Background: The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non‐lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer.Methods: Twenty‐six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment.Results: White blood cell count, platelet count, serum C‐reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin‐antithrombin complex, and D‐dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05).Conclusion: Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors.

Background The pathogenesis of aspirin‐induced asthma (AIA) is presumed to involve the aspirin/non‐steroidal anti‐inflammatory drug (NSAID)‐induced abnormal metabolism of arachidonic acid, resulting in an increase in 5‐lipoxygenase (5‐LO) metabolites, particularly leukotriene C₄ (LTC₄). However, the role of LTC₄ in the development of AIA has yet to be conclusively demonstrated. Objective The aim of this study was to evaluate the contribution of the lipid product LTC₄ secreted by the 5‐LO pathway to the pathogenesis of AIA. Methods To evaluate antigen‐induced airway inflammation, the concentrations of T‐helper type 2 cytokine in bronchoalveolar lavage fluid (BALF) obtained from LTC₄ synthase‐transgenic (Tg) and wild‐type (WT) mice after challenge with ovalbumin were measured. Subsequently, the ex vivo and in vivo effects of the NSAID sulpyrine were investigated in these Tg and WT mice by measuring the secretion of LTC₄ from sulpyrine‐treated BAL cells and the levels of LTC₄ in BALF following challenge with sulpyrine. Finally, the sulpyrine‐induced airway response by the administration of pranlukast, an antagonist of the cysteinyl (cs)‐LT1 receptor, was analysed. Results The concentrations of IL‐4, ‐5, and ‐13 in BALF from Tg mice were significantly higher than those in WT mice. In addition, sulpyrine augmented the secretion of LTC₄ in BALF and by BAL cells in Tg mice, but not in WT mice. Additionally, the increased airway resistance induced by sulpyrine could be reduced by treatment with pranlukast. Furthermore, the secretion of LTC₄ from mast cells, eosinophils, and macrophages was increased in the allergen‐stimulated LTC₄ synthase gene Tg mice, even in the absence of sulpyrine, as well as in BAL cells after sulpyrine. Conclusion and clinical relevance The over‐expression of the LTC₄ synthase in a mouse asthma model also replicates the key features of AIA. And our study supports that cys‐LTs play a major role in the pathogenesis of AIA in patients with chronic asthma. Cite this as: H. Hirata, M. Arima, Y. Fukushima, K. Honda, K. Sugiyama, T. Tokuhisa and T. Fukuda, Clinical & Experimental Allergy, 2011 (41) 1133–1142.

Purpose: The prognosis of rheumatoid arthritis (RA) with interstitial lung disease (ILD) is particularly poor. Although drugs that do not contribute to the progression of ILD should be used in RA treatment, none have been established. This study evaluated the safety of tocilizumab in terms of ILD activity. Patients and Methods: This study prospectively enrolled all 55 patients with RA complicated by ILD who were treated with tocilizumab at Dokkyo Medical University Saitama Medical Center from April 2014 to June 2022. The outcome measures were MMP-3 and KL-6 as biomarkers of RA and ILD activity, respectively, and the relationship between them was analyzed. Results: Both MMP-3 and KL-6 were significantly improved at 6 months of treatment (P < 0.001 and P < 0.05, respectively), and a weak correlation between MMP-3 and KL-6 was observed (R² = 0.086, P = 0.087). The group with increased MMP-3 due to RA progression had significantly higher KL-6 at 6 months compared with the group with RA improvement (P < 0.05). Also, the group with ILD progression on computed tomography had significantly higher MMP-3 compared with the groups with improvement or no change of ILD (P < 0.05 and P < 0.01, respectively). The mortality rate was 0% at 6 months, 2.0% at 1 year, 16.7% at 2 years, and 32.4% at 3 years, and mortality from acute exacerbation of ILD due to respiratory infection increased over time. Conclusion: RA activity and ILD activity were found to be related at 6 months of treatment. Tocilizumab does not seem to affect the mechanism of ILD progression, as most patients showed improvement in both MMP-3 and KL-6 with tocilizumab within 6 months, when this drug would be expected to affect the lungs directly. However, respiratory infection exacerbated ILD from 1 year after the start of treatment. As immunosuppressive drugs, including tocilizumab, have a risk of respiratory infection, it is important to identify early signs of infection.

Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P < 0.01) between hornet (R = 0.92) or paper wasp venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients. The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan.