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We study the enhancement of third harmonic generation in indium tin oxide nanolayers coupled to Tamm plasmon polaritons (TPPs). The TPPs are excited at the interface between a thin gold mirror and a silicon dioxide/silicon nitride (SiO2/Si3N4) distributed Bragg reflector with a 30 nm thick indium tin oxide (ITO) nanolayer embedded inside the topmost dielectric layer under the metal mirror. This ITO nanolayer exhibits epsilon-near-zero (ENZ) behavior at near-infrared wavelengths. By tuning the angle of incidence and the TPP resonance conditions, we achieve sub-wavelength confinement of the electromagnetic field, resulting in an 8× enhancement of the nonlinear optical response of the structure compared with the isolated ITO nanolayer at its optimal ENZ condition. We further investigate the dependence of the THG signal on the incident angle and sample orientation, confirming that the enhancement is driven by the excitation of the TPP mode with a characteristic asymmetric behavior. Numerical simulations of local field factors based on the transfer matrix method fully support our findings. Our study demonstrates that the TPP-ENZ platform offers a versatile and highly efficient approach to enhancing nonlinear optical processes, with potential applications in frequency conversion, optical signal processing, and the development of more efficient nonlinear photonic devices.

Roberto W Dal Negro,1 Paola Turco,1 Massimiliano Povero2 1National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology - CESFAR, Verona, Italy; 2AdRes Health Economics and Outcomes Research, Turin, ItalyCorrespondence: Massimiliano Povero, Email m.povero@adreshe.comBackground: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost.Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO).Methods: COPD patients aged ≥ 40 years of both genders were recruited consecutively and labelled by computed tomography as “with significant” emphysema (> 10% of CT lung volume) or “with negligible” emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC).Results: Thirty-one patients with “significant emphysema” were compared to thirty-one with “negligible emphysema”. FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema.Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.Keywords: COPD, parenchymal destruction, emphysema, lung capillary blood volume, simultaneous single-breath NO and CO diffusing capacity, precision medicine

Background: Patients’ compliance to inhalation therapy is usually sub-optimal in young asthmatics. Adolescents poorly compliant to regular anti-asthma treatments and those with tattoos (and the associated attitude) can share some personality traits and maladaptive behaviors. This relationship has not been investigated. Objective: To assess if “extended” tattoos can predict long-term compliance to regular therapy of adolescents with mild-to-moderate asthma. Methods: A 12-month retrospective observational investigation was conducted on non-smoker asthmatic adolescents of both genders. Patients assuming 2, respectively. The relationship between tattoos and compliance on the evolution of resources consumption at 6 and 12 months was assessed by generalized estimating equation (GEE) models at the first and second semester of the treatment period. Results: It was found that 13.2% of compliant adolescents had mild tattoos, while 47.2% of non-compliant adolescents had mild-to-extended tattoos (odds ratio (OR) 6.91, 95% CI 2.49 to 19.17, p < 0.001). The mean annual adherence to treatment was 57.8% ± 10.1 SD expected doses in non-compliant subjects with “mild tattoos” (54.8 cm2 ± 36.9 SD), but 38.6% ± 11.4 SD expected doses in those with “extended tattoos” (568.4 cm2 ± 111.6 SD, p < 0.001). Total cost proved to be a linear trend from the lowest values of compliant patients with no/mild tattoos (EUR 65.22 at 6 months and EUR 33.63 at 12 months) to the highest values of non-compliant adolescents with extended tattoos (EUR 330.75 at 6 months and EUR 297.34 at 12 months). Conclusions: Tattoo extension might be used as a reliable predictor of poor compliance and higher health care costs in adolescents with mild-to-moderate asthma. Patients characterized by poor compliance to a long-term therapeutic strategy and tattooing attitude likely share some aspects of their personality profile.

