Pub Date : 2024-03-27DOI: 10.1016/j.resinv.2024.03.003
Roberta Valeria Latorre , Martina Calicchia , Martina Bigliardi , Jessica Conti , Karina Kleinfelder , Paola Melotti , Claudio Sorio
Background
Many disease-causing variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene remain uncharacterized and untreated. Restoring the function of the impaired CFTR protein is the goal of personalized medicine, particularly in patients carrying rare CFTR variants. In this study, functional defects related to the rare R334W variant were evaluated after treatment with CFTR modulators or Roflumilast, a phosphodiesterase-4 inhibitor (PDE4i).
Methods
Rectal organoids from subjects with R334W/2184insA and R334W/2183AA > G genotypes were used to perform the Forskolin-induced swelling (FIS) assay. Organoids were left drug-untreated or treated with modulators VX-770 (I), VX-445 (E), and VX-661 (T) mixed, and their combination (ETI). Roflumilast (R) was used alone or as a combination of I + R.
Results
Our data show a significant increase in FIS rate following treatment with I alone. The combined use of modulators, such as ETI, did not increase further swelling than I alone, nor in protein maturation. Treatment with R shows an increase in FIS response similar to those of I, and the combination R + I significantly increases the rescue of CFTR activity.
Conclusions
Equivalent I and ETI treatment efficacy was observed for both genotypes. Furthermore, significant organoid swelling was observed with combined I + R used that supports the recently published data describing a potentiating effect of only I in patients carrying the variant R334W and, at the same time, corroborating the role of strategies that include PDE4 inhibitors further to potentiate the effect of I for this variant.
背景囊性纤维化跨膜传导调节器(CFTR)基因中的许多致病变体仍未定性和治疗。恢复受损的 CFTR 蛋白的功能是个性化医疗的目标,尤其是对于携带罕见 CFTR 变异基因的患者。在这项研究中,使用 CFTR 调节剂或磷酸二酯酶-4 抑制剂(PDE4i)罗氟司特治疗后,对与罕见 R334W 变异相关的功能缺陷进行了评估。有机体未经药物处理或用调节剂 VX-770 (I)、VX-445 (E) 和 VX-661 (T) 混合处理,以及它们的组合 (ETI) 处理。结果我们的数据显示,单独使用 I 治疗后,FIS 率显著增加。与单独使用 I 相比,联合使用 ETI 等调节剂不会进一步增加肿胀,也不会增加蛋白质成熟。R 的治疗显示 FIS 反应的增加与 I 相似,而 R + I 的组合则显著增加了对 CFTR 活性的挽救。此外,联合使用 I + R 还观察到明显的器官肿胀,这支持了最近发表的数据,该数据描述了仅 I 对携带 R334W 变体的患者的增效作用,同时也证实了包括 PDE4 抑制剂在内的策略在进一步增强 I 对该变体的作用方面所起的作用。
{"title":"Functional rescue of CFTR in rectal organoids from patients carrying R334W variant by CFTR modulators and PDE4 inhibitor Roflumilast","authors":"Roberta Valeria Latorre , Martina Calicchia , Martina Bigliardi , Jessica Conti , Karina Kleinfelder , Paola Melotti , Claudio Sorio","doi":"10.1016/j.resinv.2024.03.003","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><p>Many disease-causing variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene remain uncharacterized and untreated. Restoring the function of the impaired CFTR protein is the goal of personalized medicine, particularly in patients carrying rare CFTR variants. In this study, functional defects related to the rare R334W variant were evaluated after treatment with CFTR modulators or Roflumilast, a phosphodiesterase-4 inhibitor (PDE4i).</p></div><div><h3>Methods</h3><p>Rectal organoids from subjects with R334W/2184insA and R334W/2183AA > G genotypes were used to perform the Forskolin-induced swelling (FIS) assay. Organoids were left drug-untreated or treated with modulators VX-770 (I), VX-445 (E), and VX-661 (T) mixed, and their combination (ETI). Roflumilast (R) was used alone or as a combination of I + R.</p></div><div><h3>Results</h3><p>Our data show a significant increase in FIS rate following treatment with I alone. The combined use of modulators, such as ETI, did not increase further swelling than I alone, nor in protein maturation. Treatment with R shows an increase in FIS response similar to those of I, and the combination R + I significantly increases the rescue of CFTR activity.</p></div><div><h3>Conclusions</h3><p>Equivalent I and ETI treatment efficacy was observed for both genotypes. Furthermore, significant organoid swelling was observed with combined I + R used that supports the recently published data describing a potentiating effect of only I in patients carrying the variant R334W and, at the same time, corroborating the role of strategies that include PDE4 inhibitors further to potentiate the effect of I for this variant.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212534524000455/pdfft?md5=4279dafc7c81abfb1093f615fe2ade1d&pid=1-s2.0-S2212534524000455-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140296434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The endobronchial silicone spigot, also known as the endobronchial Watanabe spigot, is used in bronchoscopic interventions to manage prolonged pulmonary air leakage. However, the outcomes of this procedure have not been thoroughly investigated.
