The potential role of local pharmacies to assess asthma control: an Italian cross-sectional study.

BACKGROUND: Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay between secondary and primary care services as an effective strategy to control the disease, community pharmacies' are seldom involved in asthma control assessment. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies within the health district of the city of Verona (Veneto Region, North-Eastern Italy). METHODS: A call for participation was launched through the Pharmacists' Association of Verona. Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI). RESULTS: Fifty-seven community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. Most patients (92%) self-reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR = 0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT< 16 compared to those not taking medications regularly. CONCLUSIONS: Overall, our findings highlighted an unsatisfactory asthma control in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.

Subcutaneous allergen specific immunotherapy: best clinical practice as cornerstone for future development.

Allergen subcutaneous immunotherapy is a long lasting treatment which can modify the natural history of allergic respiratory diseases. Recommended administration is required for a minimum of three years. During this long term therapy the daily management is based on two crucial points, discussed in this review, such as the prevention and the treatment of side effects and the improvement and follow-up of patient adherence. This review specifically focuses on subcutaneous immunotherapy.

Long-term tolerability of etoricoxib in different types of NSAID-intolerant subjects.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of hypersensitivity reactions, therefore, in clinical practice, it's important to find safe and effective substances. OBJECTIVE: To evaluate the tolerability of etoricoxib and its subsequent actual use and safety at home. METHODS: Etoricoxib tolerance was assessed by single-blind-placebo-controlled oral challenges and its subsequent use was checked by a standardized telephone call. The test was performed in 139 subjects (83 single NSAID reactors and 56 multiple NSAID reactors). RESULTS: The drug was not tolerated in 4 cases (2.8%) causing wheals on the face area in 3 single reactors and a severe generalised reaction occurring three hours after the intake of a therapeutic dose in a multiple reactor. The phone calls showed that 64 (52.8%) patients did not take etoricoxib, mostly due to the fear of adverse effects; in 5 cases (4.2%), the practitioner prescribed a different NSAIDs. Only 52 (43%) subjects took etoricoxib after oral challenges; all tolerated the drug but 2 single reactors, who reported a very mild labial oedema. CONCLUSION: Our study confirmed the good long-term tolerability of etoricoxib in patients with a history of hypersensitivity to other NSAIDs without differences between single and multiple reactors. Nonetheless, in NSAID-intolerant subjects this drug should be first challenged in specialised centres due to the risk ofsevere reactions.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

Allergic rhinitis: pharmacotherapy in pregnancy and old age.

INTRODUCTION: Allergic rhinitis (AR) affects 20-30% of women in reproductive age and may worsen during pregnancy. About 10% of the elderly suffer from AR, and it could be under-diagnosed in these patients. Many drugs are currently available, however AR treatment during pregnancy and old age represents a challenging issue. AREAS COVERED: A review of the literature on the topic has been performed. Expert commentary: In pregnancy, drug avoidance should be carefully balanced with the need for AR optimal control. Topical drugs are suggested as a first approach. The safety and tolerability profile of second-generation antihistamines is well supported. If allergen immunotherapy (AIT) is ongoing and well tolerated, there is no reason for stopping it. AIT initiation in pregnancy is not recommended. For elderly patients, no specific concerns have been highlighted regarding topical treatments, except from nasal decongestionants. Second generation antihistamines are generally well tolerated. Old age should not preclude AIT.

Nimesulide in the treatment of patients intolerant of aspirin and other NSAIDs.

Aspirin (acetylsalicylic acid) and other NSAIDs are responsible for many adverse effects. Among them, pseudo-allergic reactions (urticaria/angioedema, asthma, anaphylaxis) affect up to 9% of the population and up to 30% of asthmatic patients. The mechanisms provoking these reactions have not been fully elucidated, but it appears that inhibition of cyclo-oxygenase (COX) plays a central role. The anti-inflammatory action of nimesulide differs from that of other NSAIDs, possibly because of its chemical structure. In particular, nimesulide is selective for COX-2 and displays additional properties in terms of its effects on inflammatory mediator synthesis and release. For these reasons, nimesulide is generally well tolerated by NSAID-intolerant patients and patients with NSAID-induced asthma. The good tolerability of nimesulide as an alternative drug for use in patients with NSAID intolerance has been demonstrated in a large number of clinical studies.

Anaphylaxis to pine nuts and immunological cross-reactivity with pine pollen proteins.

Despite the wide use of pine nuts, the fruit of Pinus pinea, only a few reports of allergic reactions to them have been published. We present herein a case of food allergy to pine nuts in a patient who showed no clinical symptoms to pine pollen despite the presence in her serum of specific IgE antibodies. In order to verify whether the reaction against pine nuts was IgE mediated, specific IgE against pine nuts and pollen were evaluated by skin-prick test, prick by prick and RAST. Immunoblotting and immunoblotting-inhibition were used to evaluate the allergenic components of both extracts and their cross-reactivity. Prick by prick with fresh pine nuts and RAST with pine nut and pine pollen extracts showed that the patient had high levels of specific IgE against both extracts. Immunoblotting experiments showed the presence in serum of IgE antibodies against several components in pine nuts and pollen. Immunoblotting-inhibition experiments demonstrated the presence of some cross-reacting components. These data confirm the existence of food allergy induced by pine nuts. This sensitization to pine nuts developed with no symptoms of pine pollinosis. Development of pollinosis may require a longer time of exposure to allergens. Based on the cross-reactivity between pine nut and pine pollen extracts, cosensitization to these two allergens could be possible.

