Comprehensive analysis of allergen-specific IgE in COPD: mite-specific IgE specifically related to the diagnosis of asthma-COPD overlap.

BACKGROUND: Although the relationship between allergic sensitization and increased respiratory symptoms of chronic obstructive pulmonary disease (COPD) has been suggested, which allergen has a significant effect on COPD pathology is unclear. This study aimed to identify the specific IgE related to clinical features of COPD and the diagnosis of asthma-COPD overlap (ACO). METHODS: We recruited 76 patients with COPD and analyzed 39 IgE using panel IgE test (View Allergy 39®). ACO was diagnosed according to the Japanese Respiratory Society Guidelines. RESULTS: As for perennial aeroallergens, the positivity for moth (31.5%), Candida (23.7%), Dermatophagoides pteronyssinus (22.4%) and house dust (22.4%), and concerning pollen, Japanese cedar (35.5%) and Japanese cypress (22.2%) exceeded 20%. Only the positivity of IgE for Dermatophagoides pteronyssinus and house dust was significantly higher in ACO compared with that in non-ACO COPD. Moreover, it contributed to the diagnosis of ACO in an IgE class-dependent manner. Patients with cockroach IgE exhibited higher residual volume, whereas those with Japanese cedar IgE exhibited better diffusion capacity than negative patients. The contribution for ACO diagnosis by the receiver operating characteristic curve analysis was comparable among total IgE (cutoff value: 158 IU/mL), blood eosinophil count (234/µL), and fraction of exhaled nitric oxide (31.0 ppb). CONCLUSIONS: The prominent role of mite-specific IgE in the diagnosis and pathology of ACO and the potentially detrimental effect of cockroach sensitization on air trapping in COPD were suggested. The finding highlights the future development of a treatment targeting IgE as a treatable trait in COPD.

[PREVALENCE OF FUNCTIONAL DYSPEPSIA SYMPTOMS IN PATIENTS WITH ASTHMA].

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common comorbidity among patients with asthma. In addition, functional dyspepsia (FD) is characterized by upper abdominal symptoms without organic disease manifestations. However, the prevalence of FD among patients with asthma remains uninvestigated; therefore, herein, we investigated the prevalence of dyspepsia symptoms in these patients. METHODS: We recruited 156 patients with asthma from the outpatient clinic of Teikyo University Hospital and investigated the prevalence of dyspepsia symptoms using the modified Frequency Scale for the Symptoms of GERD. Further, the relationship between dyspepsia symptoms and clinical background of asthma was also investigated. RESULTS: Certain digestive organ symptoms were exhibited by 83% of patients with asthma, dyspepsia symptoms by 44%, and reflux symptoms by 26%. The dyspepsia-dominant group showed significantly higher female ratio and numerically lower %FEV1 than the asymptomatic group. In the group with dyspepsia score >5 points, the ratio of patients undergoing step 4 asthma treatment and the ratio of those using long-acting muscarinic receptor antagonist were higher than those in the group with a score <5 points. Furthermore, endoscopic diagnosis was also made in 84 patients and the prevalence of FD was 21%. CONCLUSION: A considerable proportion of patients with asthma exhibited dyspepsia symptoms, and the asthma severity in patients with dyspepsia was higher than those in asymptomatic patients. Based on the current findings, more attention should be directed to FD, in addition to GERD, as a comorbidity of the digestive system in patients with asthma.

IL-9 Blockade Suppresses Silica-induced Lung Inflammation and Fibrosis in Mice.

Recapitulative animal models of idiopathic pulmonary fibrosis (IPF) and related diseases are lacking, which inhibits our ability to fully clarify the pathogenesis of these diseases. Although lung fibrosis in mouse models is often induced by bleomycin, silica-induced lung fibrosis is more sustainable and more progressive. Therefore, in this study, we sought to elucidate the mediator(s) responsible for the pathogenesis of lung fibrosis, through the use of a mouse model of silica-induced lung fibrosis. With a single nasal administration of 16 mg of silica, lung inflammation (assessed by elevated cellular components in the BAL fluids [BALFs]) and lung fibrosis (assessed by lung histology and lung hydroxyproline levels) were induced and sustained for as long as 24 weeks. Of the mediators measured in the BALFs, IL-9 was characteristically elevated gradually, and peaked at 24 weeks after silica administration. Treatment of silica-challenged mice with anti-IL-9-neutralizing antibody inhibited lung fibrosis, as assessed by lung hydroxyproline level, and suppressed the levels of major mediators, including IL-1ß, IL-6, IL-12, CCL2, CXCL1, and TNF-α in BALFs. Moreover, human lung specimens from patients with IPF have shown high expression of IL-9 in alveolar macrophages, CD4-positive cells, and receptors for IL-9 in airway epithelial cells. Collectively, these data suggest that IL-9 plays an important role in the pathogenesis of lung fibrosis in diseases such as IPF.