Methods
Using a Japanese national inpatient database from April 2014 to March 2022, we assessed the clinical characteristics and outcomes of all eligible patients who received the endobronchial spigot. We also investigated risk factors associated with treatment failure. Treatment failure was defined as in-hospital death or the need for surgery after bronchial occlusion.
Results
We analyzed data of 1095 patients who underwent bronchial occlusion using the endobronchial spigot. Among them, 252 patients (23.0%) died during hospitalization, and 403 patients (36.8%) experienced treatment failure. Factors associated with treatment failure included age between 85 and 94 years (odds ratio [OR] 1.83; 95% confidence intervals [CI], 1.04–3.21); male sex (OR 2.43; 95% CI, 1.44–4.11); low Barthel index score; comorbidities of interstitial pneumonia (OR 1.71; 95% CI, 1.18–2.48); antibiotics treatment (OR 1.45; 95% CI, 1.02–2.07); steroids treatment (OR 1.59; 95% CI, 1.07–2.36); and surgery prior to bronchial occlusion (OR 2.08; 95% CI, 1.29–3.35). In contrast, pleurodesis after bronchial occlusion (OR 0.49; 95% CI, 0.32–0.75), and admission to high-volume hospitals were inversely associated with treatment failure (OR 0.58; 95% CI, 0.37–0.90).
Conclusions
The endobronchial Watanabe spigot could be a nonsurgical treatment option for patients with prolonged pulmonary air leaks. Our findings will help identify patients who may benefit from such bronchial interventions.
{"title":"Endobronchial silicone spigot in prolonged air leaks: Nationwide study on outcomes and risk factors for treatment failure","authors":"Jumpei Taniguchi , Shotaro Aso , Jo Taisuke , Hiroki Matsui , Kiyohide Fushimi , Hideo Yasunaga","doi":"10.1016/j.resinv.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.03.004","url":null,"abstract":"<div><h3>Background</h3><p>The endobronchial silicone spigot, also known as the endobronchial Watanabe spigot, is used in bronchoscopic interventions to manage prolonged pulmonary air leakage. However, the outcomes of this procedure have not been thoroughly investigated.</p></div><div><h3>Methods</h3><p>Using a Japanese national inpatient database from April 2014 to March 2022, we assessed the clinical characteristics and outcomes of all eligible patients who received the endobronchial spigot. We also investigated risk factors associated with treatment failure. Treatment failure was defined as in-hospital death or the need for surgery after bronchial occlusion.</p></div><div><h3>Results</h3><p>We analyzed data of 1095 patients who underwent bronchial occlusion using the endobronchial spigot. Among them, 252 patients (23.0%) died during hospitalization, and 403 patients (36.8%) experienced treatment failure. Factors associated with treatment failure included age between 85 and 94 years (odds ratio [OR] 1.83; 95% confidence intervals [CI], 1.04–3.21); male sex (OR 2.43; 95% CI, 1.44–4.11); low Barthel index score; comorbidities of interstitial pneumonia (OR 1.71; 95% CI, 1.18–2.48); antibiotics treatment (OR 1.45; 95% CI, 1.02–2.07); steroids treatment (OR 1.59; 95% CI, 1.07–2.36); and surgery prior to bronchial occlusion (OR 2.08; 95% CI, 1.29–3.35). In contrast, pleurodesis after bronchial occlusion (OR 0.49; 95% CI, 0.32–0.75), and admission to high-volume hospitals were inversely associated with treatment failure (OR 0.58; 95% CI, 0.37–0.90).</p></div><div><h3>Conclusions</h3><p>The endobronchial Watanabe spigot could be a nonsurgical treatment option for patients with prolonged pulmonary air leaks. Our findings will help identify patients who may benefit from such bronchial interventions.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140191162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients’ quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted.
