{"title":"Efficacy and safety of mucolytics in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis","authors":"Hiroshi Ohnishi , Takuya Tanimoto , Ryunosuke Inaba , Masamitsu Eitoku","doi":"10.1016/j.resinv.2024.10.004","DOIUrl":"10.1016/j.resinv.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>The efficacy and safety of mucolytics in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis or exacerbations of COPD have been reported. We conducted a systematic review and meta-analysis of mucolytics in patients with stable COPD.</div></div><div><h3>Methods</h3><div>Reports from randomized controlled trials to evaluate the efficacy and safety of mucolytics, including ambroxol, bromhexine, carbocisteine, erdosteine, fudosteine, <span>l</span>-methylcysteine, and N-acetylcysteine used in patients with stable COPD were searched for in PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and the Igaku Cyuo Zasshi database.</div></div><div><h3>Results</h3><div>Twenty-three reports with ambroxol, carbocisteine, erdosteine, <span>l</span>-methylcysteine, or N-acetylcysteine were included in the review. Mucolytics significantly reduced the rates of exacerbation and hospitalization, shortened the duration of antibiotic use and exacerbations, prolonged the time to first exacerbation, and had a tendency to reduce the occurrence of two or more exacerbations in patients with stable COPD compared to placebo. Mucolytics did not improve mortality, number of lost workdays, scores on St. George's respiratory questionnaire, forced expiratory volume in 1 s, or forced vital capacity. The safety profile of mucolytics was comparable to that of placebo.</div></div><div><h3>Conclusions</h3><div>Mucolytics reduce exacerbations and hospitalizations in patients with stable COPD and have a safety profile comparable to that of placebo.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1168-1175"},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432958","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}
{"title":"Pulmonary fibrosis in pulmonary alveolar proteinosis evaluated by transbronchial lung cryobiopsy: A single-center retrospective study","authors":"Kensuke Kanaoka , Toru Arai , Takayuki Takimoto , Mitsuhiro Moda , Ryota Shintani , Misaki Ryuge , Naoko Takeuchi , Tomoko Kagawa , Kazunobu Tachibana , Yoshikazu Inoue , Hiromitsu Sumikawa , Maiko Takeda , Shigeki Shimizu","doi":"10.1016/j.resinv.2024.10.002","DOIUrl":"10.1016/j.resinv.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Approximately 20% of patients with pulmonary alveolar proteinosis (PAP) present with pulmonary fibrosis on high-resolution computed tomography (HRCT). Although transbronchial lung cryobiopsy (TBLC) has recently been used to diagnose fibrotic interstitial lung disease, no studies have investigated whether TBLC is useful for the histopathological detection of pulmonary fibrosis coexisting with PAP. Therefore, the present study aimed to investigate the utility of TBLC for evaluating pulmonary fibrosis in patients with PAP.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed patients diagnosed with PAP who underwent TBLC at our hospital between May 2021 and March 2023. We collected data including patient background, HRCT findings, and histopathological findings of the TBLC samples.</div></div><div><h3>Results</h3><div>Seven patients met the inclusion criteria, with a median age was 69 years; 5 patients were male. Six patients were diagnosed with autoimmune PAP, and one was diagnosed with unclassified PAP. Periodic acid-Schiff staining-positive materials in the alveoli were observed in six out of seven patients. Pulmonary fibrosis, defined as fibrosis with architectural distortion, was found in two patients. Fibroblastic foci and airway-centered fibrosis were presented in two and one patient, respectively. As a result of a multidisciplinary discussion, we diagnosed one each with fibrotic HP coexisting with PAP and PAP-associated fibrosis.</div></div><div><h3>Conclusion</h3><div>Two of the seven patients with PAP presented histopathologically with pulmonary fibrosis in samples obtained through TBLC. Thus, TBLC should be considered when the coexistence of pulmonary fibrosis is suspected.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425027","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}