Beer-induced anaphylaxis due to barley sensitization: two case reports.

Despite the large worldwide beer consumption, allergic reactions have very rarely been reported. We describe two cases of severe systemic reactions due to beer ingestion: one case of anaphylaxis requiring emergency care and one of generalized urticaria and angioedema. The two patients underwent a detailed diagnostic procedure involving skin testing, oral challenge with additives, detection of specific IgE to the components of beer, and oral challenge with beer in one patient. The results of the tests, in the particular skin tests and IgE assay, allowed us to detect barley as the specific ingredient responsible for the observed allergic reactions to beer. Therefore, such a sensitization should always be taken into account in the case of suspected reactions following beer ingestion.

Severe systemic reactions caused by poppy seed.

We describe a case of severe systemic reactions caused from poppy seed ingestion. Poppy seeds were suspected to be responsible for the symptoms on the basis of the clinical history. This suspicion was confirmed by skin testing and the prick-prick test. Moreover, a RAST assay was conducted with an extract of fresh food, confirming the presence of specific IgE to poppy seed. Although poppy seeds are not commonly used, we highlight the possible importance of such rare and often hidden sources of allergens.

The relationship between clinical efficacy of specific immunotherapy and serum intercellular adhesion molecule-1 levels.

The intracellular adhesion molecule-1 (ICAM-1) is a reliable marker of allergic inflammation; its soluble isoform in serum is hypothesized to reflect the severity of the disease, therefore it may be used to monitor the efficacy of specific immunotherapy. We evaluated the levels of soluble ICAM-1 in the serum of 14 patients with grass-induced respiratory allergy before and after 12 months of specific immunotherapy, and correlated this parameter with the clinical outcome, measured using a visual analog scale. We found that in the majority of the patients, soluble ICAM-1 levels paralleled the clinical trend of the disease, with a significant decrease of soluble ICAM-1 in patients with successful specific immunotherapy (Spearman's correlation test: r = 0.57; p < 0.001). Therefore, we hypothesize that soluble ICAM-1 could be regarded as a reliable indirect marker of specific immunotherapy efficacy and that it could be used for monitoring clinical outcome.

Evaluation of the nocebo effect during oral challenge in patients with adverse drug reactions.

The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance. The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure. We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions. Six hundred patients, seen in three different centres (Genoa, Naples and Verona) with a history of reactions to drugs, underwent a blind oral challenge with the administration of an indifferent substance and active drugs. The administration of an inert substance provoked untoward reactions in 54 patients (27%) in Verona, 60 (30%) in Naples and 48 (24%) in Genoa. The overall occurrence of nocebo effect was 27%. The majority of reactions were subjective symptoms (itching, malaise, headache etc), perceived as troublesome by all subjects. The occurrence was significantly higher in women than in men. Our data, collected in a large population, confirm that the nocebo effect occurs frequently in clinical practice. In managing adverse drug reactions through oral challenge the nocebo effect is mandatory to recognize false positive responses.

Tolerability of three selective cyclo-oxygenase-2 inhibitors, meloxicam, celecoxib and rofecoxib in NSAID-sensitive patients.

BACKGROUND: Patients with aspirin-sensitive respiratory and cutaneous diseases experience cross reactions to all nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclo-oxigenase (COX) enzymes. As are now available drugs which selectively inhibit COX-2, questions are raised whether cross-reactivity occurs between aspirin and these COX 2 inhibitors. OBJECTIVE: The aim of this study was to evaluate the tolerability of three COX-2 inhibitors (meloxicam, celecoxib and rofecoxib) in subjects with previous pseudoallergic respiratory and cutaneous reactions to NSAIDs. METHODS: 76 subjects with documented previous cutaneous and respiratory pseudoallergic reactions to aspirin and/or other NSAIDs underwent a single blind challenge with celecoxib, meloxicam and rofecoxib. RESULTS: All subjects with previous respiratory reactions tolerated all drugs. Three subjects with multiple-drug induced urticaria complained of a generalized reaction after challenge (Two due to celecoxib and one due to meloxicam). Among the group of patients with NSAIDs-induced urticaria five complained of a relapse of the disease due to rofecoxib (one subject), celecoxib (two subjects and meloxicam (two subjects). CONCLUSIONS: According to these results the cross-reactivity between aspirin and these COX-2 inhibitors does not occur in subjects with previous respiratory pseudoallergic reactions. A good safety profile was also demonstrated in patients with cutaneous reactions, being few reactions observed. However for this reason a controlled oral challenge with these drugs is useful for the proper management of patients sensitive to classic NSAIDs.

[Occupational asthma induced by casein inhalation]. / Asma professionale da inalazione di caseina.

