Enrico Heffler

Enrico Heffler
Humanitas University · Biomedical Sciences

MD, PhD

About

312
Publications
77,528
Reads
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5,136
Citations
Additional affiliations
March 2020 - present
Humanitas University
Position
  • Professor (Associate)
Description
  • Associate Professor in Internal Medicine
May 2017 - February 2020
Humanitas University
Position
  • Professor (Assistant)
Description
  • Assistant Professor in Respiratory Medicine
March 2015 - April 2017
University of Catania
Position
  • Professor (Assistant)
Description
  • Assistant Professor in Respiratory Medicine
Education
June 2010 - February 2014
Università degli Studi di Torino
Field of study
  • Experimental Medicine and Therapy
September 2006 - February 2007
University Hospitals Of Leicester NHS Trust
Field of study
  • European Respiratory Society (ERS) Long-Term Research Fellowship
January 2004 - December 2008
Università degli Studi di Torino
Field of study
  • Allergy and Clinical Immunology

Publications

Publications (312)
Article
Background: Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non-invasive biomarkers may facilitate diagnosis and treatment. Recently Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammatio...
Article
Background Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are chronic type 2 inflammatory diseases that are frequently associated with each other. Dupilumab inhibits the dual signaling pathways of interleukin (IL)-4 and IL-13, which are key and central drivers of type 2 inflammation in CRSwNP. Omalizumab blocks the action of immunoglo...
Article
Asthma is one of the most common noncommunicable diseases; in the majority of patients it is well controlled with inhaled bronchodilators and inhaled corticosteroids, but the management of severe asthma has been a significant challenge historically. The introduction of novel biologic drugs in the past few decades has revolutionised the field, prese...
Article
Introduction: : The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. Areas covered: : We reviewed major pa...
Article
Patients with asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, increasing disease burden and complicating treatment. These post hoc analyses investigated disease-specific health-related quality of life (HRQoL) and general health status in the randomized, placebo-controlled QUEST study (NCT02414854) in patie...
Article
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Background: Comorbidities are common in chronic inflammatory conditions, requiring multidisciplinary treatment approach. Understanding the link between a single disease and its comorbidities is important for appropriate treatment and management. We evaluate the ability of an NLP-based process for knowledge discovery to detect information about pat...
Article
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Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy p...
Article
Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for pati...
Article
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Background Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effe...
Article
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Allergic diseases are particularly suitable for personalized medicine, because they meet the needs for therapeutic success, which include a known molecular mechanism of the disease, a diagnostic tool for that disease and a treatment that blocks this mechanism. A range of tools is available for personalized allergy diagnosis, including molecular dia...
Article
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Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized...
Preprint
Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction....
Article
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Nasal cytology is a diagnostic tool that can be used in precision rhinology medicine. Particularly in non-allergic rhinitis and chronic rhinosinusitis forms it can be useful to evaluate biomarkers of both surgical or biological therapy and especially in the follow-up it must be used to predict the prognostic index of recurrence of nasal polyposis....
Preprint
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Humans inhale, ingest and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom are in sharp contrast with their complex and relatively blurred taxonomy and scarce knowledge about their distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview...
Article
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Interleukins (IL)-4 and -13 play a pivotal role in the pathobiology of type-2 asthma. Indeed, IL-4 is crucially involved in Th2 cell differentiation, immunoglobulin (Ig) class switching and eosinophil trafficking. IL-13 cooperates with IL-4 in promoting IgE synthesis, and also induces nitric oxide (NO) production, goblet cell metaplasia and fibrobl...
Article
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Allergen immunotherapy (AIT) and venom immunotherapy (VIT) are meant to work on the causes of allergies, respectively, to respiratory allergens and Hymenoptera venom, inducing tolerance to the allergens and modifying the natural history of allergy. Both types of immunotherapies have evidence of efficacy, but actually they present wide differences i...
Article
Gut microbiota composition of the first stool after birth and the development of allergic diseases before four years of age were investigated in a population‐based cohort study of 212 infants. Atopic and allergic diseases were evaluated at 4 years of age and outcome data was available for 177 (83%) of the children. Meconium microbiota composition,...
Article
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To date, no disease-specific tool has been available to assess the impact of chronic rhinosinusitis with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). Therefore, the purpose of this study was to develop and validate a questionnaire specifically designed to this aim: the Nasal Polyposis Quality of Life (NPQ) questionnaire. As indi...