Methods
Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered.
Results
A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor.
Conclusions
We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.
{"title":"Prevalence and causes of chronic cough in Japan","authors":"Yoshihisa Ishiura , Masaki Fujimura , Haruhiko Ogawa , Johsuke Hara , Hiromoto Shintani , Soichiro Hozawa , Ryo Atsuta , Kensuke Fukumitsu , Hideki Inoue , Takanobu Shioya , Masato Muraki , Tokunao Amemiya , Noriyuki Ohkura , Yoshitaka Oribe , Hiroshi Tanaka , Takechiyo Yamada , Mikio Toyoshima , Katsuya Fujimori , Tamotsu Ishizuka , Manabu Kagaya , Akio Niimi","doi":"10.1016/j.resinv.2024.02.017","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.017","url":null,"abstract":"<div><h3>Background</h3><p>Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients’ quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted.</p></div><div><h3>Methods</h3><p>Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered.</p></div><div><h3>Results</h3><p>A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor.</p></div><div><h3>Conclusions</h3><p>We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221253452400042X/pdfft?md5=f17a6e735363aaf191b067b91aa982be&pid=1-s2.0-S221253452400042X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A 51-year-old man with advanced lung cancer underwent chemotherapy including an immune checkpoint inhibitor (ICI). Subsequently, he developed ICI-related pneumonitis and colitis, followed by a ten-month treatment course of high doses of steroids. An infection with the SARS-CoV-2 Omicron BA.5 variant caused lethal respiratory failure. Autopsy examination revealed no evidence of viable lung cancer cells in the evaluated organs including the lungs, suggesting that pathological complete response (pCR) could be successfully achieved by ICI treatment in advanced lung cancer patients.
Recognizing steroid-resistant ICI-related adverse events as critical factors in severe COVID-19 emphasizes the need for appropriate assessment of ICI-induced pCR.
{"title":"Autopsy case: Pathological complete response in an advanced lung cancer patient with severe immune related adverse events and COVID-19","authors":"Ryoma Moriya , Naoki Kamihata , Yoshikazu Niwa , Hisashi Kako , Hideaki Takahashi , Yutaro Kimura , Yoshiko Shigeyasu , Tetsuya Tsukamoto , Naozumi Hashimoto , Kazuyoshi Imaizumi","doi":"10.1016/j.resinv.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.03.002","url":null,"abstract":"<div><p>A 51-year-old man with advanced lung cancer underwent chemotherapy including an immune checkpoint inhibitor (ICI). Subsequently, he developed ICI-related pneumonitis and colitis, followed by a ten-month treatment course of high doses of steroids. An infection with the SARS-CoV-2 Omicron BA.5 variant caused lethal respiratory failure. Autopsy examination revealed no evidence of viable lung cancer cells in the evaluated organs including the lungs, suggesting that pathological complete response (pCR) could be successfully achieved by ICI treatment in advanced lung cancer patients.</p><p>Recognizing steroid-resistant ICI-related adverse events as critical factors in severe COVID-19 emphasizes the need for appropriate assessment of ICI-induced pCR.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biologics are clinically available for patients with severe asthma, but changes in asthma control over time are unknown. We examined changes in disease burden and treatment in severe asthma patients.
Methods
This retrospective study used a Japanese health insurance database (Cross Fact) and included patients aged ≥16 years treated continuously with an inhaled corticosteroid (ICS) for a diagnosis of asthma in each calendar year from 2015 to 2019. Severe asthma was defined as annual use of high-dose ICS plus one or more asthma controller medications four or more times, oral corticosteroids for ≥183 days, or biologics for ≥16 weeks. Changes in asthma exacerbations, prescriptions, and laboratory testing were examined.
Results
Demographic characteristics were similar throughout the study. The number and proportion of patients with severe asthma among those with asthma increased (2724; 15.3% in 2015 vs 4485; 19.0% in 2019). The proportion of severe asthma patients with two or more asthma exacerbations decreased from 24.4% to 21.5%. Odds ratios (95% confidence interval) of ≥2 asthma exacerbations in each year compared with 2015 were 0.96 (0.85–1.08) in 2016 and 0.86 (0.76–0.97) in 2017, with significant reductions observed in subsequent years. Short-acting beta agonists and oral corticosteroid prescriptions for asthma exacerbations decreased and long-acting muscarinic antagonist and biologic prescriptions for maintenance treatment increased.
Conclusions
This study showed improvements in disease burden and treatment in severe asthma patients. There remains an unmet medical need for patients with severe asthma, given the proportion who continue to have asthma exacerbations.
{"title":"Changes in disease burden and treatment reality in patients with severe asthma","authors":"Hiroyuki Nagase , Hayato Oka , Hitomi Uchimura , Yoshifumi Arita , Takehiro Hirai , Naoyuki Makita , Naoki Tashiro , Kazuto Matsunaga","doi":"10.1016/j.resinv.2024.02.007","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.007","url":null,"abstract":"<div><h3>Background</h3><p>Biologics are clinically available for patients with severe asthma, but changes in asthma control over time are unknown. We examined changes in disease burden and treatment in severe asthma patients.</p></div><div><h3>Methods</h3><p>This retrospective study used a Japanese health insurance database (Cross Fact) and included patients aged ≥16 years treated continuously with an inhaled corticosteroid (ICS) for a diagnosis of asthma in each calendar year from 2015 to 2019. Severe asthma was defined as annual use of high-dose ICS plus one or more asthma controller medications four or more times, oral corticosteroids for ≥183 days, or biologics for ≥16 weeks. Changes in asthma exacerbations, prescriptions, and laboratory testing were examined.</p></div><div><h3>Results</h3><p>Demographic characteristics were similar throughout the study. The number and proportion of patients with severe asthma among those with asthma increased (2724; 15.3% in 2015 vs 4485; 19.0% in 2019). The proportion of severe asthma patients with two or more asthma exacerbations decreased from 24.4% to 21.5%. Odds ratios (95% confidence interval) of ≥2 asthma exacerbations in each year compared with 2015 were 0.96 (0.85–1.08) in 2016 and 0.86 (0.76–0.97) in 2017, with significant reductions observed in subsequent years. Short-acting beta agonists and oral corticosteroid prescriptions for asthma exacerbations decreased and long-acting muscarinic antagonist and biologic prescriptions for maintenance treatment increased.</p></div><div><h3>Conclusions</h3><p>This study showed improvements in disease burden and treatment in severe asthma patients. There remains an unmet medical need for patients with severe asthma, given the proportion who continue to have asthma exacerbations.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.1016/j.resinv.2024.03.001
Yusuke Okubo , Kazuhiro Uda
Background
This study explored factors associated with testing and diagnoses for children with COVID-19 at the hospital level and investigated whether the capacity of testing and diagnoses during the 2009 influenza pandemic was associated with that during COVID-19 pandemic.