{"title":"Therapeutic effects of an ALK inhibitor, brigatinib, on lung large cell neuroendocrine carcinoma with EML4-ALK fusion","authors":"Takayuki Suetsugu , Yutaka Masada , Tomoki Kozono , Kahoru Morita , Hajime Yonezawa , Kazuhiro Tabata , Naohiko Seki , Keiko Mizuno , Kentaro Tanaka , Hiromasa Inoue","doi":"10.1016/j.resinv.2024.09.013","DOIUrl":"10.1016/j.resinv.2024.09.013","url":null,"abstract":"<div><div>A 64-year-old light-smoking woman was clinically diagnosed with lung large-cell neuroendocrine carcinoma (LCNEC) with a metastatic brain tumor. An Oncomine Dx Targeted Test using metastatic brain tissue revealed that the patient's lung cancer cells had an EML4-ALK rearrangement. Patients with LCNEC and anaplastic lymphoma kinase (ALK) gene rearrangements are rare, and there is currently no standard treatment. Based on the genomic analysis, we treated the patient with brigatinib, an ALK inhibitor. We describe here a patient with LCNEC who responded significantly to brigatinib without serious adverse events.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1157-1160"},"PeriodicalIF":2.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425028","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}
Jieun Kang , Ji-Yong Moon , Deog Kyeom Kim , Jin Woo Kim , Seung Hun Jang , Jae-Woo Kwon , Byung-Jae Lee , Hyeon-Kyoung Koo
{"title":"Reclassification of items in the Leicester Cough Questionnaire: Correlation analysis","authors":"Jieun Kang , Ji-Yong Moon , Deog Kyeom Kim , Jin Woo Kim , Seung Hun Jang , Jae-Woo Kwon , Byung-Jae Lee , Hyeon-Kyoung Koo","doi":"10.1016/j.resinv.2024.09.017","DOIUrl":"10.1016/j.resinv.2024.09.017","url":null,"abstract":"<div><h3>Background</h3><div>The Leicester Cough Questionnaire (LCQ) is a validated tool for assessing cough that has three domains (physical, psychological, and social), with eight, seven, and four items, respectively. However, the assigned domain may not accurately reflect the characteristics of an item. This study aimed to reclassify the items in the Korean version of the LCQ (K-LCQ) to improve the coherence in each domain.</div></div><div><h3>Methods</h3><div>Data of patients with chronic cough from 16 centers who completed the K-LCQ were retrospectively analyzed. Spearman’s rank correlation analysis was used to assess the correlations between items and their domains. Principal component analysis was performed to recategorize the K-LCQ items.</div></div><div><h3>Results</h3><div>The correlation analysis of the data from 255 patients demonstrated that certain items such as tiredness, embarrassment, and interference with daily work or overall life enjoyment showed strong or very strong correlations with all three domains. Cough bout frequency showed the weakest correlation with the physical domain, despite being included in that domain, and had stronger correlations with the psychological and social domain. The principal component analysis led to the reclassification of six items: one from the physical to psychological, two from the social to psychological, and three from the psychological to social domain. The within-domain correlation coherence was higher in the new classification than in the original. Validation using an independent cohort of 203 patients yielded similar results.</div></div><div><h3>Conclusions</h3><div>The new classification of the K-LCQ items showed improved within-domain correlation coherence.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1150-1156"},"PeriodicalIF":2.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406723","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}
{"title":"Reassessment of the relevance between microbiological macrolide-induced resistance and diagnosis and treatment outcome of Mycobacterium abscessus-related pulmonary disease","authors":"Shiomi Yoshida , Kazunari Tsuyuguchi , Takehiko Kobayashi , Yu Kurahara , Yasuaki Shimatani , Toru Arai","doi":"10.1016/j.resinv.2024.09.012","DOIUrl":"10.1016/j.resinv.2024.09.012","url":null,"abstract":"<div><h3>Background</h3><div>Treatment outcomes for <em>Mycobacterium abscessus</em> species–related pulmonary disease (MABS-PD) are generally poor because of inducible clarithromycin resistance (IR). The clinical management of patients with MABS with different genotypic and phenotypic susceptibility results is also not definitive. Here, we aimed to reassess the characteristics of patients with variant MABS and their association with diagnosis, treatment intervention, and sputum culture conversion.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 119 patients with MABS infection. Clinical characteristics and medical history were obtained via medical chart review. Isolates were tested for clarithromycin susceptibility and classified into <em>erm</em>(41) sequevars.</div></div><div><h3>Results</h3><div>In the IR, non-IR, and acquired resistance groups, the sputum culture conversion rates were 22% (5/23), 80% (40/50), and 8% (1/12), respectively. In contrast, in MAB, MAB T28, MAB C28, and <em>M. abscessus</em> subsp. <em>massiliense</em> (MAM), sputum culture conversion rates were 33% (12/36), 29% (22/31), 60% (3/5), and 70.8% (34/48), respectively. The proportion of patients with non-IR MAB T28 diagnosed and treated for MABS-PD was lower than those of patients with IR or acquired resistant T28 [35.7% (5/14), 80.7% (21/26), 100% (5/5); <em>P</em> < 0.05], whereas the sputum culture conversion rate was high in patients with non-IR MAB T28 [80.0%(4/5), 23.8%(5/21), 0%(0/5); <em>P</em> < 0.01)]. The sputum culture conversion rate in treated patients with MABS-PD with IR MAB C28 or acquired resistant MAM was low [0.0% (0/1) and 14.3% (1/7)].</div></div><div><h3>Conclusions</h3><div>Patients with MABS-PD and non-IR were likely to have sputum culture conversion. Our results indicated that phenotypical properties were associated with MABS-PD diagnosis and treatment.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1142-1148"},"PeriodicalIF":2.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378218","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}