In this paper, we introduce a fully non-perturbative approach for the description of the optical nonlinearity of epsilon-near-zero (ENZ) media. In particular, based on the rigorous Feynman path integral method, we develop a dressed Lagrangian field theory for light–matter interactions and discuss its application to dispersive Kerr-like media with order-of-unity light-induced refractive index variations. Specifically, considering the relevant case of Indium Tin Oxide (ITO) nonlinearities, we address the novel regime of non-perturbative refractive index variations in ENZ media and establish that it follows naturally from a scalar field theory with a Born–Infeld Lagrangian. Moreover, we developed a predictive model that includes the intrinsic saturation effects originating from the light-induced modification of the Drude terms in the linear dispersion of ITO materials. Our results extend the Huttner–Barnett–Bechler electrodynamics model to the case of non-perturbative optical Kerr-like media providing an intrinsically nonlinear, field-theoretic framework for understanding the exceptional nonlinearity of ITO materials beyond traditional perturbation theory.

Northeastern Italy offers several sites where a variety of German is in contact with Italian, Italo-Romance, or Rhaeto-Romance: All of these contact situations vary according to sociolinguistic and extralinguistic factors, such as the composition of the speech community, structure of linguistic repertoires, language status, standardization, and demography. These factors combine into more or less coherent speech community types that, in turn, constrain the typology of contact linguistic phenomena that can be observed. In this contribution, based on the trilingual region of South Tyrol, a few emblematic case studies will be discussed focusing on insertional mechanisms that occur in speech. Based on the outcomes of a larger research project and drawing on various corpora of conversational data, quantitative and qualitative aspects of this contact situation will be explored in more detail.

Peter MA Calverley,1 Alberto Papi,2 Clive Page,3 Paola Rogliani,4 Roberto W Dal Negro,5 Mario Cazzola,4 Arrigo F Cicero,6 Jadwiga A Wedzicha7 1Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK; 2Respiratory Medicine, University of Ferrara, Ferrara, Italy; 3Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King’s College, London, UK; 4Respiratory Medicine Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 5National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 6Medical and Surgical Department, University of Bologna, Bologna, Italy; 7Respiratory Division, National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: Peter MA Calverley, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK, Tel +44 1515295886, Fax +44 1515295888, Email pmacal@liverpool.ac.ukPurpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity.Patients and methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patient-reported HRQoL (St George’s Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student’s t-tests or ANCOVA as appropriate.Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures.Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity.Keywords: antibiotic, chronic obstructive pulmonary disease, erdosteine, COPD exacerbation, health-related quality of life, systemic corticosteroid

We study the enhancement of third harmonic generation in indium tin oxide nanolayers coupled to Tamm plasmon polaritons (TPPs). The TPPs are excited at the interface between a thin gold mirror and a silicon dioxide/silicon nitride (SiO2/Si3N4) distributed Bragg reflector with a 30 nm thick indium tin oxide (ITO) nanolayer embedded inside the topmost dielectric layer under the metal mirror. This ITO nanolayer exhibits epsilon-near-zero (ENZ) behavior at near-infrared wavelengths. By tuning the angle of incidence and the TPP resonance conditions, we achieve sub-wavelength confinement of the electromagnetic field, resulting in an 8× enhancement of the nonlinear optical response of the structure compared with the isolated ITO nanolayer at its optimal ENZ condition. We further investigate the dependence of the THG signal on the incident angle and sample orientation, confirming that the enhancement is driven by the excitation of the TPP mode with a characteristic asymmetric behavior. Numerical simulations of local field factors based on the transfer matrix method fully support our findings. Our study demonstrates that the TPP-ENZ platform offers a versatile and highly efficient approach to enhancing nonlinear optical processes, with potential applications in frequency conversion, optical signal processing, and the development of more efficient nonlinear photonic devices. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a chronic disease related to the atopic condition in most cases but also to other factors (such as infectious diseases; social, economic, environmental, and occupational conditions; exposure to biological irritants; and/or chemical aggressions) [...]