Methods
In this observational study, we analyzed data obtained from the Japan Medical Data Center database, comprising 4906 medical facilities and 1.7 million infectious disease-related visits among children aged <20 years in 2020–2021. Multivariable generalized linear models were used to explore determinants of testing and diagnoses capacity for COVID-19 and investigate the association between the capacity during the 2009 influenza and COVID-19 pandemics.
Results
Public hospitals (adjusted incidence rate ratio [aIRR], 1.52; 95%CI, 1.26–1.82) and university hospitals (aIRR, 1.44; 95%CI, 1.14–1.80) were more likely to perform testing for COVID-19 among children, compared to clinics. The highest testing rate was observed in the department of internal medicine (aIRR, 1.64; 95%CI, 1.32–2.04), followed by pediatrics (aIRR, 1.40; 95%CI, 1.10–1.78) and otolaryngology (aIRR, 1.21; 95%CI, 0.89–1.64). Cubic spline models demonstrated the dose-response relationships between testing rate for influenza in 2009 and testing rates for COVID-19. Compared to the medical facilities in the lowest quartile of testing rate for influenza in 2009, those in the highest quartile were more likely to perform testing for COVID-19 (aIRR, 1.62; 95%CI, 1.43–1.83).
Conclusions
Our study provides insights into the capacity of testing and diagnoses for children, highlighting the dose-response relationship between the 2009 influenza and COVID-19 pandemics, which could be valuable in preparing healthcare systems for future pandemics.
{"title":"Structural and organizational determinants of the capacity for COVID-19 testing and diagnoses in children: Insights from the 2009 influenza and COVID-19 pandemics","authors":"Yusuke Okubo , Kazuhiro Uda","doi":"10.1016/j.resinv.2024.03.001","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>This study explored factors associated with testing and diagnoses for children with COVID-19 at the hospital level and investigated whether the capacity of testing and diagnoses during the 2009 influenza pandemic was associated with that during COVID-19 pandemic.</p></div><div><h3>Methods</h3><p>In this observational study, we analyzed data obtained from the Japan Medical Data Center database, comprising 4906 medical facilities and 1.7 million infectious disease-related visits among children aged <20 years in 2020–2021. Multivariable generalized linear models were used to explore determinants of testing and diagnoses capacity for COVID-19 and investigate the association between the capacity during the 2009 influenza and COVID-19 pandemics.</p></div><div><h3>Results</h3><p>Public hospitals (adjusted incidence rate ratio [aIRR], 1.52; 95%CI, 1.26–1.82) and university hospitals (aIRR, 1.44; 95%CI, 1.14–1.80) were more likely to perform testing for COVID-19 among children, compared to clinics. The highest testing rate was observed in the department of internal medicine (aIRR, 1.64; 95%CI, 1.32–2.04), followed by pediatrics (aIRR, 1.40; 95%CI, 1.10–1.78) and otolaryngology (aIRR, 1.21; 95%CI, 0.89–1.64). Cubic spline models demonstrated the dose-response relationships between testing rate for influenza in 2009 and testing rates for COVID-19. Compared to the medical facilities in the lowest quartile of testing rate for influenza in 2009, those in the highest quartile were more likely to perform testing for COVID-19 (aIRR, 1.62; 95%CI, 1.43–1.83).</p></div><div><h3>Conclusions</h3><p>Our study provides insights into the capacity of testing and diagnoses for children, highlighting the dose-response relationship between the 2009 influenza and COVID-19 pandemics, which could be valuable in preparing healthcare systems for future pandemics.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14DOI: 10.1016/j.resinv.2024.02.014
Masashi Bando , Sakae Homma , Hiroshi Date , Kazuma Kishi , Hiroyoshi Yamauchi , Susumu Sakamoto , Atsushi Miyamoto , Yoshihito Goto , Takeo Nakayama , Arata Azuma , Yasuhiro Kondoh , Takeshi Johkoh , Yasuhiko Nishioka , Junya Fukuoka , Yasunari Miyazaki , Ichiro Yoshino , Takafumi Suda , the Ministry of Health, Labour and Welfare, the Study Group on Diffuse Pulmonary Disorders, Scientific Research/Research on Intractable Diseases, and Japanese Respiratory Society
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines."
