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Alessandro Fiocchi

    Alessandro Fiocchi

    Nasal polyps (NPs) are rarely reported in childhood and usually represent red flags for systemic diseases, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and immunodeficiencies. The European Position Paper released in 2020... more
    Nasal polyps (NPs) are rarely reported in childhood and usually represent red flags for systemic diseases, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and immunodeficiencies. The European Position Paper released in 2020 (EPOS 2020) provided a detailed classification and defined the correct diagnostic and therapeutic approaches. We report a one-year experience of a multidisciplinary team, made up of otorhinolaryngologists, allergists, pediatricians, pneumologists and geneticists, with the aim of ensuring a personalized diagnostic and therapeutic management of the pathology. In 16 months of activity, 53 patients were admitted (25 children with chronic rhinosinusitis with polyposis and 28 with antro-choanal polyp). All patients underwent phenotypic and endo-typic assessment, using proper classification tools for nasal pathology (both endoscopic and radiological), as well as adequate cytological definition. An immuno–allergic evaluation was carried out. Pneumologists ...
    Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links... more
    Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always...
    Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of... more
    Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel ap...
    Background Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in... more
    Background Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. Objectives The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. Outcomes Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.
    Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due... more
    Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough.
    Background Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a... more
    Background Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. Objectives The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. Outcomes Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.
    BackgroundAlthough there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be... more
    BackgroundAlthough there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA‐EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases.MethodsA modified Delphi process was used. The ARIA members who were seeing COVID‐19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID‐19, common cold and allergic rhinitis.ResultsAmong the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two‐way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001).ConclusionsThis modified Delphi approach enabled the differentiation of upper respiratory symptoms between COV...
    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented... more
    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or AC...
    In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1... more
    In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV...
    Large differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large... more
    Large differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS‐CoV‐2 binds to its receptor, the angiotensin‐converting enzyme 2 (ACE2). As a result of SARS‐CoV‐2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID‐19. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables co...
    BackgroundIn allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK‐air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome.... more
    BackgroundIn allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK‐air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom‐medication scores obtained concurrently.MethodsAll consecutive MASK‐air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self‐assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom‐medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra‐individual response variability (IRV) index was calculated.ResultsA strong correlation was ob...
    BackgroundIn all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of... more
    BackgroundIn all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main bodyAs an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by phar...
    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The... more
    Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability o...
    BOUSQUET J.; KHALTAEV N.; CRUZ AA; DENBURG J.; FOKKENS W.; TOGIAS A.; ZUBERBIER T.; BAENA-CAGNANI C.; CANONICA GW; VAN WEEL C.; AGACHE I.; AÏT-KHALED N.; BACHERT C.; BLAISS M.; BONINI S.; BOULET L.-P.; BOUSQUET P.-J.; ...
    This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for... more
    This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
    Research Interests:
    Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a... more
    Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient’s serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower...
    BackgroundFood anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products... more
    BackgroundFood anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by high...
    Food allergy (FA) and, in particular, IgE-mediated cow’s milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow’s milk allergic (CMA) infants with that... more
    Food allergy (FA) and, in particular, IgE-mediated cow’s milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow’s milk allergic (CMA) infants with that of cow’s milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifical...
    Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive... more
    Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lami...
    Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital... more
    Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
    Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers... more
    Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacte...
    Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass... more
    Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 ( = 5), 30 ( = 6), 60 ( = 5), and 90 ( = 4) days postpartum), and milk from donkeys ( = 4), cows ( = 4), buffaloes ( = 7), goats ( = 4), ewes ( = 5), and camels ( = 2) were collected. Different brands ( = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-def...
    BackgroundTo date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken.ObjectiveTo review the efficacy and safety of vitamin D supplementation when... more
    BackgroundTo date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken.ObjectiveTo review the efficacy and safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies.MethodsThree databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.ResultsAmong the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis ...
    Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old... more
    Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.
    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of... more
    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support...
    Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of... more
    Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of cow's milk allergy (CMA) in SBS infants. We reviewed three cases of CMA developed in 37 children with neonatal SBS followed up in the last 10 years. The setting of the survey was the Gastroenterology-Hepatology and Nutrition Unit of the Pediatric Hospital 'Bambino Gesù' in Rome. The diagnosis of CMA was based on the oral food challenge and was supported by the results of the skin prick tests (SPT) and/or the specific immunoglobulin (Ig) E. Two patients had persistent liquid stools and periodic episodes of vomiting when they were fed with an intact milk protein-based formula, that disappeared with extensively hydrolyzed formula and amino-acid-based formulae, respectively. The third patient developed maculo-papular rash, flushing and angioedema...
    Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as... more
    Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows separate measurement of CFTR-dependent chloride or bicarbonate transport, was used to assess the effect of ELX/TEZ/IVA on two rare CFTR variants. Methods: Intestinal organoid cultures were established from rectal biopsies of CF patients carrying the rare missense mutations E193K or R334W paired with F508del. The effect of the CFTR modulator combination ELX/TEZ/IVA on CFTR-mediated Cl− and HCO3− secretion was assessed in organoid-derived intesti...

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