Maria D'Amato

Environmental risk factors and allergic bronchial asthma.

The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE‐mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant‐derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen‐carrying agents but also their allergenic potential. In addition, by inducing airway inflammation, which increases airway permeability, pollutants overcome the mucosal barrier and could be able to ‘prime’ allergen‐induced responses. There are also observations that a thunderstorm occurring during pollen season can induce severe asthma attacks in pollinosis patients. After rupture by thunderstorm, pollen grains may release part of their cytoplasmic content, including inhalable, allergen‐carrying paucimicronic particles.

Outdoor air pollution, climatic changes and allergic bronchial asthma.

Both the prevalence and severity of respiratory allergic diseases such as bronchial asthma have increased in recent years. Among the factors implicated in this “epidemic” are indoor and outdoor airborne pollutants. Urbanisation with its high levels of vehicle emissions and Westernised lifestyle parallels the increase in respiratory allergy in most industrialised countries, and people who live in urban areas tend to be more affected by the disease than those of rural areas. In atopic subjects, exposure to air pollution increases airway responsiveness to aeroallergens. Pollen is a good model with which to study the interrelationship between air pollution and respiratory allergic diseases. Biological aerosols carrying antigenic proteins, such as pollen grains or plant-derived paucimicronic components, can produce allergic symptoms. By adhering to the surface of these airborne allergenic agents, air pollutants could modify their antigenic properties. Several factors influence this interaction, i.e., type of air pollutant, plant species, nutrient balance, climatic factors, degree of airway sensitisation and hyperresponsiveness of exposed subjects. However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of inhaled allergens to the cells of the immune system, and so promote airway sensitisation. As a consequence, an enhanced immunoglobulin E-mediated response to aeroallergens and enhanced airway inflammation favoured by air pollution could account for the increasing prevalence of allergic respiratory diseases in urban areas.

Clothing is a carrier of cat allergens

Clinical and allergologic studies have shown that sensitization to allergens derived from domestic animals (dogs and particularly cats) is an important cause of prolonged airway hyperresponsiveness with allergic respiratory symptoms and is sometimes a risk factor for bronchial asthma attacks leading to emergency department visits. 1 The major cat allergen, Fel d 1, is found universally in homes of patients with respiratory allergy induced by this animal. Significant increases in allergen levels have been detected after simply allowing the cats to leave their holding cages and move about the room. However, Fel d 1 is also present in dust samples from homes and public places where a cat has never been kept. 2 Consequently, not only direct exposure to cats but also indirect contact may be responsible for an allergic sensitization. In fact, many patients who are allergic to cats do not have this animal in their homes. In this trial, to determine whether clothing could be responsible for dispersal of cat allergen, concentrations of Fel d 1 have been quantified in dust samples from clothes of subjects with and without a cat or a dog in their homes.

Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patients existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking. OBJECTIVE The aim of the study was to compare the inhaled beta2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II). METHODS A dose-response curve to formoterol via Turbuhaler or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 microg formoterol via Turbuhaler (48-microg cumulative metered dose); B = 200 + 200 + 400 microg salbutamol via pMDI (800-microg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded. RESULTS Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV1, inspiratory capacity (IC), and forced vital ca- pacity (FVC). There was no significant difference between FEV1, IC, and FVC values after 48 microg formoterol and 800 microg salbutamol. There was no significant difference in FEV1 after 24 microg formoterol and 800 microg salbutamol; however, the difference in FEV1 after 24 and 48 microg formoterol was significant. Neither heart rate (mean differences from baseline after 48 microg formoterol, 1.9 beats/min [95% CI, -3.4, 7.2] and 800 microg salbutamol, 3.7 beats/min [95% CI, -1.1, 8.5]) nor SpO2 (mean percentage differences from baseline after 48 microg formoterol, -0.37% [95% CI, -1.22, 0.47] and 800 microg salbutamol, -0.75% [95% CI, -1.73, 0.23]) changed significantly. However, SpO2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol. CONCLUSIONS In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.

Thunderstorm-related asthma: what happens and why

The fifth report issued by the Intergovernmental Panel on Climate Change forecasts that greenhouse gases will increase the global temperature as well as the frequency of extreme weather phenomena. An increasing body of evidence shows the occurrence of severe asthma epidemics during thunderstorms in the pollen season, in various geographical zones. The main hypotheses explaining association between thunderstorms and asthma claim that thunderstorms can concentrate pollen grains at ground level which may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20–30 min of a thunderstorm, patients suffering from pollen allergies may inhale a high concentration of the allergenic material that is dispersed into the atmosphere, which in turn can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm‐related events.

Climate Change and Air Pollution: Effects on Respiratory Allergy

A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by anthropogenic factors, have impact on the biosphere and human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between allergic respiratory diseases, asthma and environmental factors, such as meteorological variables, airborne allergens, and air pollution. Urbanization with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases and bronchial asthma observed over recent decades in most industrialized countries. However, it is not easy to evaluate the impact of climate changes and air pollution on the prevalence of asthma in the general population and on the timing of asthma exacerbations, although the global rise in asthma prevalence and severity could also be an effect of air pollution and climate change. Since airborne allergens and air pollutants are frequently increased contemporaneously in the atmosphere, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of respiratory allergy and asthma in atopic subjects in the last 5 decades. Pollen allergy is frequently used to study the relationship between air pollution and respiratory allergic diseases, such as rhinitis and bronchial asthma. Epidemiologic studies have demonstrated that urbanization, high levels of vehicle emissions, and westernized lifestyle are correlated with an increased frequency of respiratory allergy prevalently in people who live in urban areas in comparison with people living in rural areas. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc.) can affect both components (biological and chemical) of this interaction.

Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.

Since the discovery of immunoglobulin E (IgE) antibodies thirty-six years ago, our understanding of the mechanisms of allergy has improved to such an extent that we can now better differentiate allergy from non-allergic hypersensitivity, and allergic/atopic from intrinsic/non-atopic bronchial asthma. IgE antibodies are crucial immune mediators of airway inflammation in allergic atopic asthma and IgE-mediated hypersensitivity reactions are the likely mechanisms of allergen-induced airway obstruction. In addition, IgE may cause chronic airway inflammation in asthma through effector cells activated via high-affinity (Fcepsilon RI) or low-affinity (Fcepsilon RII) IgE receptors. Therapeutic anti-IgE antibodies able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (rhuMAb-E25; omalizumab) binds IgE at the same site as these antibodies bind Fcepsilon RI and Fcepsilon RII. As a consequence, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the Fcepsilon R1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma demonstrated that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted to be able to reduce asthma-related symptoms, to decrease corticosteroid use and to improve quality of life of asthmatic patients. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergies), a favourable side-effect profile and a twice-monthly dosing frequency.

Avoidance of allergens and air pollutants in respiratory allergy

Recent epidemiologic studies that used similar methodologies suggest that the prevalence of allergic airways diseases, particularly bronchial asthma, has increased over the last two decades (1±4). This trend involves many industrialized countries but also some developing ones where these disorders were unknown until recent years (5±9). It has been shown that the development of respiratory allergies depends on an interaction between genetic predisposition and environmental stimuli (allergens and adjuvant factors such as the components of urban air pollution) (10±14). Since we cannot assume a sudden variation of genetic background, it is likely that changes induced by human activities in indoor and outdoor environments, as well as a Westernized lifestyle, might play important roles in the increasing rate of atopic diseases in the general population (15±22). However, many other hypotheses have been proposed to explain these ®ndings (Table 1).

Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts: Two cases with two different patterns of onset

We describe two uncommon cases of oral allergy syndrome (OAS) after eating pistachio nuts (p.n.) in subjects (a 54‐year‐old man and a 3‐year‐old girl) with exclusive skin prick test (SPT) positivity to Parietaria (P.) and pistachio nut (p.n.) allergens. Serologic P.‐ and p.n.‐specific IgE determinations were also carried out. A double‐blind, placebo‐controlled food challenge (DBPCFC) was performed, for ethical reasons, only in the adult patient, but we observed a positive intraoral reaction only after slight scratching of the oral mucosa. Since this patient had put three whole p.n. with their shells into his mouth, breaking them with his teeth, before the onset of symptoms, we suggest that slight injury of the oral mucosa may enhance the local response. Preliminary results with SDS‐PAGE and immunoblotting demonstrate the occurrence of a slight degree of cross‐reactivity between these allergens, hut further studies are necessary to obtain a definite conclusion.

Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype

Background: Epidemiologic and clinical evidence supports the existence of an obesity‐related asthma phenotype. No distinct pathophysiologic elements or specific biomarkers have been identified thus far, but increased oxidative stress has been reported. Objective: We aimed at verifying whether metabolomics of exhaled breath condensate from obese asthmatic (OA) patients, lean asthmatic (LA) patients, and obese nonasthmatic (ONA) subjects could recognize specific and statistically validated biomarkers for a separate “asthma‐obesity” respiratory metabolic phenotype, here defined as “metabotype.” Methods: Twenty‐five OA patients, 30 ONA subjects, and 30 mild‐to‐moderate LA age‐matched patients participated in a cross‐sectional study. Nuclear magnetic resonance (NMR) profiles were analyzed by using partial least‐squares discriminant analysis, and the results were validated with an independent patient set. Results: From NMR profiles, we obtained strong regression models that distinguished OA patients from ONA subjects (quality parameters: goodness‐of‐fit parameter [R2] = 0.81 and goodness‐of‐prediction parameter [Q2] = 0.79), as well as OA patients from LA patients (R2 = 0.91 and Q2 = 0.89). The all‐classes comparison (R2 = 0.86 and Q2 = 0.83) indicated that OA patients possess a respiratory metabolic profile fully divergent from those obtained in the other patient groups. We also identified specific biomarkers for between‐class separation, which are independent from clinical bias. They are involved in the methane, pyruvate, and glyoxylate and dicarboxylate metabolic pathways. Conclusions: NMR‐based metabolomics indicates that OA patients are characterized by a respiratory metabolic fingerprint fully different from that of patients independently affected by asthma or obesity. Such a phenotypic difference strongly suggests unique pathophysiologic pathways involved in the pathogenesis of asthma in adult obese subjects. Furthermore, the OA metabotype could define a strategy for patient stratification based on unbiased biomarkers, with important diagnostic and therapeutic implications.