Bronchial asthma is characterized by variable airflow obstruction, airway inflammation, and bronchial hyperresponsiveness (BHR) to non-specific stimuli. The role of underlying airway inflammation and of related long-lasting BHR has been suboptimally investigated in teenagers with mild-to-moderate asthma, as has the corresponding economic impact over time. The aim of the present study was to calculate the cost of mild-to-moderate atopic asthma in teenagers arising from their degree of persisting BHR over a twelve-month period. Methods: Patients aged 12–18 years with mild-to-moderate symptoms treated with fluticasone fumarate/vilanterol 92/22 mcg daily were retrospectively followed for 12 months. Usual spirometric parameters, BHR to methacholine (MCh), and resource consumption (visits, hospitalizations, systemic steroids and/or antibiotics courses, school days off) were assessed at recruitment (the index date) and after 6 and 12 months. Adherence to treatment was also calculated. The cost of asthma was calculated based on Italian tariffs and published papers. The trend over time in BHR and the association between response to MCh and total cost were investigated by using regression models adjusted for repeated measures. Results: 106 teenagers (53 males, age 15.9 ± 1.6 years) were investigated. The annual cost of asthma proved significantly related to the BHR trend: every increment of a factor 10 in the response to MCh was associated with a saving of EUR 184.90 (95% CI −305.89 to −63.90). BHR was progressively optimized after 6 and 12 months in relation to the patients’ compliance to treatment (≥70% of prescribed inhalation doses). Conclusions: the usual spirometric parameters are largely insufficient to reflect the effects of underlying persistent inflammation in milder forms of asthma in teenagers. In terms of clinical governance, the periodic assessment of non-specific BHR is the appropriate procedure from this point of view. Non-specific BHR proves a reliable procedure for predicting and monitoring the economic impact of mild-to-moderate asthma in teenagers over time.

L’apprendimento delle lingue al museo presenta una serie di opportunità nella didattica delle lingue straniere. I musei offrono infatti una varietà pressoché inesauribile di temi e materiali stimolanti e culturali che costituiscono una piacevole alternativa, da una parte a certi contenuti ripetitivi e superficiali di alcuni corsi di lingua, dall’altra a tutti quegli approcci fin troppo funzionali che vedono la lingua esclusivamente in vista di qualcosa di “utile”, vuoi che sia il lavoro, lo studio o un viaggio. In questo mio contributo mi propongo di descrivere diversi settings di didattica al museo (l’apprendimento in tandem, un corso di lingua, un’offerta in autonomia per i centri di autoapprendimento, il formato online), basandomi in parte sugli studi nell’ambito della didattica “fuori dall’aula”, ma soprattutto sulle mie esperienze personali di insegnante, ed anche di apprendente di lingue straniere. Completerò questo mio resoconto enumerando alcuni tratti comuni delle forme di apprendimento linguistico fuori dall’aula, in particolare di quelle praticate in contesto museale.

Roberto W Dal Negro,1 Paola Turco,2 Massimiliano Povero3 1National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 2Research & Clinical Governance, Verona, Italy; 3AdRes Health Economics and Outcome Research, Torino, ItalyCorrespondence: Massimiliano PoveroAdRes Health Economics and Outcome Research, Torino, ItalyEmail m.povero@adreshe.comBackground: The MiniBox+™ is an innovative technique for assessing lung volumes (LVs) and the diffusing capacity of the lung for carbon monoxide (DLco). Differently from the equipment needed for whole body plethysmography (WBP), the MiniBox+ is a small, transportable instrument, which derives total lung capacity (TLC) during tidal breathing by analyzing gas pressures and airflows immediately preceding and immediately following airway occlusions.Aim: To compare the consistency and the feasibility of LV and DLco measurements between the two instruments in different lung function disorders, and their cost of execution.Methods: Consecutive patients of both genders with obstructive and restrictive respiratory disorders were randomly recruited. LVs and DLco were measured by a randomized sequence. The failure risk, number of attempts to achieve the first reliable measurement, corresponding time spent, and costs per patient were compared.Results: A total of 134 patients were enrolled: 42 asthmatics (32.1%), and 47 patients with obstructive (35.1%) and 44 with restrictive respiratory disorders (32.8%). The overall failure risk was 19.4% for WBP and 8.2% for the MiniBox+ (risk ratio=0.417, 95% CI 0.242 to 0.72). LVs and DLco values proved equal with both techniques, regardless of the patients’ age, sex, schooling level, and initial lung disorder. Number of attempts and total time spent in achieving the first reliable measurement were significantly lower with the MiniBox+. Mean cost per patient was € 87.58 with WBP and € 75.11 with the MiniBox+, with a mean saving of € 12.33 (95% CI 5.93 to 18.73), mainly due to the saving in productivity loss.Conclusion: LV and DLco measurements with the MiniBox+ were highly consistent with those obtained with WBP. The MiniBox+ proved easier to use (lower failure risk) and more convenient (lower execution costs) than WBP.Keywords: economic impact, lung volumes, CO diffusing capacity, failure risk, whole body plethysmography, MiniBox+&#x2122