{"title":"Combined use of serum ferritin and KL-6 levels as biomarkers for predicting COVID-19 severity","authors":"Hiromu Tanaka , Erika Toya , Shotaro Chubachi , Ho Namkoong , Takanori Asakura , Shuhei Azekawa , Shiro Otake , Kensuke Nakagawara , Takahiro Fukushima , Mayuko Watase , Kaori Sakurai , Katsunori Masaki , Hirofumi Kamata , Makoto Ishii , Naoki Hasegawa , Yukinori Okada , Ryuji Koike , Yuko Kitagawa , Akinori Kimura , Seiya Imoto , Koichi Fukunaga","doi":"10.1016/j.resinv.2024.09.011","DOIUrl":"10.1016/j.resinv.2024.09.011","url":null,"abstract":"<div><h3>Objectives</h3><div>To assess the value of serum ferritin and Krebs von den Lungen-6 (KL-6) levels for predicting severe COVID-19 (death or requirement for invasive mechanical ventilation [IMV]/high-flow oxygen).</div></div><div><h3>Methods</h3><div>Data were analyzed on 2495 patients with COVID-19 from February 2020 to November 2022 using data from a nationwide COVID-19 database.</div></div><div><h3>Results</h3><div>Patients with high KL-6 and low ferritin levels were older with more comorbidities and higher mortality rates, whereas those with high ferritin and low KL-6 levels were younger, predominantly male, and more likely to need IMV. A high level of both markers was strongly associated with critical outcomes (adjusted odds ratio: 13.6, 95% confidence interval: 8.58–21.5). The combination of both markers had higher predictive value than either marker alone (area under the curve: 0.709, 0.745, and 0.781 for KL-6, ferritin, and KL-6 + ferritin, respectively).</div></div><div><h3>Conclusions</h3><div>The combination of both markers accurately predicted COVID-19 severity.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1132-1136"},"PeriodicalIF":2.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375883","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}
{"title":"Comparison of efficacy of gefitinib and osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer in patients with poor performance status","authors":"Kazuhisa Nakashima , Hiroaki Kodama , Haruyasu Murakami , Toshiaki Takahashi , Keita Kawakado , Takashi Yanagawa , Kashu Kitani , Takamasa Hottta , Masaaki Abe , Kosuke Hamai , Takuya Tanimoto , Nobuhisa Ishikawa , Tomoki Tamura , Shoichi Kuyama , Takeshi Isobe , Yukari Tsubata","doi":"10.1016/j.resinv.2024.09.010","DOIUrl":"10.1016/j.resinv.2024.09.010","url":null,"abstract":"<div><h3>Background</h3><div>There is a dearth of studies on the efficacy and safety of the tyrosine kinase inhibitors osimertinib (OSI) and gefitinib (GEF) in treating epidermal growth factor receptor (<em>EGFR</em>) mutation-positive non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS).</div></div><div><h3>Methods</h3><div>We retrospectively reviewed and compared data of 113 patients with <em>EGFR</em> mutation-positive NSCLC with Eastern Cooperative Oncology Group PS 2–4 who were administered OSI 80 mg/day or GEF 250 mg/day from May 2016 to March 2022.</div></div><div><h3>Results</h3><div>The GEF group (39 patients; median age: 74 years) included 20 patients with a PS of 2, 17 with a PS of 3, and 2 with a PS of 4. The OSI group (74 patients; median age: 76 years) included 48 patients with a PS of 2, 24 with a PS of 3, and 2 with a PS of 4. The overall response rates were 69% and 66% in the GEF and OSI groups, respectively. The disease control and PS improvement rates were 89% and 51% in both groups, respectively. The median progression-free survival in the GEF and OSI groups was 6.9 and 9.2 months, respectively (p = 0.15). The OSI group experienced better overall survival than the GEF group (median: 20.9 vs. 13.0 months, p = 0.0031). The incidence of pneumonitis was 10% and 11% in the GEF and OSI groups, respectively. One treatment-related death owing to pneumonitis occurred in the GEF group.</div></div><div><h3>Conclusions</h3><div>OSI may be a useful treatment for untreated <em>EGFR</em> mutation-positive NSCLC with poor PS.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1137-1141"},"PeriodicalIF":2.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375884","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}
