{"title":"Clinical interpretation of DLCO and KCO: From rationale to clinical and research applications","authors":"Masafumi Yamamoto , Kaoruko Shimizu","doi":"10.1016/j.resinv.2025.02.007","DOIUrl":"10.1016/j.resinv.2025.02.007","url":null,"abstract":"<div><div>Single-breath methods for measuring the diffusing capacity of the lung for carbon monoxide (DL<sub>CO</sub>), Krogh's constant for CO (K<sub>CO</sub>), and alveolar volume (V<sub>A</sub>) play clinically vital roles in assessing lung diffusion. While the methodology is valid for the kinetics of normal lungs, appropriate interpretations are necessary for lung diseases involving emphysema and/or ventilation heterogeneity. Severe airflow limitations and ventilation heterogeneities lead to the underestimation of lung volume, calculated as V<sub>A</sub>, relative to the total lung capacity assessed using the helium closed-circuit method. Notably, the relative increase in K<sub>CO</sub> (DL<sub>CO</sub>/V<sub>A</sub>) compared to DL<sub>CO</sub>—resulting from increased blood flow per alveolar–capillary unit in small lungs with fibrosis—is a distinct feature of interstitial lung disease. Therefore, the combined assessment of DL<sub>CO</sub> and K<sub>CO</sub> may help elucidate the pathophysiology of emphysema and/or pulmonary fibrosis. This review aims to explain Krogh's equation, the difference between DL<sub>CO</sub> and D’L<sub>CO</sub>, the kinetics, and the clinical application of DL<sub>CO</sub> (or D’L<sub>CO</sub>) and K<sub>CO</sub>. Pulmonary function varies among ethnicities and races; thus, reference equations derived while considering anthropological traits are necessary. Additionally, the link between physiological theory, radiological findings, and the clinical relevance of DL<sub>CO</sub> and K<sub>CO</sub> is discussed, mostly based on Japanese studies. In this review, DL<sub>CO</sub> obtained from the single-breath method is referred to as ”D’L<sub>CO</sub>”; however, for convenience, it is described as “DL<sub>CO</sub>,” with the term “D’L<sub>CO</sub>” used only where necessary.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 358-364"},"PeriodicalIF":2.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620889","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":"Resting energy expenditure and associated factors are similar in patients with chronic obstructive pulmonary disease and interstitial lung disease","authors":"Keisuke Morikawa , Hiroyuki Takemura , Kana Kitayama , Shogo Inaba , Haruka Imaoka , Yu Hashitsume , Yuta Suzuki , Osamu Hataji , Kazuyuki Tabira","doi":"10.1016/j.resinv.2025.03.010","DOIUrl":"10.1016/j.resinv.2025.03.010","url":null,"abstract":"<div><h3>Background</h3><div>Few studies have measured the resting energy expenditure (REE) in patients with interstitial lung disease (ILD). Whether REE characteristics in patients with chronic obstructive pulmonary disease (COPD) and ILD are similar remains unknown. We aimed to investigate whether REE and its associated factors were similar in patients with COPD and ILD.</div></div><div><h3>Methods</h3><div>This study included 223 patients (COPD, 102; ILD, 121) who were admitted to our hospital with a diagnosis of COPD or ILD and for whom indirect calorimetry was performed. The measured REE (mREE) was calculated using Weir's formula after indirect calorimetry. Patients with COPD and ILD were classified into two groups by propensity score matching. Multiple regression analysis was used to compare REE between the two groups and examine REE and its associated factors in each group.</div></div><div><h3>Results</h3><div>Body composition and other characteristics differed significantly between the two groups before propensity score matching. Forty-seven patients each were classified into the COPD and ILD groups after propensity score matching. Body mass index was 21.3 ± 3.8 kg/m<sup>2</sup> and 21.2 ± 3.2 kg/m<sup>2</sup> in the COPD and ILD groups, respectively (p = 0.877). The mREE was 1308 ± 204 kcal and 1329 ± 245 kcal in the COPD and ILD groups (p = 0.661). Multiple regression analysis showed that REE was associated with age and FFM in the COPD group and with FFM in the ILD group.</div></div><div><h3>Conclusions</h3><div>FFM plays an important role in determining REE in both diseases, suggesting that REE in patients with COPD and ILD are similar.