contains supplementary material, which is available to authorized users.

Background: Acute cough is one of the most frequent symptoms prompting a visit to a health care provider, usually following a viral upper respiratory tract infection (URTI). The disproportionate use of antibiotics in children with URTIs, recently highlighted in the medical literature, could lead to associated side effects, without any beneficial effect. Although an early, albeit inappropriate, antibiotic prescription increases parental satisfaction, URTIs are predominantly viral infections and are generally self-limiting. Therefore the aim of this study was to analyze the effectiveness of antibiotics compared to symptomatic drugs (central and peripheral antitussives) on URTI-related cough in a pediatric population. Methods: This is a prospective observational study of 330 children who required pediatric consultation for acute cough. Severity, frequency and type of cough were assessed at baseline and after 6 days of treatment (antitussives n = 123, antibiotics n = 89 or combination of them n = 38) or no treatment (n = 80). The outcome of cough management after 6 days was analyzed in terms of resolution, improvement, no change or worsening of symptoms. Study assessments were performed using a standardized questionnaire administered to parents. Results: Between children treated with antitussives or antibiotics, there was a statistically significant difference in the resolution of cough. Moreover, if considering peripheral antitussives, the resolution of cough was significantly higher with antitussives than with antibiotics (p < 0.01). There was no difference in cough resolution between children treated with antitussives and those receiving a combination of antibiotics and antitussives, either central and peripheral antitussives. Conclusion: Antibiotics are generally not useful nor appropriate in treating acute cough due to the common cold. Furthermore, inappropriate antibiotic use introduces the possibility of adverse side effects as well as promotion of antibiotic resistance. The findings of the present study suggest that antitussives, especially peripherally acting agents, represent an effective treatment option for acute pediatric cough caused by URTIs.

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.

Cough is the one of the most common respiratory symptoms for which medical attention is required and may have a great impact on quality of adults9 life, thus often requiring an empiric treatment with antitussive agents .There are evidence that NSAIDs are also used to improve cough concerning common cold. We have performed a prospective study evaluating 149 patients affected by URTI treated with some combination of NSAIDs and antitussives. Cough was measured by means of a verbal category descriptive (VCD) score. We have considered two periods, 7 and 10 days respectively, from the start of the treatment. On VCD score was conducted an analysis of persistence of cough (Kaplan Meier) taking into account absence of coughing (score=0) or its presence (score>0). The drugs more frequently used was levodropropizine and ketoprofen lysine salt. There was a statistically significant difference in time resolution of cough between the group receiving ketoprofen lysine salt and levodropropizine (a peripheral antitussive) and the group treated with ketoprofen lysine salt and central acting antitussives, in favor of the first combination. In patients treated with ketoprofen lysine salt and a central acting antitussives the median persistence of cough was 11 days, while in the group treated with ketoprofen lysine salt and levodropropizine the median was of 7 days. The present study suggests that the association of antitussives with NSAIDs, such as levodropropizine with NSAIDs, is efficacious in the reduction of coughing days and that the combination levodropropizine and ketoprofen lysine salt shows better result compared with levodropropizine and central antitussive.

Background. The effectiveness of a homeopathic syrup on cough has been demonstrated in an adult population in a previous double-blind randomized study. The present prospective observational study investigated children affected by wet acute cough caused by non-complicated URTIs, comparing those who received the homeopathic syrup versus those treated with the homeopathic syrup plus antibiotic. Objectives. The aims were: 1) to assess whether the addition of antibiotics to a symptomatic treatment had a role in reducing the severity and duration of acute cough in a pediatric population, as well as in improving cough resolution; 2) to verify the safety of the two treatments. Methods. Eighty-five children were enrolled in an open study: 46 children received homeopathic syrup alone for 10 days and 39 children received homeopathic syrup for 10 days plus oral antibiotic treatment (amoxicillin/clavulanate, clarithromycin, and erythromycin) for 7 days. To assess cough severity we used a subjective verbal category-descriptive (VCD) scale. Results. Cough VCD score was significantly (P

Background: Cough 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. Methods: After 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. Results: The 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). Conclusions: This 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.

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.

BACKGROUND: A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor. METHODS: This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath. RESULTS: The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P = 0.014). DISCUSSION: The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers. CONCLUSIONS: The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02102191.

Congenital central hypoventilation syndrome (CCHS) is defined as failure of the chemical (autonomic) control of breathing causing alveolar hypoventilation in the absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions. Hypoventilation is predominant in non-rapid-eye-movement sleep, during which breathing is primarily under chemical control. Failure of the central integration of chemosensory inputs is proposed as the putative defect. A genetic basis for CCHS is supported by lines of evidence. In some diseases of the central nervous system there is more or less complete depression of the cough reflex, whereas spontaneous ventilation is generally preserved. Little is known regarding cough in CCHS patients. Parents consistently report that their children cough ‘normally’ during airway infections; in contrast, experimental lines of evidence suggest that CCHS children lack a cough response following inhalation of a tussigenic agent. Although several factors may account for the discrepancy, the possibility of a weakened or even absent cough reflex remains to be fully ascertained. Conceivably, a defective cough reflex, in conjunction with the well established lack of perception of respiratory discomfort, might result in an increased risk of potentially serious respiratory complications in CCHS patients.