Venous thromboembolism is responsible for a significant burden of disease worldwide. Despite the publication of multiple international guidelines, anecdotal evidence suggests significant clinical variation exists in the diagnostic and management pathways of pulmonary embolism (PE). We conducted a retrospective cohort study using electronic medical records to examine clinical variation in patients admitted to a tertiary referral center in Australia with a diagnosis of PE between November 2018 and January 2020. Three hundred cases met the inclusion criteria; we found variation in rates of compression ultrasonography, acute investigation of the right ventricle, and planning of repeat imaging at specialist follow‐up. Guidelines do not address the use of compression ultrasonography in already diagnosed PE, are conflicting in their recommendation for acute investigation of the right ventricle, and recommend repeat imaging only if there are persistent symptoms at the time of specialist follow‐up. The variations we found in this study may in part be due to physician preference or due to the paucity of evidence for some of these diagnostic practices. Robust future studies are required to guide the use of these investigations in PE. [ABSTRACT FROM AUTHOR]

Background: Patients' compliance to inhalation therapy is usually sub-optimal in young asthmatics. Adolescents poorly compliant to regular anti-asthma treatments and those with tattoos (and the associated attitude) can share some personality traits and maladaptive behaviors. This relationship has not been investigated. Objective: To assess if "extended" tattoos can predict long-term compliance to regular therapy of adolescents with mild-to-moderate asthma. Methods: A 12-month retrospective observational investigation was conducted on non-smoker asthmatic adolescents of both genders. Patients assuming <70% of prescribed vilanterol/fluticasone furoate o.d. were defined as "non-compliant". Tattoo surfaces were defined as "mild" or "extended" if they were < or ≥400 cm2, respectively. The relationship between tattoos and compliance on the evolution of resources consumption at 6 and 12 months was assessed by generalized estimating equation (GEE) models at the first and second semester of the treatment period. Results: It was found that 13.2% of compliant adolescents had mild tattoos, while 47.2% of non-compliant adolescents had mild-to-extended tattoos (odds ratio (OR) 6.91, 95% CI 2.49 to 19.17, p < 0.001). The mean annual adherence to treatment was 57.8% ± 10.1 SD expected doses in non-compliant subjects with "mild tattoos" (54.8 cm2 ± 36.9 SD), but 38.6% ± 11.4 SD expected doses in those with "extended tattoos" (568.4 cm2 ± 111.6 SD, p < 0.001). Total cost proved to be a linear trend from the lowest values of compliant patients with no/mild tattoos (EUR 65.22 at 6 months and EUR 33.63 at 12 months) to the highest values of non-compliant adolescents with extended tattoos (EUR 330.75 at 6 months and EUR 297.34 at 12 months). Conclusions: Tattoo extension might be used as a reliable predictor of poor compliance and higher health care costs in adolescents with mild-to-moderate asthma. Patients characterized by poor compliance to a long-term therapeutic strategy and tattooing attitude likely share some aspects of their personality profile. [ABSTRACT FROM AUTHOR]

Abstract Background Dexterity impairments caused by carpal tunnel syndrome (CTS) make working and daily activities challenging. We aimed to investigate: i) the relationship between dexterity and nerve conduction studies (NCS) in workers with classic symptoms presentation; ii) the ability of the Functional Dexterity Test (FDT) to discriminate different levels of CTS severity as classified by NCS; iii) the diagnostic accuracy of a clinical battery composed of the FDT, Phalen’s test and Tinel’s sign. Methods In a convenience sample of individuals diagnosed with CTS, we correlated FDT net scores with the NCS-based classification by means of Spearman’s (rho) test. Discriminative ability of the FDT was assessed by ANOVA, and a ROC curve determined cutoff thresholds. Sensitivity, specificity, and likelihood ratios (LRs) were used to investigate the diagnostic accuracy of the clinical battery. Results Data from 180 hands were collected. The FDT was significantly correlated (rho = 0.25, p