Technical Report
Full-text available
La rinite allergica è un problema sanitario globale che colpisce dal 5 al 35 % della popolazione. •La sua prevalenza è tendenzialmente in aumento. •Pur non essendo sempre una malattia grave, la rinite influisce sulla vita sociale ed altera le prestazioni scolastiche e lavorative. •I costi socio sanitari sono rilevanti. •La rinite si associa spesso...
Article
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Introduction: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased...
Article
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Background The COVID-19 pandemic has affected health care systems unexpectedly. However, data focusing on practical considerations experienced by health care professionals (HCPs) providing care to allergic patients is scarce. Methods Under the framework of the European Academy of Allergy and Clinical Immunology (EAACI), a panel of experts in the f...
Article
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Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications...
Article
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BACKGROUND Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. OBJECTIVE To compare global differences in ease-of-access to biologics. METHODS In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab,...
Article
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Background Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of...
Article
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Objectives/Hypothesis Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/ob...
Article
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Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labelling 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 allerge...
Article
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Introduction There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in havin...
Article
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Introduction: Type 2-high severe asthma (T2-SA) is often associated with several comorbidities. To this extent, the coexistence of T2-SA and bronchiectasis (BE) is considered an emerging phenotype. Methods: We performed a prospective observational multicentre study, including T2-SA patients. Chest HRCT confirmed the presence of BE. Data on exace...
Article
Giorgio Walter (simply "Walter") Canonica is one of the best-known Allergologists/Pulmunologists in the world. This since his major scientific contributions to the field, but also from his great capability of communicating science, together with his uncommon humanity and open mind. During the past 25 years, Walter has been a major influencer in All...
Article
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In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assesse...
Article
Background Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). Objective We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. Methods The phase 3 OSTRO study enrolled patients with s...
Article
BACKGROUND: Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreedupon super-responder (SR) definition. OBJECTIVE: To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of...
Article
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Allergen immunotherapy (AIT), the gradually increasing repeated administration of high doses of allergens to allergic patients, offers the potential for immune tolerance against reactions to the natural exposures to specific allergens. AIT may lead to the long-lasting remission of allergic symptoms and is the only disease-modifying intervention in...
Article
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Background Observational comparative effectiveness studies in allergen immunotherapy (AIT) represent an important evidence source answering research questions that can be challenging to obtain from randomized controlled trials (RCTs), such as long-term benefits of AIT, the effects on asthma prevention and the onset of new allergen sensitizations. H...
Article
Hintergrund: Die Vision der europäischen allergologischen Gesellschaften ist es, die Ausbildung zum Allergologen in Europa zu vereinheitlichen und prinzipiell den Facharzt für Allergologie zu fordern und zu fördern. In den meisten europäischen Ländern gibt es bereits den Facharzt für Allergologie. In Deutschland gibt es leider nur eine Zusatzbezeic...
Article
Introduction: The SARS-CoV-2 pandemic has deeply revolutionized our lives and consequently the management of patients, specifically ones with severe asthma. Objective: A survey was conducted to evaluate the effects on adherence, exacerbations and quality of life in patients with severe asthma during the COVID-19 pandemic period. Methods: 100 severe...
Article
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BACKGROUND Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been recently approved, and public concern regarding the risk of anaphylactic reactions arised after few cases during the first days of mass-vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions....
Article
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Background Phenotypic characteristics of eosinophilic and non-eosinophilic asthma patients are not well-characterized in global, real life severe asthma cohorts. Research Question What is the prevalence of eosinophilic and non-eosinophilic phenotypes in the severe asthma population, and can they be differentiated by clinical and biomarker variable...
Article
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The large amount of evidence and the renewed interest on upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD). Starting from an extensive literature review, Interasma excecutive committee discussed and approved this Manifesto dev...
Article