{"title":"Prevalence and characteristics of minimal pleural fluid on screening chest MRI","authors":"Kensuke Fukuda , Hirotaka Matsuzaki , Takuya Kawahara , Toshihiro Yamaguchi , Akira Saito , Nobutake Yamamichi , Hidenori Kage , Takeharu Yoshikawa","doi":"10.1016/j.resinv.2024.09.014","DOIUrl":"10.1016/j.resinv.2024.09.014","url":null,"abstract":"<div><h3>Background</h3><div>Minimal pleural fluid is often seen incidentally on chest MRI. However, its prevalence and clinical characteristics remain unknown.</div></div><div><h3>Methods</h3><div>This retrospective observational study included 2726 participants who underwent comprehensive medical check-ups for screening, including chest CT and MRI, and transthoracic echocardiography between March 2018 and February 2019. Pleural fluid on MRI was manually measured for maximum thickness. Its distribution, change over time, and relevance to participant characteristics were analyzed. The pulmonary function data of 82 participants and their associations with fluid were also analyzed.</div></div><div><h3>Results</h3><div>Of the 2726 participants (mean age ± standard deviation, 59 ± 11 years), 2009 (73.7%) had minimal pleural fluid (thickness, 1–9 mm) on either side, with right-sided fluid being more frequent than left-sided fluid (<em>P</em> < 0.001). Negligible changes in fluid thickness were observed one year later. The following parameters were associated with less fluid: age, ≥65 years (<em>P</em> < 0.001); male sex (<em>P</em> = 0.006); current smoking (<em>P</em> < 0.001); body mass index, ≥25 kg/m<sup>2</sup> (<em>P</em> < 0.001); and mean arterial pressure, ≥100 mmHg (<em>P</em> = 0.01), whereas a ratio between early mitral inflow velocity and mitral annular early diastolic velocity>14 was associated with more fluid (<em>P</em> = 0.01). The presence of fluid was an independent explanatory variable for a higher percentage of predicted vital capacity (<em>P</em> = 0.048).</div></div><div><h3>Conclusions</h3><div>MRI was highly sensitive in detecting minimal pleural fluid. Pleural fluid found on MRI for health screening was assumed to be physiological and fluid thickness at the steady state might be variable among participants depending on age, sex, smoking habits, body shape, blood pressure, and cardiac diastolic capacity.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1109-1116"},"PeriodicalIF":2.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372709","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}
{"title":"Factors associated with non-intervention of antifibrotic agents in IPF patients","authors":"Maki Asami-Noyama , Kazuki Hamada , Yoshiyuki Asai , Takeshi Abe , Kosei Yonezawa , Michiya Watanabe , Yukari Hisamoto , Keita Murakawa , Ayumi Fukatsu , Kazuki Matsuda , Shuichiro Ohata , Ryo Suetake , Yoriyuki Murata , Yoshikazu Yamaji , Keiji Oishi , Nobutaka Edakuni , Tsunahiko Hirano , Tomoyuki Kakugawa , Kazuto Matsunaga","doi":"10.1016/j.resinv.2024.09.008","DOIUrl":"10.1016/j.resinv.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>The efficacy of antifibrotic agents in idiopathic pulmonary fibrosis (IPF) has been demonstrated and early introduction is recommended, especially in patients with preserved performance status (PS). We aimed to determine the proportion of untreated IPF cases using real-world data and to assess the factors associated with non-intervention.</div></div><div><h3>Methods</h3><div>A prospective observational study using questionnaires was performed on 518 patients with interstitial lung disease (ILD) and their attending physicians who visited a clinic, general hospital, or tertiary respiratory center between December 2019 and October 2020. Patients responded with subjective symptoms and PS, whereas physicians responded with diagnosis, treatment, and reasons for their treatment choices. Principal component analysis (PCA) was performed using age, sex, BMI, medical facility, specialized tests, and symptom severity.</div></div><div><h3>Results</h3><div>We included 207 patients with IPF. Among them, 168 has a good PS (≤2), which could be indicative of treatment; 130 (77.4%) were not treated with antifibrotic agents. The PCA revealed a trend consistent with that of antifibrotic agent therapy and the distribution of medical facilities, with a treatment intervention rate of 16% in general hospitals and 62% in tertiary respiratory centers. In general hospitals, low symptom severity (PS, mMRC, and no use of long-term oxygen therapy) was a relevant factor for non-intervention with antifibrotic agents (p < 0.001).</div></div><div><h3>Conclusion</h3><div>Antifibrotic treatment interventions varied by facility in cases with good PS. Patients with milder symptoms are not being treated early in general hospitals and more collaboration between general hospitals and specialized facilities is necessary.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"62 6","pages":"Pages 1124-1131"},"PeriodicalIF":2.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372725","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}