In this paper, we develop a deep learning approach for the accurate solution of challenging problems of near-field microscopy that leverages the powerful framework of physics-informed neural networks (PINNs) for the inversion of the complex optical parameters of nanostructured environments. Specifically, we show that PINNs can be flexibly designed based on full-vector Maxwell’s equations to inversely retrieve the spatial distributions of the complex electric permittivity and magnetic permeability of unknown scattering objects in the resonance regime from near-field data. Moreover, we demonstrate that PINNs achieve excellent convergence to the true material parameters under both plane wave and point source (localized) excitations, enabling parameter retrieval in scanning near-field optical microscopy. Our method is computationally efficient compared to traditional data-driven deep learning approaches as it requires only a single dataset for training. Furthermore, we develop and successfully demonstrate adaptive PINNs with trainable loss weights that largely improve the accuracy of the inverse reconstruction for high-index materials compared to standard PINNs. Finally, we demonstrate the full potential of our approach by retrieving the space-dependent permittivity of a three-dimensional unknown object from near-field data. The presented framework paves the way to the development of a computationally driven, accurate, and non-invasive platform for the simultaneous retrieval of the electric and magnetic parameters of resonant nanostructures from measured optical images, with applications to biomedical imaging, optical remote sensing, and characterization of metamaterial devices.

Bronchial asthma has a high socio-economic impact in Western countries. Low adherence to prescribed inhalation treatments contributes to poor asthma control and the higher utilization of healthcare resources. Although adolescents usually do not comply with long-term inhaled treatments prescribed on a regular basis, the related economic consequences still are poorly investigated in Italy. Aim: A 12-month estimation of the economic impact of non-adherence to inhalation treatments in adolescents with mild-to-moderate atopic asthma. Methods: Non-smoking adolescents aged 12–19 years, without any significant comorbidity, prescribed with inhaled cortico-steroids (ICS) or ICS/long-acting beta(2)-adrenergics (LABA) via dry powder inhalers (DPIs) on a regular basis were automatically selected from the institutional database. Spirometric lung function, clinical outcomes, and pharmacological information were collected. The adolescents’ adherence to their prescribed regimen was calculated monthly. Adolescents were divided in two sub-groups based on their adherence to prescriptions: ≤70% (not adherent) or >70% (adherent), and statistically compared (Wilcoxon test, assuming p < 0.05). Results: Overall, 155 adolescents fulfilled the inclusion criteria (males, 49.0%; mean age, 15.6 years ± 2.9 SD; mean BMI, 19.1 ± 1.3 SD). Mean values of lung function were: FEV1 = 84.9% pred. ± 14.8 SD, FEV1/FVC = 87.9 ± 12.5 SD; MMEF = 74.8% pred. ± 15.1 SD and V25 = 68.4% pred. ± 14.9 SD. ICS had been prescribed in 57.4% of subjects and ICS/LABA in 42.6%. Mean adherence to original prescriptions was 46.6% ± 9.2 SD in non-adherent and 80.3% ± 6.6 SD in adherent adolescents, respectively (p < 0.001). The mean rates of hospitalizations, exacerbations, and GP visits; the average duration of absenteeism; the frequency of systemic steroids and antibiotics courses needed over the study period were significantly and substantially lower in adolescents adherent to prescriptions (all p < 0.001). The mean total annual extra cost calculated in the two sub-groups was EUR 705.8 ± 420.9 SD in non-adherent adolescents and EUR 192.1 ± 68.1 SD in adherent adolescents, respectively (p < 0.001), which was 3.7 times higher than in non-adherent adolescents. Conclusions: In adolescents, the clinical control of mild-to-moderate atopic asthma is directly and strictly related to the degree of adherence to prescribed inhalation therapies. All clinical and economic outcomes prove dramatically poor when adherence is low, and treatable asthma can be frequently mistaken for refractory asthma in these cases. Adolescents’ non-adherence impacts the burden of the disease quite substantially. Much more effective strategies centered specifically on adolescents’ asthma are needed.