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Purpose: After adolescence, asthma is more frequent in females than in males due to different hormonal, immunologic, and occupational/environmental factors. The higher prevalence and severity of the disease in females have already been reported in international registries. The aim of this study was to explore the difference in terms of clinical, f...
Article
The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Eosinophil knockout mice have identified a contribu...
Article
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Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information...
Article
Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or ex...
Article
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Background Although there are reports of otolaryngological symptoms and manifestations of CoronaVirus Disease 19 (COVID-19), there have been no documented cases of sudden neck swelling with rash in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection described in literature. Case presentation We report a case of a s...
Article
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Purpose of review: Gastro-esophageal reflux is a possible cause of uncontrolled symptoms of asthma and should be actively investigated and treated before severe asthma is diagnosed and biological therapy started. Recent findings: Recent investigations on esophageal function and tissue biomarkers in patients with asthma and associated GERD have e...
Article
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Purpose of review: Allergen-specific immunotherapy has established as an indispensable disease-modifying treatment in allergy practice but its safety and efficacy might be furtherly improved by combining it with other drugs or therapeutic intervention that co-modulate immune type 2 immune networks. Recent findings: In the past two decades, clini...
Article
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Background and aims Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods Patients >18 years old, referred to 8...
Article
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CONCLUSIONS: The triple spray decreases AR symptoms by decreasing inflammation and mast cell activities with an addition of the vasoconstrictive property of oxymetazoline. Our preliminary data suggests that the triple spray is an effective AR treatment that offers a statistically significant improvement in management of sinus pressure compared to a...
Article
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BACKGROUND Among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), randomized clinical trials (RCTs) of biologics, such as anti-IL-4/IL-13 (dupilumab) and anti-immunoglobulin E (omalizumab), have demonstrated efficacy versus intranasal corticosteroids (INCS). However, no head-to-head RCTs exist between biologics. OBJECTIVE To perfor...
Article
Background: Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life. Methods: To address the current unmet need for an appraisal of the quality of RWE in...
Article
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Background Italy has been the first non-Asian country affected by Coronavirus Disease 19 (COVID-19) pandemic. Community pharmacies are essential services authorized to continue their activity during the emergency. To date, a clear image is lacking of the critical issues Italian community pharmacists had to face and of how they responded in their da...
Preprint
Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy...
Preprint
Full-text available
La rinosinusite cronica (chronic rhinosinusitis, CRS) con poliposi nasale (chronic rhinosisusitis with nasal polyposis, CRSwNP) è patologia ad elevata prevalenza e ad alti costi sociali [1]. Nonostante sia relativamente facile da diagnosticare, presenta molti “unmet needs” come le scarse conoscenze sull’eziologia, l’associazione con alcuni fenotipi...
Article
Objective Asthma is a frequent comorbidity of bronchiectasis, with possible implications for exacerbation and severity. We investigated the clinical impact of asthma on bronchiectasis in terms of disease severity and exacerbation risk. Methods We collected demographic, clinical, and functional characteristics of patients with a confirmed diagnosis...
Chapter
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La poliposi nasale presenta ancora molti lati oscuri per la classe medica, anche se nell'ultimo decennio la letteratura ha avuto un forte impulso grazie all'evoluzione dell'immunologia clinica. Le infiammazioni delle vie respiratorie sono diventate protagoniste di numerosi studi clinici con farmaci di nuova generazione. Inoltre, il concetto di Medi...
Article
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Purpose of review: The aim of the article is to highlight the association between α1-antitrypsin deficiency (AATD) and asthma. Recent findings: AATD is one of the most common and underrecognized autosomal disorders associated with an increased risk of developing liver and lung diseases. An association between α1-antitrypsin and asthma has been s...
Article
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Background: Almost the entire World is experiencing the Coronavirus-Disease-2019 (COVID-19) pandemic, responsible, at the end of May 2020, of more than five million people infected worldwide and about 350,000 deaths. In this context, a deep reorganization of allergy clinics, in order to ensure proper diagnosis and care despite of social distancing...
Article
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Background: A significant proportion of patients with severe asthma may also suffer from nasal polyposis, which is commonly defined as chronic rhinosinusitis with nasal polyps (CRSwNP), the presence of which may adversely affect asthma treatment outcomes. The biologic agent omalizumab is effective as add-on therapy in patients with severe allergic...