The allergens were gently pricked onto the skin surface of the vo

The allergens were gently pricked onto the skin surface of the volar side of the forearm. Wheal and flare reactions were read 20 min later (a test result was regarded as positive when a wheal of at least 3 mm in diameter appeared, with a surrounding flare, which was larger than the solvent, that is, negative control). The solvent alone (0.9 % sodium chloride) and histamine (0.01 mg/mL) were tested in parallel as negative and positive controls. SIC (specific inhalation challenge)

The SIC method performed in exposure chamber (0.5–5.5 ppb for 120 min) described elsewhere (Baur et al. 1994; Budnik et al. 2011). FEV1 was measured before and every 10 min for the 1st h, then hourly IWR-1 mw for 7 h. The SIC result was considered positive when the fall in FEV1 was at least 20 %. Clinical diagnosis of patients Cabozantinib manufacturer with MDI exposure history The individual asthma diagnosis for each patient followed the ERS/ATS guidelines (Anees et al. 2011; Moore et al. 2010; Vandenplas et al. 2011; Tarlo et al. 2008; Baur et al. 1998) as described in detail

below. See Table 1, for the schematic diagnostic criteria and supplementary Fig. 1 for diagnostic flow chart of the MDI-asthma diagnosis (see Figure 1 in supplementary material). Facultative diagnostic testing In case of uncertainness due to clear-cut work-related symptoms (e.g. associated with the absence of NSBHR), additional spirometry monitoring and/or additional specific inhalative challenge tests were performed (supplementary Fig. 1). Diagnosis of MDI hypersensitivity pneumonitis (MDI alveolitis) Diagnosis of MDI hypersensitivity pneumonitis has enough been described in detail elsewhere (Baur et al. 1992, 2001; Merget et al. 2002). Prerequisites of acute or subacute MDI hypersensitivity pneumonitis are the following: Occupational/environmental history:

MDI exposure. Respiratory as well as systemic symptoms after a lag period of 3–12 h: fever, shivering, malaise, cough and shortness of breath. Diagnostic scheme in case of presumed MDI hypersensitivity pneumonitis is shown in the Table 2. Exposure assessment Exposure assessment was performed using the MDA-SPM toxic gas monitor (Honeywell Analytics, Glinde, Germany) and was confirmed by biomonitoring (Budnik et al. 2011). If workplace measurement was not possible, the assessment of exposure was based on occupational case history, detailed reconstruction of the working conditions, data provided by industrial hygienists as well as information provided by the employees. Preparation of various MDI-HSA conjugates and immunological analysis The preparation of MDI-HSA conjugates in-vapor and in-solution is a modification of previously published methods (Wisnewski et al. 2004; Sepai et al. 1995; Kumar et al. 2009; Baur 1983).

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