Peter MA Calverley,1 Clive Page,2 Roberto W Dal Negro,3 Giovanni Fontana,4 Mario Cazzola,5 Arrigo F Cicero,6 Edoardo Pozzi7,†, Jadwiga A Wedzicha8 1Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK; 2Faculty of Life Sciences and Medicine, King’s College, London, UK; 3Lung Unit, National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 4Pulmonology Department, Cough Centre, Careggi University Hospital, Firenze, Italy; 5Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome ‘Tor Vergata’, Rome, Italy; 6Medical and Surgical Department, University of Bologna, Bologna, Italy; 7Medical Affairs Department, Edmond Pharma, Paderno, Italy; 8Respiratory Division, National Heart And Lung Institute, Imperial College London, London, UK†Dr Pozzii passed away on 9th July, 2019Correspondence: Peter MA CalverleyDepartment of Medicine, University Hospital Aintree, Lower Lane, Liverpool, Merseyside, UKTel +44 1515295886Fax +44 1515295888Email pmacal@liverpool.ac.ukBackground: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine – a muco-active antioxidant that modulates bacterial adhesiveness – reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear.Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann–Whitney U-tests, or log rank tests.Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P=0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P

Abstract Introduction Inhalation devices affect both the effectiveness and the therapeutic outcomes in persistent airway obstruction, and the effects are largely independent of the drug(s) assumed. Usability is a complex and comprehensive indicator of inhalation devices’ performance. The Global Usability Score (GUS) Questionnaire is an investigational tool designed to assess objectively the patients’-related and unrelated domains of devices’ usability. Methods The GUS questionnaire was administered to all consecutive COPD patients referring for three months to the Lung Unit of CEMS Specialist Centre (Verona, Italy). The usability of seven Dry Powder Inhalers (DPIs) indicated as appropriate in COPD was tested and compared: Breezhaler, Diskus, Ellipta, Genuair, Nexthaler, Spiromax, and Turbohaler. Patients were divided in two groups, checked separately, according to their DPIs previous experience. A Bayesian Indirect Comparison (IC) model was built to assess “global usability” ranking. Results A total of 103 patients were investigated: 74 patients already instructed in DPI use and 29 naive to DPIs. IC analysis proved Ellipta as the device characterized by the highest usability, while Breezhaler the device with the lowest usability in both groups of COPD patients (both with probability > 90%). Moreover, Turbohaler ranked second according to the Bayesian pooling, followed by Diskus, Spiromax, Nexthaler, and Genuair in patients already instructed in DPI use, while the ranking order was not as much well defined in naïve patients, likely due to their too small sample. Conclusions Usability is a multifaceted indicator that contributes to assess the factual DPIs’ convenience in real life. DPIs are characterized by different levels of real-life usability, which can be checked, compared and ranked by means of the GUS score.

Abstract 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.

Adolescents with asthma are usually insufficiently adherent to regular inhalation treatments, thus limiting their effectiveness. The aim of this study is to investigate the role of adherence to single-inhaler long-acting LABA/ICS dry-powder combination o.d. in affecting lung function, bronchial hyperreactivity, and health outcomes over a twelve-month survey of a group of non-smoking adolescents with mild to moderate asthma. Methods: Age, gender, BMI and atopy, forced expiratory volume in 1 s (FEV1), maximum mid-expiratory flow (MMEF), and maximum expiratory flow at 25% of lung filling (MEF25) were assessed via a Boolean selection process from the institutional database at recruitment, as well as after 6 and 12 months, together with the incidence of exacerbation, school days that were taken off, GP and specialist visits, and systemic steroid and/or antibiotic courses. Adherence was checked monthly via a direct telephone call. Statistics were calculated with an ANOVA trend analysis, assuming p < 0.05. Results: Two well-matched sample groups of 54 subjects each were obtained. The mean annual adherence to treatment ranged from 48.2% doses ± 10.9 sd to 79.3% doses ± 8.8 sd (p < 0.001), regardless of age and gender. Only adolescents that adhered to the o.d. ICS/LABA inhalation regimen progressively achieved complete control of all lung function parameters (FEV1: 0.001; MMEF: p < 0.002; MEF25 < 0.001; p < 0.001), and optimized all health outcomes (p < 0.001—p < 0.002) over the survey duration. Discussion: A good adherence to treatment is essential for asthma management, particularly in young patients. Factors that are totally independent of the complexity of the therapeutic regimen adopted (namely, only a once-daily inhalation in the present survey) probably represent the major reasons limiting the adolescents’ adherence. Cultural, educational, behavioral, and psychological factors are frequently involved, are difficult to control, and can present barriers to adolescents’ asthma management. Further studies aiming to deeply understand and possibly remove the reasons for such adolescents’ attitudes are needed, in cooperation with actions oriented in this direction by families, educators, and health professionals.