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 342-345"},"PeriodicalIF":2.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609407","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":"The 6 Minute Walk Test as a predictor of mortality in idiopathic pulmonary fibrosis: A systematic review","authors":"Eugenio Vecchi , Timothy Kilbey , Mihir Sheth , Eleanor Stride , Ashok Handa","doi":"10.1016/j.resinv.2025.03.005","DOIUrl":"10.1016/j.resinv.2025.03.005","url":null,"abstract":"<div><h3>Background</h3><div>The 6-min walk test (6MWT) is frequently used in pulmonary fibrosis (PF) research. It evaluates an individual's sub-maximal exercise performance by measuring the distance they walk and their vital signs across 6 min. In research studies, the 6-min walk distance (6MWD) is often used as a surrogate marker for disease progression. The aim of this study was to systematically assess the association between 6MWT parameters and mortality in PF.</div></div><div><h3>Methods</h3><div>MEDLINE, EMBASE, CINAHL, and CENTRAL databases were searched for studies reporting mortality and 6MWD in patients with PF. Study quality was assessed using a modified Newcastle-Ottawa Scale. Studies were included if they reported associations between the 6MWT in pulmonary fibrosis and mortality. Results were presented as a narrative synthesis.</div></div><div><h3>Results</h3><div>2312 studies were identified, 22 studies met the pre-defined inclusion criteria, comprising 5940 Idiopathic PF patients. Baseline 6MWD was found to be loosely associated with mortality (Ranges: univariate HR 0.89–4.72, multivariate HR 0.96–2.65), while a decrease in 6MWD across 24-weeks was correlated with a higher risk of mortality (Ranges: univariate HR 2.25–4.81, multivariate HR 1.72–4.3).</div></div><div><h3>Discussion</h3><div>This review found that a low baseline 6MWD, and a 6-month decrease in 6MWD were strongly correlated with increased mortality in Idiopathic PF patients. As the 6MWT is a safe, easy-to-conduct test, it is appropriate for use as a marker of patient prognosis, in both clinical and research settings.</div></div><div><h3>Open science framework protocol registration</h3><div>DOI 10.17605/OSF.IO/3D7BV.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 334-341"},"PeriodicalIF":2.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609406","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":"Insights on immune profile, pathogenesis and differential diagnosis of hypersensitivity pneumonitis and pulmonary sarcoidosis-A holistic review and bibliometric analysis","authors":"Sanjukta Dasgupta , Indrani Paul","doi":"10.1016/j.resinv.2025.03.002","DOIUrl":"10.1016/j.resinv.2025.03.002","url":null,"abstract":"<div><div>Hypersensitivity pneumonitis (HP) and sarcoidosis are granulomatous interstitial lung diseases with overlapping clinical and immunological features, posing diagnostic and therapeutic challenges. This review offers a comprehensive assessment of their immune mechanisms, etiology, and pathogenesis.</div><div>HP is predominantly triggered by exposure to environmental antigens, while sarcoidosis involves an exaggerated immune response to elusive antigens. Both diseases are driven by Th1 and Th17 pathways, regulatory T-cell dysfunction, and cytokine-mediated granuloma formation. Emerging diagnostic and prognostic biomarkers, such as KL-6, GDF15, PD-1, TIGIT, and genetic regulators including m6A and m5C modifications, provide valuable insights for disease stratification. Incorporating findings from a total of 38 studies (HP: n = 13; sarcoidosis: n = 25) published in the last 5 years, this review highlights key immune regulatory mechanisms, identifies critical research gaps, and provides directions for improving differential diagnosis. Addressing these gaps through multi-omics integration, computational tools, and interdisciplinary collaboration holds significant potential for refining diagnostic accuracy, advancing therapeutic strategies, and improving patient outcomes in both HP and sarcoidosis.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 346-357"},"PeriodicalIF":2.