Marcello Montagni

Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Anaphylaxis and cardiovascular diseases: a dangerous liaison.

Purpose of reviewAnaphylaxis is a life-threatening event in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. This review summarizes the most recent clinical and experimental data on cardiovascular involvement during anaphylaxis. Recent findingsGreat efforts have been made in the last few years to understand the pathophysiology of anaphylactic reaction and to provide better identification of risk factors for the development of this reaction. Coronary blood flow can be impaired during anaphylaxis, which may significantly contribute to an unfavourable outcome. Also, preexisting coronary artery disease is a negative prognostic factor for anaphylaxis. In addition, acute ischemic events, including angina and myocardial infarction, are currently considered as part of the clinical picture of anaphylaxis. Moreover, cardiac emergency can be the presenting clinical picture of mast cell-related disorders. SummaryBoth cardiovascular and allergic diseases are frequent among populations. A better understanding of the mechanisms leading to cardiac mast cell activation and the effects of mast cell mediators on cardiovascular system can help improve the prevention and treatment of anaphylaxis.

A Pitfall to Avoid When Using an Allergen Microarray: The Incidental Detection of IgE to Unexpected Allergens

The introduction of new laboratory techniques to detect specific IgE antibodies against single allergen molecules rather than whole extracts represents a significant advance in allergy diagnostics. The advantages of such component-resolved diagnosis can be summarized as follows: (1) the ability to identify the truly responsible allergens in polysensitized patients, whether they be genuine (causing specific sensitization to their corresponding allergen source) or primary (the original sensitizing molecule); (2) distinguishing these allergens from simply cross-reactive components; (3) improving the appropriateness of the prescribed specific immunotherapy; and (4) identifying a risk profile for food allergens. Component-resolved diagnosis is performed using either a singleplex (1 assay per sample) platform or a multiplex (multiple assays per sample) platform. Using an immuno solid-phase allergen chip microarray that falls into the latter category--it currently tests sensitivity to 112 allergens--may lead to a pitfall: detecting IgE to unexpected allergens, such as Hymenoptera venom. In fact, testing insect venom sensitivity in individuals with no history of reactions to stings is contrary to current guidelines and presents the physician with the dilemma of how to manage this information; moreover, this may become a legal issue. Based on what is currently known about venom allergy, it remains likely that a positive sensitization test result will have no clinical significance, but the possibility of reacting to a future sting cannot be completely ruled out. Because this problem has not been previously encountered using the more common allergy tests, no indications are currently available on how to effectively manage these cases.

Pharmacotherapy of allergic rhinitis: current options and future perspectives

Introduction: Allergic rhinitis (AR) is a very common disease, caused by environmental aeroallergen, and clinically expressed by sneezing, nasal itching, rhinorrhea and obstruction. It is often considered a mild illness, but actually it has a significant individual and social burden. The management of AR is based on allergen avoidance, pharmacological treatment and allergen specific immunotherapy. Areas covered: In this article, the authors summarize the current status of pharmacotherapy of AR, its possible options and the future perspective. Expert opinion: In most cases of AR, pharmacotherapy must be considered the cornerstone intervention. Particularly, antihistamines and intranasal corticosteroids should be the first-line agents. Other agents to be considered, depending on clinical features in single patients, are systemic corticosteroids, antileukotrienes, anticholinergics, nasal decongestants and mast cell stabilizers. Specific immunotherapy is able to reduce the drugs consumption and was shown to be effective in severe rhinitis uncontrolled with drugs. The future perspective include combination therapy with intranasal antihistamines and corticosteroids, the anti-IgE antibody omalizumab, histamine H3 and H4 receptor antagonists, cytokine inhibitors and toll-like receptors targeted treatment.

Arguing the misconceptions in allergen-specific immunotherapy

Allergen immunotherapy (AIT) has a clear evidence of efficacy and safety, as shown by a number of meta-analyses. However, a number of issues limit the use of AIT, many of them being not actually supported by solid data from the literature. In particular, several contraindications to AIT deserve to be argued, being needed to accurately balance in single cases the benefits versus the disadvantages. This concerns comorbidities, such as autoimmune diseases and malignancies, concomitant drug treatments, particularly β-blockers and angiotensin-converting enzyme inhibitors, pregnancy, patients age, the severity of asthma, allergen polysensitization and the period of starting the treatment. Another important aspect producing misconceptions on AIT is the quality of the allergen extracts, because currently a patient with respiratory allergy to a given source may be prescribed to treat his allergyby products with very different quality. Improving characterization and standardization of allergen extracts will pave the way to the general acknowledgment of AIT as an effective treatment.