In this paper, we study the wave transport and localization properties of novel aperiodic structures that manifest the intrinsic complexity of prime number distributions in imaginary quadratic fields. In particular, we address structure-property relationships and wave scattering through the prime elements of the nine imaginary quadratic fields (i.e., of their associated rings of integers) with class number one, which are unique factorization domains (UFDs). Our theoretical analysis combines the rigorous Green’s matrix solution of the multiple scattering problem with the interdisciplinary methods of spatial statistics and graph theory analysis of point patterns to unveil the relevant structural properties that produce wave localization effects. The onset of a Delocalization-Localization Transition (DLT) is demonstrated by a comprehensive study of the spectral properties of the Green’s matrix and the Thouless number as a function of their optical density. Furthermore, we employ Multifractal Detrended Fluctuation Analysis (MDFA) to establish the multifractal scaling of the local density of states in these complex structures and we discover a direct connection between localization, multifractality, and graph connectivity properties. Finally, we use a semi-classical approach to demonstrate and characterize the strong coupling regime of quantum emitters embedded in these novel aperiodic environments. Our study provides access to engineering design rules for the fabrication of novel and more efficient classical and quantum sources as well as photonic devices with enhanced light-matter interaction based on the intrinsic structural complexity of prime numbers in algebraic fields.

Background: Persistent cough is one of the most common conditions affecting quality of life. The aim of this study was to assess people’s beliefs regarding the impact of, and changes in the prevalence of, persistent cough in the Italian general population over a 10-year time period. Methods: Two telephone surveys were conducted in 2006 and 2015, and the answers were compared. In 2015, the same questionnaire was also randomly distributed in paper form to another cohort. Sample sizes were precalculated for their representativeness and comparability (Chi-square test). Results: In total, 1,251 subjects in 2015 and 1,334 in 2006 completed the interviews. The corresponding completion rate for the interviews was 23.0% and 21.8%, respectively; 5,056 individuals completed the paper-form questionnaire. A substantial proportion of respondents stated that persistent cough should be regarded as a disease and not merely as a symptom. This belief increased from 38.8% to 46.4% (p40% of responders willing to pay >€10 at the pharmacy in 2015. Conclusion: These surveys showed the prevalence of persistent cough is increasing, together with the willingness of the patient to pay out of their own pocket for treatment. However, the methodology for data collection should be carefully considered before data are generalised.

Jean Bourbeau,1 Denis Granados,2 Stéphane Roze,3 Isabelle Durand-Zaleski,4 Pere Casan,5 Dieter Köhler,6 Silvia Tognella,7 Jose Luis Viejo,8 Roberto W Dal Negro,9 Romain Kessler10 1Department of Medicine, Division of Experimental Medicine, Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 2Medical R&D – Real World & Clinical Evidence, Air Liquide Santé International, Gentilly, France; 3Department of Health Economics, HEVA HEOR, Lyon, France; 4URCEco Ile de France Hôpital de l’Hotel Dieu, Paris, France; 5Department of Pneumology, Asturias University Hospital, Oviedo, Spain; 6Department of Internal Medicine, Kloster Grafschaft Specialised Hospital, Schmallenberg, Germany; 7Department of Pneumology, Bussolengo General Hospital, Bussolengo, Italy; 8Department of Pneumology, Burgos University Hospital, Burgos, Spain; 9Department of Pneumology, Bussolengo Hospital, Bussolengo, Italy; 10Department of Pneumology, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France Purpose: Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET). Methods: Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores. Results: Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR -37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR -806 per patient per year) and Spain (EUR -51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany. Conclusion: Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers. Keywords: cost-effectiveness, France, Spain, Germany, home-based disease management, COPD