Because new evidence had accumulated, we formulated the “Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition).” While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.
{"title":"Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition","authors":"Masashi Bando , Sakae Homma , Hiroshi Date , Kazuma Kishi , Hiroyoshi Yamauchi , Susumu Sakamoto , Atsushi Miyamoto , Yoshihito Goto , Takeo Nakayama , Arata Azuma , Yasuhiro Kondoh , Takeshi Johkoh , Yasuhiko Nishioka , Junya Fukuoka , Yasunari Miyazaki , Ichiro Yoshino , Takafumi Suda , the Ministry of Health, Labour and Welfare, the Study Group on Diffuse Pulmonary Disorders, Scientific Research/Research on Intractable Diseases, and Japanese Respiratory Society","doi":"10.1016/j.resinv.2024.02.014","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.014","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The \"Guidelines for the treatment of idiopathic pulmonary fibrosis 2017,\" specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of \"Formulation procedure for Minds Clinical Practice Guidelines.\"</p><p>Because new evidence had accumulated, we formulated the “Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition).” While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140123052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciliary beat frequency (CBF) is crucial in mucociliary clearance. High-speed video analysis (HSVA) is commonly used to measure CBF but lacks standardization. We compared visual observation and computer-assisted calculation using fast Fourier transformation (FFT) in freshly collected bronchial ciliary epithelial cells and cultured cells.
Methods
Bronchial epithelial cells were obtained from 12 patients who required bronchoscopic examination. Eighty-five videos of ciliary movement of freshly collected and cultured cells were recorded and used to calculate CBF using manual observation, region of interest (ROI) selection, and whole-field analysis.
Results
CBF measured by the ROI selection method strongly correlated with that measured using manual observation, especially in freshly collected cells. However, 27.8% of the manual observation method values were doubled in the ROI selection method, probably because a round trip of cilia was calculated as two cycles and needed to be corrected to 1/2 value. Upon increasing the number of ROIs, the results of the ROI selection method came closer to that of WFA.
Conclusions
Computer-assisted calculation using FFT can aid in measuring CBF; however, current methods require visual confirmation. Further automated evaluation techniques are needed to establish more standardized and generalized CBF measurement methods using HSVA.
{"title":"Comparing region of interest selection and whole-field analysis for measurement of ciliary beat frequency in high-speed video analysis","authors":"Miki Abo , Kousuke Imamura , Shigekuni Hosogi , Takafumi Kobayashi , Yoshihiro Takeda , Kazumasa Kase , Hayato Koba , Satoshi Watanabe , Noriyuki Ohkura , Johsuke Hara , Seiji Yano","doi":"10.1016/j.resinv.2024.02.016","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.016","url":null,"abstract":"<div><h3>Background</h3><p>Ciliary beat frequency (CBF) is crucial in mucociliary clearance. High-speed video analysis (HSVA) is commonly used to measure CBF but lacks standardization. We compared visual observation and computer-assisted calculation using fast Fourier transformation (FFT) in freshly collected bronchial ciliary epithelial cells and cultured cells.</p></div><div><h3>Methods</h3><p>Bronchial epithelial cells were obtained from 12 patients who required bronchoscopic examination. Eighty-five videos of ciliary movement of freshly collected and cultured cells were recorded and used to calculate CBF using manual observation, region of interest (ROI) selection, and whole-field analysis.</p></div><div><h3>Results</h3><p>CBF measured by the ROI selection method strongly correlated with that measured using manual observation, especially in freshly collected cells. However, 27.8% of the manual observation method values were doubled in the ROI selection method, probably because a round trip of cilia was calculated as two cycles and needed to be corrected to 1/2 value. Upon increasing the number of ROIs, the results of the ROI selection method came closer to that of WFA.</p></div><div><h3>Conclusions</h3><p>Computer-assisted calculation using FFT can aid in measuring CBF; however, current methods require visual confirmation. Further automated evaluation techniques are needed to establish more standardized and generalized CBF measurement methods using HSVA.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140123059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Guidelines for the Management of Cough and Sputum (2019) of the Japanese Respiratory Society (JRS) were the first internationally published guidelines for the management of sputum. However, the data used to determine the causative diseases of bloody sputum and hemoptysis in these guidelines were not obtained in Japan.