Emerging drugs for allergic conjunctivitis

Introduction: Allergic conjunctivitis (AC) is a very common disease, especially in association with allergic rhinitis but may also occur in isolated presentation. The treatment of AC has long been based on antihistamines, cromones and topical corticosteroids, but none of these drugs completely abolishes the clinical expression of AC. Areas covered: The development of new drugs for AC is analyzed highlighting the recent insights into the pathophysiological mechanisms of the disease. The major aim of development of drugs for AC is to have agents able to prevent the inflammatory effects of the interaction between the allergen and the specific IgE antibodies on mast cell surface. This may be obtained by blocking the effects of histamine (the main mediator of early allergic response) by H1-receptor antagonists, inhibiting the release of soluble factors able to recruit inflammatory cells (that sustain prolonged inflammation) by mast-cell stabilizers, inhibiting the effects of single mediators, inducing tolerance to the allergen by specific immunotherapy or even acting on factors related to activation and differentiation of T lymphocytes such as the toll-like receptors. Expert opinion: AC is an underestimated disease for which there is a search of more effective treatments. The availability of the drugs under current evaluation will allow more refined therapeutic strategies to apply according to the characteristics and the clinical severity of AC.

Work-related allergies to storage mites in Parma (Italy) ham workers

Objectives To investigate the role of storage mites in the development of allergic diseases among ham production workers, and to search for early alterations in lung function tests and early inflammation markers in exhaled air. Respiratory allergies due to storage mites have been reported in people with various occupations but, although such mites are unavoidable when curing ham, there are no published data concerning ham production workers. Setting Secondary care. Design Experimental cross-sectional study. Participants 220 participants (110 ham production workers and 110 controls) were recruited. Primary and secondary outcome measures Workers answered a medical questionnaire, and underwent spirometry and fraction of exhaled nitric oxide at 50 mL/s (FeNO50) measurements. Those with allergic symptoms also underwent skin prick tests to determine their sensitisation to airborne allergens. A methacholine test was performed in symptomatic participants when spirometry was normal to assess airways hyper-responsiveness. Results Symptomatic storage mite sensitisation was observed in 16 workers (14.5%) (rhinoconjunctivitis in 15 (63%) and asthma in (4%)) and 2 controls (1.8%; p=0.001). Higher FeNO50 values in exposed symptomatic workers compared with healthy control participants (34.65±7.49 vs 13.29±4.29 ppb; p<0.001) suggested bronchial and nasal involvement, although their lung function parameters were normal. Regardless of exposure, a FeNO50 value of 22.5 ppb seems to be 100% sensitive and 99.4% specific in distinguishing allergic and non-allergic participants. Multivariate analysis of FeNO50 values in the symptomatic participants showed that they were positively influenced by IgE-mediated allergy (p=0.001) and reported symptom severity (p=0.041), and negatively by smoking status (p=0.049). Conclusions Ham processing workers, as well as workers involved in any meat processing work that includes curing, should be informed about the occupational risk of sensitisation to mites.

Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review.

Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far.

Quality of sleep in allergic children and their parents

BACKGROUND Quality of sleep is essential for physical and mental health and influences the perception of the patients well-being during the day. In patients with chronic allergic diseases sleep disorders may increase the severity of the condition, complicate the management and impair their quality of life. When children are concerned, their parents are also affected by the problem. We evaluated the presence of disrupted sleep in parents of children with atopic disorders, and its relationship with clinical features and the presence of disturbed sleep in children. METHODS Parents of children suffering from allergic diseases were recruited from the Pediatric Allergy Units of Parma University. Evaluation of sleep in parents was based on the Pittsburg Sleep Quality Index (PSQI), while in children it was based on the Sleep Disturbance Scale for Children (SDSC). RESULTS Of the 102 parents invited, 92 filled in the questionnaire. Only the questionnaires with more than a 95% completion rate were considered for analysis. PSQI mean score in parents was 6.6 (SD 2.6); 75.6% of them had a PSQI ≥ 5, indicating that most parents had a sleep quality perceived as bad. The PSQI ≥ 5 was more common in parents of children with asthma and rhinitis. In children, SDSC mean score was 42.1 (SD: 9.4); 62.3% had a total score ≥ 39. The quality of sleep in parents and children was significantly correlated (p<0.001). CONCLUSION These findings make it apparent that an alteration of sleep in children can also affect the parents. Such effect further weighs the burden of respiratory allergy and needs to be considered in future studies.

Eosinophilic esophagitis: which role for food and inhalant allergens?

Eosinophilic esophagitis is a chronic inflammatory disease of the esophagus, immune/antigens mediated, whose incidence is increasing both in adults and pediatric population. It is clinically characterised by symptoms related to esophageal dysfunction and associated with eosinophil-predominant esophageal inflammation. The role of atopy has been clearly demonstrated both in epidemiological and experimental studies and has important implications for diagnosis and therapy. In fact, many evidences show that food and inhalant allergens represent the most important factors involved in the progress of the disease. Several studies have reported that, in a range between 50 and 80%, patients with eosinophilic esophagitis have a prior history of atopy, and for them, the presence of allergic rhinitis, asthma or atopic dermatitis is frequent. Skin tests are able to identify in most patients the allergens involved, allowing a correct dietary approach in order to achieve the remission of symptoms and the biopsy normalization.