A lower thirst sensitivity frequently characterizes children and adolescents. The daily water intake can be frequently insufficient for the homeostasis and the integrity of their airway epithelium. Little is known about the real-life relationship between dehydration and coughing in young students with asthma. The aim was to investigate the effect of dehydration on coughing in asthmatic students aged ≤16 years. A validated questionnaire aimed to investigate their respiratory history and cough incidence was used. Urine samples were also collected for assessing osmolality. Wilcoxon test, the Pearson Chi Square and the Fisher Exact Test were used; p < 0.05 was assumed as significant. Valid data were obtained from 305 healthy and 56 asthmatic students. Mean urine osmolality was significantly higher in asthmatic than in healthy students (1012 ± 197.7 vs. 863.0 ± 223.0 mOsm/kg, respectively; p < 0.001), particularly in symptomatic asthmatic students (1025 ± 191.6 mOsm/kg, p < 0.01). Both the incidence and duration of coughing episodes were directly related to the degree of urine osmolality (both p < 0.001). Dehydration affects the prevalence and the duration of a cough in asthmatic students aged ≤16 years. Adequate daily water intake should be stimulated in these subjects in order to contain their basic cough attitude.

Roberto W Dal Negro,1 Paola Turco,2 Massimiliano Povero3 1National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 2Research & Clinical Governance, Verona, Italy; 3AdRes Health Economics and Outcome Research, Torino, Italy Objectives: Acute cough is the most common symptom among children in primary care, but the economic impact of cough episodes has never been investigated in Italian families.Materials and methods: A cross-sectional telephone survey was conducted on a representative sample of Italian families, randomly selected from general population. Collected data were analyzed to evaluate the economic impact of cough episodes according to, first, Italian Family Perspective and, second, National Health System Perspective (NHS-P). The costs considered in the analysis were the cost of drugs used (antibiotics, corticosteroids, antitussive drugs, and aerosol therapy) and the cost of child care during nursery/school absenteeism.Results: Six hundred four valid questionnaires were analyzed: mean age of children is 7 years (SD=3.3) and that of parents is 40 years (SD=6.2). Mean rate of cough episodes was 3.15/year, and in general, they were short lasting (94.6%, €30 in 19.7% of cases). The overall economic impact on Italian families was estimated as €1,204 (SD=€88); it resulted in a cost per cough episode equal to €337, mainly due to nursery/school absenteeism (94.6%), whereas pharmaceutical expenditure was marginal (5.4%).Conclusion: Cough episodes are acute (lasting

Abstract 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.

Abstract Background Bronchial asthma is an inflammatory disease of the airways. Beclomethasone dipropionate/Formoterol (BDP/F) and Fluticasone furoate/Vilanterol (FF/V) are two of the most effective LABA/ICS combinations for managing persistent bronchial asthma. Aim of the study was to compare the outcomes achieved in mild-to-moderate asthma patients assuming BDP/F 100/6 μg b.i.d. (Group A) or FF/V 92/22 μg once-daily (Group B) for 12-months. No head-to-head long-term comparison is available at present. Methods Data were automatically and anonymously obtained from the institutional database: FEV1% predicted values; the exacerbation and hospitalization rates; days of hospitalization; GP and/or specialist visits; days of inactivity; courses of systemic steroids and/or antibiotics were recorded at baseline and after 3, 6 and 12 months of both treatments. The overall adherence to treatments was also calculated. The propensity score method was used for matching and comparing the two cohorts of patients; Anova and Wilcoxon tests were used for checking the trends and time-to-time comparisons over the period; statistical significance was accepted for p

Several factors affect drug delivery from dry powder inhalers (DPIs). Some are related to patient’s physiological characteristics, while others depend on DPIs’ technical aspects. The patient’s inspiratory airflow rate (IAR) affects the pressure drop and the turbulence needed to disaggregate the powder inside a DPI. The present study investigated whether lung function limitations occurring in asthmatic adolescents affect their IAR when inhaling through a DPI simulator. Eighteen consecutive adolescents with asthma were recruited, and IAR was randomly assessed at low-, mid-, and high-resistance regimens. A multiple logistic model was developed to evaluate the association of patients’ lung function characteristics and devices’ resistance with the probability to achieve the expected IAR (E-IAR). The mean value of E-IAR achieved seemed to be sex- and age-independent. Low- and high-resistance regimens were less likely to consent the E-IAR level (odds ratio [OR] = 0.035 and OR = 0.004, respectively). Only the basal residual volume and the inspiratory resistance, but not the Forced Expiratory Volume in 1 s (FEV1), seemed to affect the extent of IAR in asthmatic adolescents (OR = 1.131 and OR = 0.290, respectively). The results suggest that the assessment of current lung function is crucial for choosing the proper DPI for asthmatic adolescents.