Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA2LEN and InterAirways document

Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research.     

Asthma treatment: 'magic bullets which seek their own targets'

The most fascinating options of the new asthma treatments are probably represented by monoclonal antibodies. In fact, these molecules are virtually able to interact with whatever specific antigen. Anyway, it is mandatory to understand the limits of this group of molecules, in terms of both efficacy and safety. In this review, we have analyzed different ways of interfering along the course of the cascade of the allergic reaction, targeting different molecules (CD4, TNF-α, IL-4, IL-5, IL-10, IL-12, endothelial adhesion molecules, IgE), showing the efficacy and the risks of each kind of treatment. In the end, we focused our attention on omalizumab, the monoclonal antibody targeting IgE. Although with some restrictions, represented by the high costs and the limitation of its use only to a specific subset of patients affected by allergic asthma, at present anti-IgE appear to be the only 'magic bullet' for the treatment of allergic asthma. In fact, it proved to reduce exacerbations and symptom scores, and to improve quality of life, with a very good safety profile.     

Aerobiological diagnosis of respiratory allergy by a personal sampler: two case reports.

We describe two cases of respiratory allergy (asthma), which were difficult to diagnosis from an etiological viewpoint. The routine diagnostic tests were not able to determine the causal allergens, although the clinical history suggested that allergens were confined to restricted environments. Therefore, an aerobiological sampling by means of a battery-powered portable device was carried out. This approach allowed identification of the responsible allergens, which were Alternaria spores in one case and thuja pollen in the other. Once a targeted environmental care had been performed, the patients' symptoms rapidly improved and antiasthma therapy could be stepped down or discontinued. We suggest that, in selected cases of difficult diagnosis the presence of proximity allergens is suspected, aerobiological sampling with a portable device should be considered.     

Phenotypic and functional analysis at the clonal level of infiltrating T lymphocytes in papillary carcinoma of the thyroid: prevalence of cytolytic T cells with natural killer-like or lymphokine-activated killer activity

We investigated the phenotype and function of thyroid tumor-, metastatic lymph node-, and peripheral blood-derived T lymphocytes of four patients with papillary thyroid cancer. Both phenotypic analysis of freshly isolated cells and clonal analysis, using a high efficiency cloning technique, were performed. For comparison, intrathyroid and peripheral blood T lymphocytes derived from patients with autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis) have been studied. In papillary cancer, the phenotype of thyroid and lymph node-derived T lymphocytes did not differ from that of peripheral blood lymphocytes of the same patients or lymphocytes from normal peripheral blood. At variance with respect to autoimmune thyroid disease, activation markers were poorly represented. The functional analysis of T cell clones showed similar proportions of interleukin-2-producing (helper-inducer) clones in thyroid, lymph node, and peripheral blood, slightly lower than in Hashimoto's thyroiditis and slightly higher than in Graves' disease. With regard to effector function, we found lower proportion of clones with cytolytic activity in a lectin-dependent assay compared to that in Hashimoto's thyroiditis. Interestingly, however, the proportions of cytolytic clones displaying cytolytic activity against the neoplastic cell line K562 (natural killer-like activity) or fresh unrelated tumor cells (lymphokine-activated killer activity) were relatively high in thyroid cancer infiltrates.     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Genuair® Usability Test: Results of a National Public Survey of the Elderly

Proper use of inhaler devices may be problematic in elderly patients due to age-related difficulties. A survey was administered to elderly patients to investigate the usability of the Genuair® device and patients' subjective viewpoint on the device. A representative sample of the Italian population aged ≥ 65 years was completed with a pre-defined sample of 89 patients with hand arthritis/arthrosis. Of 526 respondents, 88 were not self-sufficient. Only the replies of the 438 self-sufficient respondents were analyzed. A total of 107 participants (24%) reported having respiratory diseases, and 81 of these (76%) were users of inhaler devices. After the first test, the device was considered “practical/handy” by 90% of patients and “easy to use” by 89%. After the second test, in which patients received a demonstration of the correct inhalation maneuver, the percentage of patients scoring ≥ 7 increased to 93% for the first characteristic and was confirmed for the second, with no differences between the groups in terms of age, educational level, use of devices, and presence of arthritis/arthrosis. The mean time to explain the inhaler technique and to perform a correct inhalation was 1'38"± 1'37", and 70% of the respondents required less than 2 minutes, with no differences between the groups in terms of age, education level, use of devices, and presence of arthritis/arthrosis. In conclusion, Genuair® was well accepted and easy to use in a representative sample of the Italian population aged ≥ 65 years. These characteristics make it a valid choice in the elderly, thus enabling patients to better cope with the problems and difficulties that are common to this age group.     

Topical acetylsalicylic acid in the treatment of allergic pollinosic conjunctivitis.

The pharmacological treatment of allergic conjunctivitis includes the use of topical antiinflammatory drugs, i.e. steroids and NSAIDs (nonsteroidal antiinflammatory drugs), such as acetylsalicylic acid (ASA). However, steroids are not suitable in prolonged treatment, as well as in pollinosis in the Mediterranean area, because of their side effects. The present double-blind study evaluates the topical use of acetylsalicylic acid eye drops (1% solution) compared to placebo in the treatment of patients with seasonal allergic conjunctivitis during the period June-July 1990. The patients were randomized and treated with ASA eye drops or placebo eye drops, both applied as one drop in each eye q.i.d. for 14 days. The severity of symptoms was evaluated before and after treatment by the investigator and the patient. An overall judgement of therapeutic response was expressed independently by the patient and the investigator at the end of the treatment. The ASA-treated group improved significantly compared to the placebo-treated group. No serious side effects were observed. The results confirm the clinical efficacy and safety of topical ASA in the treatment of pollen-induced allergic conjunctivitis.