Reported cases of occupational asthma due to inhalation of milk proteins are rare. Our report is about the first evidence of occupational asthma in a health care worker, caused by an hidden exposure to casein, contained in a commercial dermatological powder widely used in geriatric patients treatment. The diagnosis is based on the case-history and on the positive skin prick test to a commercial and extemporary extract of the occupational allergen.

[Epidemiology of allergic respiratory diseases: many questions, few answers]. / L'epidemiologia delle allergopatie respiratorie: molte domande, poche risposte.

Over the last twenty years an increase of allergic respiratory diseases has been observed, even if a broad variability of incidence has been reported. Asthma and allergic rhinitis are more common among young subjects, but there are data of an increase of allergic respiratory diseases in older patients. Moreover it has to be underlined the increase of the severity of these diseases, as shown by the higher use of anti-allergic drugs and by the increase of fatal asthma. The reasons of this trend are not understood. One reason can be the more appropriate diagnosis of asthma by the general practitioners. Other factors must be considered: the most important one can be air pollution; many air components (i.e. SO2, NO2, O3), particularly in industrialized countries, may play a role in allergic sensitization through an irritative-inflammatory mechanism. Socio-economic factors can also influence the incidence of allergic diseases. Other factors as cigarette smoke, foods, allergenic load have to be mentioned. Finally a viral etiology has been reported. Very recently, the allergic inflammation has been considered as the crucial event in the pathogenesis of allergic respiratory diseases. As allergic diseases can lead to chronic inflammation, an early and long-lasting treatment is mandatory.

[New drugs in the treatment of respiratory allergic diseases]. / Nuovi farmaci nella terapia delle allergopatie respiratorie.

The drugs recently available for the treatment of allergic respiratory diseases include: 1) topical steroids as fluticasone and budesonide; 2) nasal and ocular sodium nedocromil; 3) nasal N-acetyl-aspartyl-glutamic acid; 4) topical antihistamines as levocabastine and azelastine; 5) antileukotrienes and anti PAF (experimental). Topical steroids are the most effective drugs; the new molecules have a low gastric absorption and a rapid liver-metabolism which decreases the risks of systemic side effects. In the treatment of allergic conjunctivitis ocular sodium nedocromil seems to be more effective than cromoglycate, however further studies are needed to evaluate the effectiveness of the nedocromil nasal formulation. In allergic rhinitis good clinical results are obtained using NAAGA. In the treatment of allergic rhino-conjunctivitis topical antihistamines seem as effective as the antihistamines administered by oral route; moreover they cause less side effects. The anti-leukotrienes drugs can be used in the treatment of moderate asthma. In the treatment of bronchial asthma no clinical and functional improvement has been reported using PAF or thromboxane A2 receptor antagonists.

Evaluation of the IgE cross-reactions among vespid venoms. A possible approach for the choice of immunotherapy.

BACKGROUND: Hymenoptera venom allergy can be effectively cured with specific immunotherapy, thus the correct identification of the allergen is essential. In the case of multiple skin and serum positivities it is important to know if a cross-reaction among venoms is present. We studied by CAP-inhibition assays the degree of cross-reactivity between Vespula vulgaris and Polistes dominulus. METHODS: Serum samples were obtained from consecutive patients with a clinical history of grade III-IV reactions to hymenoptera sting and with nondiscriminative skin/CAP positivity to both Vespula and Polistes. Inhibition assays were carried out with a CAP method, incubating the sera separately with both venoms and subsequently measuring the specific immunoglobulin E (IgE) to venoms themselves. RESULTS: Forty-five patients (33 male, mean age 40 years, age range 12-74, total serum IgE 242 +/- 168 kU/l) were included. Their specific IgE to Vespula and Polistes were 12.03 +/- 5.70 kU/l and 10.7 +/- 2.0 kU/l (P = NS), respectively. At the CAP-inhibition assays, in 25 patients a >75% heterologous inhibition by P. dominulus venom against V. vulgaris-specific IgE was found. In six subjects V. vulgaris venom effectively inhibited the P. dominulus-specific IgE. In the remaining 14 cases the CAP-inhibition test provided intermediate and not discriminative results. CONCLUSION: In 31/45 patients, the double sensitizations to venoms were probably the result of cross-reactions and the CAP-inhibition allowed identifying the true double sensitizations. This approach may be helpful for the correct prescription of immunotherapy in the case of V. vulgaris and P. dominulus double positivity.

Clinical efficacy and safety of local nasal immunotherapy.

Local nasal immunotherapy represents an alternative route of allergen administration. It was proposed to overcome the risk of systemic reactions rarely reported during the traditional subcutaneous immunotherapy. Some studies carried out in the past generally showed good efficacy but poor tolerability. The aqueous extracts mostly used in these studies carry some drawbacks such as the volume effect, self-digestion and the difficulty of administering reproducible dosages. The recent availability of allergen extracts in powder form has led to better stability and standardization. The studies carried out with these freeze-dried allergens showed clinical efficacy and good tolerability in perennial (mite, cat) and seasonal (grass, birch, Parietaria) allergic rhinitis. According to these findings this new local nasal immunotherapy with extract in powder form represents a suitable alternative to the traditional immunotherapy in the treatment of allergic rhinitis.