Background Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been hampered by the lack of an animal model that mimics the human disease in a short time-frame. Objectives To create an early onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. To use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in COPD. Methods Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathological features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated using depletion and in vitro studies and MC protease-6 deficient mice. Results After just 8 weeks of smoke exposure, wild-type mice developed chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid-resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart, and increased susceptibility to respiratory infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced pro-inflammatory responses from cultured macrophages. Conclusion A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs.

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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on | 389 PAGANI et Al. 1 | INTRODUC TI ON Chemotherapeutic drugs have been used in the treatment of neoplasms since the 1940s. 1,2 Many types of antineoplastic agents were introduced in clinical practice and, despite the great diffusion of biological agents, chemotherapy (CHT) still represents the gold standard for the treatment of the majority of cancers, alone or in combination with the so-called more selective targeted therapies, namely monoclonal antibodies or other biologicals. 3 However, CHT can induce hypersensitivity reactions (HSRs) and remains the third leading cause of fatal drug-induced anaphylaxis in the United States. 4 Deaths related to CHT have also been reported in Europe. 5 This position paper aims to provide consensus on investigating HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections in this paper cover risk factors, pathogenesis, symptoms and signs of reactions, the role of skin tests, in vitro tests, indications and contraindications of drug provocations tests and desensitization of neoplastic patients with allergic reactions to CHT. Table 1 reports the main classes of CHT, their clinical indications, the characteristics of HSRs and their possible pathogenetic mechanisms. 2 | ME THODS This Position Paper was commissioned by the European Academy of Allergy and Clinical Immunology (EAACI). The task force group performed an intensive electronic literature search in MEDLINE, PubMed, databases of scientific societies, and reports of the AEMPS, European Medicines Agency, and the United States Food and Drug Administration by using the primary key words: hypersensitivity to chemotherapeutic drugs, hypersensitivity to antineoplastic agents, platinum compound hype...