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Giovanni Rolla Department of Medical Sciences, University of Torino, Torino, ItalyCorrespondence: Giovanni Rolla, Email giovanni.rolla@unito.itAbstract: Asthma continues to be a disease for which there is no cure, even if it can be very well controlled with the appropriate therapies, which take into account the specific phenotype. The paradox of asthma is that asthma can heal spontaneously, albeit in a small percentage of cases. This observation is highly relevant, since understanding the mechanisms of spontaneous healing can pave the way for new strategies for treating asthma. It is likely that the lack of cure for asthma is due to the fact that current therapies target downstream mediators of the inflammatory response. Asthma can be considered a response of maladaptation of the airway epithelium to the environment, through the orientation of the innate immunity towards an inflammatory response. The important effect of the environment on asthma progress comes from interventions which help children who live in disadvantaged urban neighborhoods move to higher resourced neighborhoods. It is quite interesting that the magnitude of decrease of exacerbations associated with moving was larger than the effect of inhaled corticosteroids and similar to that observed for the effect of biologic agents. Alpine altitude climate treatment is a natural treatment that targets biological pathway, improving various outcomes such as asthma control and quality of life, exacerbation rate and hospitalizations. If as researchers we want to set ourselves the goal of achieving complete remission of asthma, without the need for ongoing maintenance treatment, we need to change the approach to finding new asthma treatment strategies. The One Health approach, an interdisciplinary strategy with focal point on human, animal, and environmental health interconnections, appears to be the right tool for researching asthma prevention and treatment.Keywords: asthma, environment, alpine treatment, one health

Background: Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry. Methods: The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication. Results: Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%.Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown. Conclusions: Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs. Keywords: Severe asthma, Oral corticosteroids, Adverse events, Pharmacoeconomy, Costs, Diabetes, Glaucoma, Obesity, Bone fracture, Chronic kidney disease

Luisa Brussino,1 Paolo Solidoro,2 Giovanni Rolla1 1Allergy and Clinical Immunology, University of Torino and Mauriziano Hospital, 2SC Pneumologia U, AOU Città della Salute e della Scienza, Torino, Italy Abstract: Severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids (ICSs) plus a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy. This definition has limitations: 1) it does not define any biological characteristic that distinguishes severe asthma from asthma in general and 2) it relies on the clinical interpretation of asthma symptoms that are not specific. Actually, wheezing, dyspnea, cough and chest tightness may be caused by the comorbidities (such as rhinosinusitis, obesity and vocal cord dysfunction [VCD]) which are associated with asthma. In clinical practice, clinicians are often prone to diagnose uncontrolled asthma and increase doses of ICSs without considering the comorbidities, resulting in poor control of symptoms. This commentary wishes the clinicians to focus on the comorbidities of asthma, particularly in patients with severe asthma, because the correct diagnosis of these comorbidities implies specific treatments that lead to a better asthma control. Keywords: severe asthma, chronic rhinosinusitis, obesity, vocal cord dysfunction, dupilumab

Abstract Background Complete tooth loss (edentulism) produces anatomical changes that may impair upper airway size and function. The aim of this study was to evaluate whether edentulism favours the occurrence of obstructive sleep apnoea (OSA). Methods Polysomnography was performed in 48 edentulous subjects on two consecutive nights, one slept with and the other without dentures. Upper airway size was assessed by cephalometry and by recording forced mid-inspiratory airflow rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as markers of airway and oropharyngeal inflammation. Results The apnoea/hypopnoea index (AHI) without dentures was significantly higher than with dentures (17·4 ± 3·6 versus 11·0 ± 2·3. p = 0·002), and was inversely related to FIF50 (p = 0·017) and directly related to eNO (p = 0·042). Sleeping with dentures, 23 subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without dentures the number of subjects with abnormal AHI rose to 34 (71%). At cephalometry, removing dentures produced a significant decrease in retropharyngeal space (from 1·522 ± 0·33 cm to 1·27 ± 0·42 cm, p = 0·006). Both morning eNO and oNO were higher after the night slept without dentures (eNO 46·1 ± 8·2 ppb versus 33·7 ± 6·3 ppb, p = 0·035, oNO 84·6 ± 13·7 ppb versus 59·2 ± 17·4 ppb, p = 0·001). Conclusion These findings suggest that complete tooth loss favours upper airway obstruction during sleep. This untoward effect seems to be due to decrease in retropharyngeal space and is associated with increased oral and exhaled NO concentration.

In the present study supragingival dental calculus of unknown age was collected from the mandibular incisors of three individuals and solubilized by EDTA. The extracts were examined by gel filtration, ionic exchange chromatography and amino acid analysis. A protein component with similar characteristics to the main protein component of the acquired enamel pellicle was a regular constituent of the calculus extracts from the three subjects. [ABSTRACT FROM AUTHOR]

The present study showed that the growth of Streptococcus mutans strain GS5 was inhibited by xylitol, and this indicates together with previous reports that this is a common phenomenon in this species. Sorbitol was found to increase the growth of S. mutans strains OMZ 176 and GS5 slightly compared with cultures with no external carbon source. Addition, of small amounts of xylitol to the sorbitol cultures gave a growth below that of cultures with no extra carbon. Dental plaque challenged with sorbitol gave a small pH drop whereas xylitol caused a negligible decrease in pH. Sorbitol-xylitol challenges gave less acid production than sorbitol challenges alone. [ABSTRACT FROM AUTHOR]

Lipoteichoic acid extracted from cells of S. mutans strain BHT exhibited a high affinity for hydroxyapatite. Phosphate ions, fluoride ions and to a lesser extent human saliva inhibited or reversed this adsorption. Extracellular lipoteichoic acid preparations obtained from the supernatant of cultures of the same bacteria exhibited similar properties. It is suggested that lipoteichoic acids could play a significant role in the colonization of teeth by Gram-positive bacteria and thereby contribute to the formation and pathogenicity of dental plaque. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the inhibition of dental plaque by chlorhexidine. An in vitro investigation of the interaction of chlorhexidine with carboxyl, sulfate, and phosphate groups is presented, noting the factors that could interfere with the process. A comparison is made with the properties of cetylpyridine in the same interactive relationships. Also examined are the chlorhexidine-binding properties of extracts from the proteins found within saliva originating from the major salivary glands at various hydrogen-ion concentrations (pH levels).

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