Leukotriene receptor antagonist attenuated airway inflammation and hyperresponsiveness in a double-stranded RNA-induced asthma exacerbation model.

BACKGROUND: Viral infections are the most common triggers of asthma exacerbation, but the key molecules involved in this process have not been fully identified. Although cysteinyl leukotrienes (cysLTs) have been postulated as the key mediators, their precise roles remain largely unclear. To investigate the roles of cysLTs in virus-induced asthma exacerbation, we developed a murine model using a viral double-stranded RNA analog, polyinosinic-polycytidylic acid (poly I:C), and analyzed the effect of leukotriene receptor antagonist (LTRA) administration. METHODS: A/J mice were immunized with ovalbumin (OVA) + alum (days 0, 28, 42, and 49), followed by intranasal challenge with OVA (phase 1: days 50-52) and poly I:C (phase 2: days 53-55). Montelukast was administered during poly I:C challenge (phase 2) in the reliever model or throughout the OVA and poly I:C challenges (phases 1 and 2) in the controller model. Airway responsiveness to acetylcholine chloride was assessed, and bronchoalveolar lavage (BAL) was performed on day 56. RESULTS: Administration of poly I:C to OVA-sensitized and -challenged mice increased the number of eosinophils and levels of IL-13, IL-9, CCL3, and CXCL1 in BAL fluid (BALF) and tended to increase airway responsiveness. Montelukast significantly attenuated the poly I:C-induced increase in the number of eosinophils and levels of IL-13, IL-9, and CCL3 in BALF and airway hyperresponsiveness in both the reliever and controller models. CONCLUSIONS: This is the first report showing that LTRA functionally suppressed the pathophysiology of a virus-induced asthma exacerbation model, suggesting the importance of cysLTs as a potential treatment target.

Toll-like receptor 3 ligand specifically induced bronchial epithelial cell death in caspase dependent manner and functionally upregulated Fas expression.

BACKGROUND: Viral infections are the most common cause of asthma exacerbation. Virally infected epithelial cells undergo apoptosis. Although in healthy conditions, apoptosis may have a host-defensive role in limiting virus spread, this process may have a detrimental effect on damaged epithelium in asthma. Toll-like receptors (TLRs) are the receptors for various pathogens, and viruses possess several components that can activate TLR3, TLR4, and TLR7/8. However, as it has not been determined as to which component is responsible for virus-induced epithelial cell apoptosis, we comprehensively analyzed the effects of all TLR ligands on apoptosis. METHODS: BEAS-2B cells or primary cultured human bronchial epithelial cells (PBECs) were stimulated by TLR 2, 3, 4, 5, 7/8, and 9 ligands and cell death was analyzed by flow cytometry. Chemokine generations induced by these ligands were also analyzed. RESULTS: The TLR3 ligand polyinosinic-polycytidylic acid (poly I:C) specifically induced chemokine generation and apoptosis, while other TLR ligands including those for TLR5, 7/8, and 9 had no effect. The response to poly I:C had two phases, which included rapid secretion of chemokines and subsequent apoptosis in a later phase. Poly I:C induced apoptosis in a caspase-dependent manner and functionally upregulated the expression of Fas. CONCLUSIONS: Previous findings indicating that viruses induced caspase-dependent death and upregulated Fas expression were reproduced by poly I:C, suggesting the central role of dsRNA/TLR3 in virus-induced apoptosis. Since these processes may have detrimental effects on pre-existing epithelial damage, the dsRNA/TLR3 pathway may be potential novel treatment target for virus-induced exacerbation of asthma.

[Case report: anaphylaxis caused by linseed included in baked bread].

We recently experienced a 29-year-old female with anaphylaxis caused by linseed included in homemade bread. This is the first report of linseed-induced allergy in Japan. She obtained the linseed-containing ingredients of bread by mail order. We performed skin-prick tests and basophil degranulation tests using extracts of the ingredients and commercially available linseeds; both tests showed positive results for linseed. The patient's serum was also positive for linseed-specific IgE. Since linseeds are included in various kinds of foods and exposure to them is increasing, linseeds may need to be recognized as a potential trigger of immediate-type allergy in Japan.