Allergy, Asthma & Immunology Research最新文献

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Purpose: Humulus japonicus (HJ) is one of the most important causes of weed pollinosis in East Asia. The 10 kDa protein with pI 10 in 2-dimensional gel has been recognized as the representative major allergen of HJ, but its major allergens have not been characterized. This study aimed to characterize the major allergen of HJ.

Methods: A major allergen in Japanese hop was detected by proteome analysis; it was purified to homogeneity and its sequence was obtained by transcriptome analysis. The recombinant proteins were produced in Escherichia coli and Pichia expression systems, and their immunoglobulin E (IgE) reactivities were compared to those of the natural counterpart. We also analyzed post-translational modifications such as glycosylation and phosphorylation.

Results: Pectin methylesterase inhibitor, Hum j 6, was found to be the major allergen of HJ, and in silico signal peptide prediction corresponds to a 15.1 kDa protein with a theoretical pI of 8.28. Natural Hum j 6 was recognized by IgE antibodies from 86.4% (19/22) of HJ pollinosis patients, whereas the recombinant proteins did not show strong IgE reactivity. No glycosylation was detected, while at least 15 phosphorylated amino acids, possibly causing the pI and molecular weight shift, were detected by tandem mass spectrometry analysis.

Conclusions: Hum j 6 was identified as the representative major allergen of HJ and seems to be modified significantly after translation. These findings are useful for the development of component-resolved diagnosis and immunotherapy.

Purpose: Only limited studies have depicted the unique features and management of refractory chronic cough (RCC) and unexplained chronic cough (UCC). These led to the initiation of this study, which reported the demographic characteristics, manifestations, and long-term outcomes on a large series of consecutive RCC/UCC patients, providing a guideline-led real-world clinical experience.

Methods: Retrospective baseline information was obtained from Clinical Research Database (January 2016 to May 2021). At least 6 months after the last clinic visit, included subjects were prospectively followed up.

Results: Three hundred and sixty-nine RCC and UCC patients (199 females, 53.9%) were analyzed. The median cough duration was 24.0 (12.0-72.0) months. Laryngeal symptoms were reported in 95.9% of the patients. The common triggers for coughing were talking (74.9%), pungent odors (47.3%), eating (45.5%), and cold air (42.8%). RCC was considered in 38.2%, and the remainder of 228 patients had UCC, with an equal sex distribution (P = 0.66). Among the 141 RCCs, 90.8% (128) had refractory reflux cough, which was more responsive to current treatments (P < 0.01). Although most features and test results between RCC and UCC were similar, UCC was more commonly inappropriately treated (P < 0.01). Nineteen (7.7-41.1) months after the final clinic visit, 31.2% still coughed persistently, while 68.8% reported cough improvement or remission. RCC reported more favorable treatment outcomes (including cough improvement, control, and spontaneous remission) than UCC (P < 0.01). Coughs with long duration before the initial cough clinic visit (P < 0.01), frequent urinary incontinence (P < 0.01), and being sensitive to "talking" (P < 0.01) or "cold air" (P < 0.01) were less likely to be solved.

Conclusions: The current treatments only improve cough symptoms in two-thirds of patients. Clinical indicators for treatment failure were those coughing for long duration and being sensitive to "talking" or "cold air."

Primary immunodeficiency diseases (PIDs) are uncommon in adults; however, immunoglobulin G subclass deficiency (IGGSCD) is often found in a subset of adult patients with chronic respiratory diseases. As quantitative laboratory tests are used to diagnose IGGSCD, the clinical significance of IGGSCD remains controversial. However, respiratory infection is a common presenting feature of IGGSCD, and respiratory complications are responsible for subsequent morbidities, such as severe asthma, bronchiectasis, chronic obstructive airway diseases, and mortality. This review summarizes the current epidemiological data for PIDs, focusing on IGGSCD in the adult population. In addition, the investigation, treatment, and management strategies are detailed, including distinct issues faced by patients with chronic airway disease and their physicians in the proper diagnosis and treatment of IGGSCD.

Purpose: Several studies have reported a possible link between chronic rhinosinusitis (CRS) and rheumatoid arthritis (RA). However, it remains unclear whether CRS could influence the risk of developing RA. Therefore, in this study, we focused on examining the association between CRS and RA.

Methods: A total of 14,867 individuals with CRS and 14,867 without CRS were enrolled after 1:1 propensity score match from a nationwide longitudinal cohort database in South Korea. RA incidence was assessed using person-years at risk, and the hazard ratio (HR) was examined using the Cox proportional hazards model.

