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Background: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS., Methods: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV 1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA., Results: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV 1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV 1 , %MMEF, %PEF, and all IOS parameters., Conclusion: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases., (© 2024. The Author(s).)

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4 + cTfh cells were significantly decreased and the percentage of IFN-γ + cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Shigehara, Kamekura, Ikegami, Sakamoto, Yanagi, Kamiya, Kodama, Asai, Miyajima, Nishikiori, Uno, Yamamoto, Takano, Chiba, Ohnishi and Ichimiya.)

C-X-C motif chemokine ligand 9 (CXCL9), a candidate biomarker, reflects type 1 (T1) inflammation pathology. Here, we report the analytical performance and clinical characteristics of a new CXCL9 reagent for a fully automated immunoassay device. We evaluated the limits of blank, detection, and quantitation (LoQ) along with other efficacy parameters, and the ability of the assay to report patient health, COVID-19 status, and the presence of asthma and/or interstitial lung diseases (ILDs). The coefficient of variation for 5-day total precision using two instruments was 7% across two controls, serum, and plasma panels. LoQ of 2.2 pg/mL suggested the efficacy of the assay in detecting T1 inflammation in plasma or serum; no cross-reactivity or interference was observed. We identified high serum CXCL9 levels in samples from patients with acute COVID-19 infections (n = 57), chronic bird-related hypersensitivity pneumonitis (n = 61), asthma (n = 194), and ILDs (n = 84) compared to healthy individuals (< 39.0 pg/mL). Furthermore, CXCL9 levels increased with age in asthma patients, and an opposite trend was observed for T2 inflammatory factors. These results suggest the utility of the automated CXCL9 immunoassay for measuring CXCL9 in clinical samples and reflect its role in T1 inflammation., (© 2023. The Author(s).)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The decline in forced expiratory volume in one second (FEV 1 ) is considered to be one of the most important outcome measures for evaluating disease progression. However, the only intervention proven to improve COPD prognosis is smoking cessation. This study therefore investigated the factors associated with annual FEV 1 decline in COPD., Methods: This retrospective study followed up 65 patients treated for COPD for 5 years: 13 current smokers and 52 former smokers, 25 with pneumonia, 24 with asthma, 18 with cancer, and 17 with cardiovascular disease. The patients were divided into groups based on clinical cutoff parameters of the impulse oscillometry system (IOS): 11 high and 54 low R5, 8 high and 57 low R20, 21 high and 44 low R5-R20, 26 high and 39 low X5, 38 high and 27 low Fres, and 36 high and 29 low AX. We investigated whether the decline in FEV 1 was associated with comorbidities and IOS parameters., Results: The annual change in FEV 1 over 5 years was significantly affected by smoking status (current - 66.2 mL/year vs. former - 5.7 mL/year, p < 0.01), pneumonia (with - 31.5 mL/year vs. without - 8.9 mL/year, p < 0.05), asthma (with - 30.2 mL/year vs. - 10.8 mL/year, p < 0.01), but not by cancer and cardiovascular disease. In the groups defined by IOS results, only the high AX group had significantly more annual decline in FEV 1 and %FEV 1 than the low AX group (- 22.1 vs. - 12.8, p < 0.05 and - 0.20 vs. 0.40, p < 0.05, respectively)., Conclusions: Continuing smoking as well as complications in pneumonia and asthma would be risk factors for the progression of COPD. AX might be a suitable parameter to predict the prognosis of patients with COPD., (© 2022. The Author(s).)

Background: Bronchial asthma (BA) has different phenotypes, and it requires a clinically effective subtype classification system. The impulse oscillometry system (IOS) is an emerging technique device used in respiratory functional tests. However, its efficacy has not been validated. Therefore, this study aimed to assess the relationship between BA and the IOS parameters, and the difference in the therapeutic effects of inhaled corticosteroids (ICSs) among the subtype classifications was evaluated using the IOS., Methods: Of the 245 patients with bronchial asthma who were screened, 108 were enrolled in this study. These patients were divided based on three subtypes according to the IOS result as follows: central predominant type (n = 34), peripheral predominant type (n = 58), and resistless type (n = 16). Then, the following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). The treatment effects were assessed using the Asthma Health Questionnaire (AHQ) and the Asthma Control Test (ACT) and were compared among the three subtypes., Results: In the central predominant type, the AHQ score of the MF group was significantly higher than that of the FP group (15.4 vs. 3.6, p < 0.01) and the BUD group (15.4 vs. 8.8, p < 0.05); the ACT score of the FP group was significantly higher than that of the MF and BUD groups (24.3 vs. 21.7, 22.3, respectively, p < 0.05) at 4 weeks after treatment. In the peripheral predominant type, the AHQ score of the FP group was significantly higher than that of the MF group (14.1 vs. 3.4, p < 0.05); the ACT score of the FP group was lower than that of the MF and BUD groups (22.8 vs. 24.6, 24.4, respectively, p < 0.01) at 4 weeks after treatment., Conclusions: An association was observed between IOS subtype classification and ICS particle size in terms of therapeutic efficacy in BA. This result indicates that the IOS could be an effective tool in the selection of ICS and the evaluation of the BA phenotype.

Background: Biologics dramatically improve symptoms of severe asthma; however, various exacerbating factors may induce flare-up. Pneumocystis spp. have not been reported as a cause of asthma exacerbation during biologic use, although patients with severe asthma have high levels of antibodies against Pneumocystis spp. Case presentation: An 87-year-old female with severe asthma that was well-controlled with mepolizumab, who developed a steroid-resistant refractory flare-up. Chest computed tomography showed bilateral ground glass opacities, and results of polymerase chain reaction tests on induced sputum were positive for Pneumocystis DNA. Therefore, a diagnosis of Pneumocystis pneumonia was made. The clinical symptoms improved after treatment with sulfamethoxazole–trimethoprim. Conclusion: Clinicians should be aware of Pneumocystis pneumonia as a cause of refractory exacerbation of bronchial asthma during use of interleukin-5 inhibitors. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have been used for various carcinomas. However, immune‐related adverse events have been observed. There have been few reports of treatment with biologics for severe bronchial asthma induced by ICI; therefore, their efficacy is unknown. We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti‐programmed death‐ligand 1 (PD‐L1) antibody for advanced non‐small‐cell lung cancer. The anti‐interleukin‐5 antibody, mepolizumab, was introduced, resulting in the discontinuation of systemic prednisolone and good asthma control. These reports suggest that treatment with biologics may be effective in severe cases of poorly controlled bronchial asthma during ICI therapy. [ABSTRACT FROM AUTHOR]

A 51-year-old woman had an incidental finding of a tracheal tumor during oesophagogastroduodenoscopy following the diagnosis of asthma for 2 months. A computed tomography scan revealed a 15-mm tumor in the subglottis. Endoscopic resection was performed safely, and pleomorphic adenoma was diagnosed histologically. The patient's condition was satisfactory 30 months after the procedure. Tracheal pleomorphic adenoma is rare and may be misdiagnosed as asthma. If the tumor is large, surgery may be required; however, endoscopic polypectomy may be effective if the tumor is small. Therefore, early diagnosis of tracheal pleomorphic adenoma is important. At the first visit, the flow–volume curve suggested upper airway obstruction, which should have raised the suspicion of an upper airway obstruction. In patients with suspected asthma, early pulmonary function testing is needed to substantiate asthma diagnosis and prevent an alternative diagnosis being missed. [ABSTRACT FROM AUTHOR]

Key message: Clinicians should be aware that biologic agents, which include polysorbates, can cause delayed local skin reactions at a previous injection site. [ABSTRACT FROM AUTHOR]