Raw Cow’s Milk Prevents the Development of Airway Inflammation in a Murine House Dust Mite-Induced Asthma Model

Juan Carlos Ivancevich Saturday, 16 September 2017 00:12
 

Abstract

Epidemiological studies show an inverse relation between raw cow’s milk consumption and the development of asthma. This protective effect seems to be abolished by milk processing. However, evidence for a causal relationship is lacking, and direct comparisons between raw and processed milk are hardly studied. Therefore, this study investigated the preventive capacity of raw and heated raw milk on the development of house dust mite (HDM)-induced allergic asthma in mice. Six- to seven-week-old male BALB/c mice were intranasally (i.n.) sensitized with 1 µg HDM or PBS on day 0, followed by an i.n. challenge with 10 µg HDM or PBS on days 7–11. In addition, mice were fed 0.5 mL raw cow’s milk, heated raw cow’s milk, or PBS three times a week throughout the study, starting 1 day before sensitization. On day 14, airway hyperresponsiveness (AHR) in response to increasing doses of methacholine was measured to assess lung function. Bronchoalveolar lavage fluid (BALF) and lungs were furthermore collected to study the extent of airway inflammation. Raw milk prevented both HDM-induced AHR and pulmonary eosinophilic inflammation, whereas heated raw milk did not. Both milk types suppressed the Th2-polarizing chemokine CCL17 in lung homogenates and reduced lung Th2 and Th17 cell frequency. IL-4 and IL-13 production after ex vivo restimulation of lung T cells with HDM was also reduced by both milk types. However, local IL-5 and IL-13 concentrations were only suppressed by raw milk. These findings support the asthma-protective capacity of raw cow’s milk and show the importance of reduced local type 2 cytokine levels. Heated raw milk did not show an asthma-protective effect, which indicates the involvement of heat-sensitive components. Besides causal evidence, this study provides the basis for further mechanistic studies.

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Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies

Juan Carlos Ivancevich Wednesday, 13 September 2017 14:04

Geoffrey ChuppMichel LavioletteLauren CohnCharlene McEvoySandeep BansalAdrian ShifrenSumita KhatriG. Mark GrubbEdmund McMullenRacho StrauvenJoel N. Kline

The Unresolved Role of Interferon-λ in Asthma Bronchiale

Juan Carlos Ivancevich Monday, 04 September 2017 22:10
Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany

Asthma bronchiale is a disease of the airways with increasing incidence, that often begins during infancy. So far, therapeutic options are mainly symptomatic and thus there is an increasing need for better treatment and/or prevention strategies. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and might cause acute wheezing associated with local production of pro-inflammatory mediators resulting in neutrophilic inflammatory response. Viral infections induce a characteristic activation of immune response, e.g., TLR3, 4, 7, 8, 9 in the endosome and their downstream targets, especially MyD88. Moreover, other cytoplasmic pattern recognition molecules (PRMs) like RIG1 and MDA5 play important roles in the activation of interferons (IFNs) of all types. Depending on the stimulation of the different PRMs, the levels of the IFNs induced might differ. Recent studies focused on Type I IFNs in samples from control and asthma patients. However, the administration of type I IFN-α was accompanied by side-effects, thus this possible therapy was abandoned. Type III IFN-λ acts more specifically, as fewer cells express the IFN-λ receptor chain 1. In addition, it has been shown that asthmatic mice treated with recombinant or adenoviral expressed IFN-λ2 (IL–28A) showed an amelioration of symptoms, indicating that treatment with IFN-λ might be beneficial for asthmatic patients.

 
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Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma

Juan Carlos Ivancevich Wednesday, 06 September 2017 13:19

REVIEW ARTICLE

Front. Med., 31 August 2017 | https://doi.org/10.3389/fmed.2017.00135
imageDiego Bagnasco1, imageMatteo Ferrando1, imageGilda Varricchi2, imageFrancesca Puggioni3, imageGiovanni Passalacqua1 and imageGiorgio Walter Canonica1,3*
1Allergy and Respiratory Diseases, DIMI Department of Internal Medicine, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy
2Department of Translational Medical Sciences, Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy
3Department of Internal Medicine, Respiratory Disease Clinic, IRCCS Humanitas Clinical and Research Center, Humanitas University, Milan, Italy

The definition of asthma has changed considerably in recent years, to the extent that asthma is no longer considered a single disease but a heterogeneous disorder that includes several phenotypes and, possibly, endotypes. A more detailed analysis of the immunological mechanisms underlying the pathogenesis of asthma shows interleukin 5 (IL-5) to be a crucial cytokine in several asthma phenotypes. In fact, IL-5 exerts selective action on eosinophils, which, in turn, sustain airway inflammation and worsen asthma symptoms and control. Clinical trials have shown drugs targeting IL-5 or its receptor alpha subunit (IL-5Ra) to be a promising therapeutic approach to severe asthma, whose characteristics render standard therapy of little use: systemic corticosteroids only partially control the disease and have well-known adverse effects, and omalizumab is used for allergic subtypes. Analysis of the design process of clinical trials reveals the importance of patient selection, taking into account both clinical data (e.g., exacerbations, lung function, and quality of life) and biomarkers (e.g., eosinophils, which are predictive of therapeutic response).

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Asthma management among allergists in Italy: results from a survey

Juan Carlos Ivancevich Saturday, 26 August 2017 21:54

https://doi.org/10.1186/s12948-017-0067-2

M. S. Magnoni, M. Caminati, G. W. Canonica, F. Arpinelli, A. Rizzi and G. Senna

Abstract

Background

In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy.

Aims and objectives

The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management.

Methods

An anonymous 16 item web questionnaire was available (April–October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy.

Results

One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence.

Conclusions

Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

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Editor: Juan C. Ivancevich, MD

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