Results: The incidence of RA (per 1,000 person-years) was 6.51 for those with CRS, 6.55 for those with CRS without nasal polyps (CRSsNP), and 5.96 for those with CRS with nasal polyps (CRSwNP). We found that CRS individuals had a significantly increased risk of subsequent RA development with an adjusted HR of 1.41, regardless of the phenotype (adjusted HR was 1.42 in CRSsNP and 1.37 in CRSwNP patients). Moreover, the risk of developing RA over time was relatively higher within the first 4 years after the diagnosis of CRS.

Conclusions: Our nationwide population-based cohort study suggests that CRS may be associated with a subsequent increase in RA events, regardless of the phenotype. Therefore, physicians should consider RA risk when diagnosing and treating CRS patients.

Purpose: Although estrogen receptors (ERs) signal pathways are involved in the pathogenesis and development of asthma, their expressions and effects remain controversial. This study aimed to investigate the expressions of ERα and ERβ as well as their mechanisms in airway remodeling and mucus production in asthma.

Methods: The expressions of ERα and ERβ in the airway epithelial cells of bronchial biopsies and induced sputum cells were examined by immunohistochemistry. The associations of ERs expressions with airway inflammation and remodeling were evaluated in asthmatic patients. In vitro, the regulations of ERs expressions in human bronchial epithelial cell lines were examined using western blot analysis. The epidermal growth factor (EGF)-mediated ligand-independent activation of ERα and its effect on epithelial-mesenchymal transitions (EMTs) were investigated in asthmatic epithelial cells by western blot, immunofluorescent staining, and quantitative real-time polymerase chain reaction.

Results: ERα and ERβ were expressed on both bronchial epithelial cells and induced sputum cells, and the expressions showed no sex difference. Compared to controls, male asthmatic patients had higher levels of ERα on the bronchial epithelium, and there were cell-specific expressions of ERα and ERβ in induced sputum. The expression of ERα in the airway epithelium was inversely correlated to forced expiratory volume in 1 second (FEV1) % and FEV1/forced vital capacity. Severe asthmatic patients had significantly greater levels of ERα in the airway epithelium than mild-moderate patients. ERα level was positively correlated with the thickness of the subepithelial basement membrane and airway epithelium. In vitro, co-stimulation of interleukin (IL)-4 and EGF increased the expression of ERα and promoted its nuclear translocation. EGF activated the phosphorylation of ERα via extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways. ERα knockdown alleviated EGF-mediated EMTs and mucus production in airway epithelial cells of asthma.

Conclusions: ERα contributes to asthmatic airway remodeling and mucus production through the EGF-mediated ligand-independent pathway.

Dysregulation of the arachidonic acid metabolic pathway is the most widely known pathomechanism of aspirin-exacerbated respiratory disease (AERD). This study aimed to perform integrative analysis of transcriptomic and epigenomic profiling with network analysis to determine the novel pathogenic features of AERD. Ten patients with asthma including 5 patients with AERD and another 5 patients with aspirin tolerant asthma (ATA) were enrolled. Nasal scraping was performed and nasal mucosa was used in omics profiling. Peripheral eosinophil counts, sputum eosinophil counts, fractional exhaled nitric oxide levels, and pulmonary function test results were evaluated. Differentially expressed genes (DEGs), differentially methylated probes (DMPs) and differentially correlated genes (DCGs) between patients with AERD and those with ATA were analyzed. Network analysis using ingenuity pathway analysis (IPA) was performed to determine the gene connection network and signaling pathways. In total, 1,736 DEGs, 1,401 DMPs, and 19 pairs for DCGs were identified. Among DCGs, genes related to vesicle transport (e.g., RAB3B and STX2) and sphingolipid dysregulation (e.g., SMPD3) were found to be hypo-methylated and up-regulated in AERD. Using the canonical pathway analysis of IPA with 78 asthma-related DEGs, signaling pathways of T helper cell differentiation/activation and Fcε receptor I were generated. Up-regulation of RORγt and FcER1A were noted in AERD. Gene expression levels of RAB3B, SYNE1, STX2, SMPD3 and RORγt were significantly associated with sputum eosinophil counts. Quantitative real-time polymerase chain reaction was performed and mRNA expression levels of STX2, SMPD3, RORγt, and FcER1A were significantly higher in AERD compared to ATA. Distinct pathogenic features were identified by using integrative multi-omics data analysis in patients with AERD.