Methods
A retrospective analysis was performed using the clinical information of patients with bloody sputum or hemoptysis who visited the department of respiratory medicine at a university or core hospital in Japan.
Results
Included in the study were 556 patients (median age, 73 years; age range, 21–98 years; 302 males (54.3%)). The main causative diseases were bronchiectasis (102 patients (18.3%)), lung cancer (97 patients (17.4%)), and non-tuberculous mycobacterial disease (89 patients (16%)). Sex and age differences were observed in the frequency of causative diseases of bloody sputum and hemoptysis. The most common cause was lung cancer in males (26%), bronchiectasis in females (29%), lung cancer in patients aged <65 years (19%), and bronchiectasis in those aged >65 years (20%).
Conclusions
The present study is the first to investigate the causative diseases of bloody sputum and hemoptysis using data obtained in Japan. When investigating the causative diseases of bloody sputum and hemoptysis, it is important to take the sex and age of the patients into account.
{"title":"Nationwide survey in Japan of the causative diseases of bloody sputum and hemoptysis in departments of respiratory medicine at university hospitals and core hospitals","authors":"Hiroaki Fujii , Yu Hara , Yasushi Obase , Shusaku Haranaga , Hidenori Takahashi , Masaharu Shinkai , Jiro Terada , Jun Ikari , Hideki Katsura , Kazuko Yamamoto , Takuji Suzuki , Etsuko Tagaya , Hiroshi Mukae , Takeshi Kaneko","doi":"10.1016/j.resinv.2024.02.003","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.003","url":null,"abstract":"<div><h3>Background</h3><p>The Guidelines for the Management of Cough and Sputum (2019) of the Japanese Respiratory Society (JRS) were the first internationally published guidelines for the management of sputum. However, the data used to determine the causative diseases of bloody sputum and hemoptysis in these guidelines were not obtained in Japan.</p></div><div><h3>Methods</h3><p>A retrospective analysis was performed using the clinical information of patients with bloody sputum or hemoptysis who visited the department of respiratory medicine at a university or core hospital in Japan.</p></div><div><h3>Results</h3><p>Included in the study were 556 patients (median age, 73 years; age range, 21–98 years; 302 males (54.3%)). The main causative diseases were bronchiectasis (102 patients (18.3%)), lung cancer (97 patients (17.4%)), and non-tuberculous mycobacterial disease (89 patients (16%)). Sex and age differences were observed in the frequency of causative diseases of bloody sputum and hemoptysis. The most common cause was lung cancer in males (26%), bronchiectasis in females (29%), lung cancer in patients aged <65 years (19%), and bronchiectasis in those aged >65 years (20%).</p></div><div><h3>Conclusions</h3><p>The present study is the first to investigate the causative diseases of bloody sputum and hemoptysis using data obtained in Japan. When investigating the causative diseases of bloody sputum and hemoptysis, it is important to take the sex and age of the patients into account.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212534524000285/pdfft?md5=42c1357e384fdd4c193d1bb8e40b651c&pid=1-s2.0-S2212534524000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The antifibrotic agents pirfenidone and nintedanib have been shown to be effective in patients with idiopathic pulmonary fibrosis (IPF). However, discontinuation of antifibrotic drugs is a major clinical concern because of the lack of alternative treatment options. Therefore, we identified factors that may be useful for predicting the termination of antifibrotic agents.