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.

Background: Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications. This has led to the current interest in developing effective oral or intranasal preparations. Objective: This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults. It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant. Methods: This was a multicenter, Phase I, randomized, open-label pilot study in which the primary end point was immunogenicity (hemagglutination-inhibition [HI] antibody assay on days 1 and 29). The secondary end point was the frequency of adverse events (AEs). Subjects were assigned to 4 vaccination groups: groups AI, AII, and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used, and group B received intramuscular virosomal subunit vaccine. Assessments of health status, hematology, biochemistry, body temperature, heart rate, blood pressure, and incidence of AEs were made on days 1, 8, and 29, and serology was assessed on days 1 and 29. Results: The study enrolled 88 subjects. All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered (A/Singapore, A/Texas, A/Wuhan, B/Beijing), with no notable immunogenic differences between lots. After intranasal vaccination, geometric mean titers (GMT) increased 2.7-fold against A/Singapore (group AI); 1.8- and 3.1-fold against A/Texas (groups AII and AIII, respectively); 1.9- to 2.4-fold against A/Wuhan; and 1.5- to 1.7-fold against B/Beijing. After intramuscular vaccination, GMT increased 11.3-, 6.3-, and 2.7-fold against A/Texas, A/Wuhan, and B/Beijing, respectively. Seroprotection (HI antibody titers ≥1:40 in >70% of those vaccinated) was achieved against all strains in the group that received intramuscular vaccination, against A/Wuhan in all groups that received intranasal vaccination, and against A/Texas in group AII. Both vaccine formulations were well tolerated. Intranasal vaccination was associated with a low incidence ( Conclusions: Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated. The different batches of intranasal vaccine showed a similar immunogenic profile. Intranasal administration may be preferred to intramuscular administration by some patients.

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 is a frequent symptom reported in general practice consults. Even though most of the cases concern acute and self limiting episodes, if cough persists a comprehensive diagnostic evaluation should be started. Patients that scarcely respond to empiric therapy or whose symptoms are not clearly referable to one of the most common causes of cough may receive the diagnosis of unexplained cough. These patients frequently develop depression or social retirement. Recent studies have suggested that hypersensitivity of the cough reflex could be the pathogenic mechanism underlying unexplained cough. However hypersensitivity syndrome should not be used as an easy way out for patients with a complicated history of cough. Through our paper we will briefly review the most common causes of cough and how they could be involved in the development of hypersensitivity cough syndrome.

A new paradigm has appeared in computer science in the recent years: data mining. The success of this new approach comes from recent advances in three different, yet connected fields: mathematics—new efficient and quick algorithms have been developed; database technologies—new research has allowed the improvement of databases; computer power—new powerful computers and architectures have made possible the elaboration of huge data volumes. Data mining's applications to the business world are several and include database marketing, basket analysis, and crime detection. In this article, the author discusses the application of data mining to competitive intelligence analysis. © 1998 John Wiley & Sons, Inc.

Several tools are already available in the text mining (or more generally unstructured data) quickly growing market. We recognize the text mining market as composed by pure players (companies which develop text mining software, e.g. Clearforest, Inxight, Temis), indirect players (which integrate text mining into their offering, e.g. IBM, SAS, SPSS), partial players (companies which use text mining to improve their core business, e.g. Fast, Verity). A section is dedicated to each player which provided us with their company description, and a cumulative section listing the most known players in the text mining arena. Hundreds of other companies are already working successfully in the worldwide market. For a list of them, go to www.kdnuggets.com.

In a world where all the organizations, thanks to Internet, are “global” organizations, only those ones with a knowledge advantage may provide a competitive service and survive. This advantage is based on the capability of recognizing the global market needs coming from an environment consisting in technology, organizations (companies, governments, associations), people (customers, citizens, employees) and their opinions, actions and production. Only who will know how to retrieve, analyze and turn into actionable intelligence documents, web pages, emails, chat lines and, generally, public/open sources content, will be able to acquire and maintain this knowledge advantage. A new area, online analysis by text mining, is available to perform this task. An introduction to Temis and to its text mining technology, with some indications about Temis current research directions are here given.

Francesco De Blasio1, Luigi Lanata2, Peter V. Dicpingaitis3, Federico Saibene2, Rossella Balsamo2, Alessandro Zanasi4 1Respiratory Medicine and Pulmonary Rehabilitation Section, Clinic Center, Private Hospital, Naples, Italy 2Medical Department, Dompe SPA, Milan, Italy 3Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA 4Pneumology Unit, University of Bologna, S.Orsola Malpighi Hospital, Bologna, Italy

Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action.

Chronic cough has been reported to be the fifth most com- mon 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 bron- chitis. This review discusses the differential diagnosis of these three disorders.