Methods
We retrospectively recruited 280 IPF patients treated with antifibrotic drugs between 2009 and 2018 from seven regional core hospitals in Gunma prefecture, Japan. Results: At four months, the short-term discontinuation group exhibited a significantly worse prognosis in the pirfenidone group and a poorer prognosis in the nintedanib group compared to that in the continuation group. The discontinuation group of pirfenidone at 4 months exhibited lower albumin and higher C-reactive protein (CRP) levels in the sera compared to the group that continued treatment for more than 4 months. In multivariate analysis, the Glasgow prognostic score (GPS), well known as a predictor of cancer prognosis, which comprises serum CRP and albumin levels, predicted early discontinuation and prognosis in the pirfenidone group, whereas the body mass index (BMI) predicted early discontinuation of nintedanib. A high GPS, with both albumin <3.5 g/dL and CRP >1.0 mg/dL, was associated with a poorer prognosis in the pirfenidone group.
Conclusion
GPS and BMI were significant factors for short-term pirfenidone and nintedanib discontinuation, respectively. Initial evaluation of GPS and BMI prior to antifibrotic therapy may contribute to less interrupted IPF management, thus leading to better prognostic outcomes in patients with IPF.
{"title":"Glasgow prognostic score and body mass index predict short-term discontinuation of the antifibrotic agents pirfenidone and nintedanib","authors":"Kazutaka Takehara , Yasuhiko Koga , Yoshimasa Hachisu , Mitsuyoshi Utsugi , Yuri Sawada , Yasuyuki Saito , Seishi Yoshimi , Masakiyo Yatomi , Hiroaki Tsurumaki , Yuki Shin , Ikuo Wakamatsu , Norimitsu Kasahara , Koichi Yamaguchi , Kazue Umetsu , Shunichi Kouno , Junichi Nakagawa , Noriaki Sunaga , Toshitaka Maeno , Takeshi Hisada","doi":"10.1016/j.resinv.2024.02.012","DOIUrl":"https://doi.org/10.1016/j.resinv.2024.02.012","url":null,"abstract":"<div><h3>Background</h3><p>The antifibrotic agents pirfenidone and nintedanib have been shown to be effective in patients with idiopathic pulmonary fibrosis (IPF). However, discontinuation of antifibrotic drugs is a major clinical concern because of the lack of alternative treatment options. Therefore, we identified factors that may be useful for predicting the termination of antifibrotic agents.</p></div><div><h3>Methods</h3><p>We retrospectively recruited 280 IPF patients treated with antifibrotic drugs between 2009 and 2018 from seven regional core hospitals in Gunma prefecture, Japan. <strong>Results</strong>: At four months, the short-term discontinuation group exhibited a significantly worse prognosis in the pirfenidone group and a poorer prognosis in the nintedanib group compared to that in the continuation group. The discontinuation group of pirfenidone at 4 months exhibited lower albumin and higher C-reactive protein (CRP) levels in the sera compared to the group that continued treatment for more than 4 months. In multivariate analysis, the Glasgow prognostic score (GPS), well known as a predictor of cancer prognosis, which comprises serum CRP and albumin levels, predicted early discontinuation and prognosis in the pirfenidone group, whereas the body mass index (BMI) predicted early discontinuation of nintedanib. A high GPS, with both albumin <3.5 g/dL and CRP >1.0 mg/dL, was associated with a poorer prognosis in the pirfenidone group.</p></div><div><h3>Conclusion</h3><p>GPS and BMI were significant factors for short-term pirfenidone and nintedanib discontinuation, respectively. Initial evaluation of GPS and BMI prior to antifibrotic therapy may contribute to less interrupted IPF management, thus leading to better prognostic outcomes in patients with IPF.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}