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609405","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":"Challenges in recognizing airway-centered fibrosis: Observer concordance and its role in fibrotic hypersensitivity pneumonitis","authors":"Kurumi Seki , Jijgee Munkhdelger , Andrey Bychkov , Tomonori Tanaka , Shinobu Kunugi , Ryoko Saito-Koyama , Yukio Kashima , Yoshiaki Zaizen , Koji Okudela , Kensuke Kataoka , Yasuhiko Yamano , Yasuhiro Kondoh , Takeshi Johkoh , Junya Fukuoka","doi":"10.1016/j.resinv.2025.02.001","DOIUrl":"10.1016/j.resinv.2025.02.001","url":null,"abstract":"<div><h3>Background</h3><div>The interobserver agreement regarding airway-centered fibrosis (ACF), the key diagnostic feature of fibrotic hypersensitivity pneumonitis (fHP) has not been sufficiently addressed to date. We applied digital image analysis to investigate this issue and extracted histological features of ACF to correlate with fHP diagnosis.</div></div><div><h3>Methods</h3><div>A total of 111 selected glass slides from 17 fHP and 30 idiopathic pulmonary fibrosis (IPF) were scanned and seven expert pulmonary pathologists were tasked with digital annotation of ACF. Interobserver agreement on annotated ACF was assessed using Fleiss′ kappa value. ACF recognized by majority of pathologists (4 or more) were considered as consensus ACF (cACF), and their frequencies were compared between fHP and IPF cases.</div></div><div><h3>Results</h3><div>Fleiss′ kappa agreement in ACF recognition was 0.32 among seven pathologists. A significant difference between cryobiopsy and VATS specimens regarding an average ACF count per slide (p = 0.012) was found. The number of cACFs in a single case ranged from 0 to 20 (mean 5.71) for fHP cases and 0 to 13 (mean 1.80) for IPF cases (p = 0.011). When limited to surgical biopsies, the average number of cACF was 10.3 for fHP vs. 1.68 for IPF (p < 0.001). The common characteristic features of cACF in fHP were their confinement to the vicinity of respiratory bronchioles, frequent association with peribronchiolar metaplasia, and mild to moderate lymphocytic infiltration.</div></div><div><h3>Conclusions</h3><div>The recognition of ACF varies widely among pathologists. We identified common histologic features of ACF in fHP cases, proposing criteria for ACF recognition in fHP.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 314-321"},"PeriodicalIF":2.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562218","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":"Sarcomatoid pleural mesothelioma evaluated using diffusion-weighted whole-body imaging with background body signal suppression","authors":"Ryosuke Kinoshita , Norihisa Takeda , Hiroko Kiyotoshi , Masahiro Sugihara , Mamiko Kuriyama , Makoto Nakao , Takuji Tsuyuki , Hideki Muramatsu","doi":"10.1016/j.resinv.2025.02.013","DOIUrl":"10.1016/j.resinv.2025.02.013","url":null,"abstract":"<div><div>An 83-year-old man with a history of asbestos exposure presented with dyspnea. Thoracic computed tomography showed right-sided pleural effusion and heterogeneous pleural thickening with calcified plaques. Thoracentesis revealed exudative fluid, and the cytology results were negative for malignancy. He didn't want to undergo invasive biopsy for pathological diagnosis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected signal enhancement in the pleural thickening, ruling out metastasis. The patient died after one month, and sarcomatoid pleural mesothelioma was confirmed by autopsy. DWIBS is free of radioactive materials and can be used to evaluate lesion spread and metastases in hospitals equipped with magnetic resonance imaging.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 323-325"},"PeriodicalIF":2.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562219","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":"The clinical impact of acute vasoreactivity testing in patients with severe pulmonary hypertension associated with lung disease: A retrospective exploratory analysis","authors":"Ryo Takano , Shinya Fujisaki , Hiroyuki Endo , Naruhiro Nishi , Hiroya Hayashi , Takatoyo Kiko , Ryotaro Asano , Jin Ueda , Tatsuo Aoki , Akihiro Tsuji , Takeshi Ogo","doi":"10.1016/j.resinv.2025.02.014","DOIUrl":"10.1016/j.resinv.2025.02.014","url":null,"abstract":"<div><h3>Background</h3><div>The clinical impact of acute vasoreactivity testing with inhaled nitric oxide (NO testing) in severe pulmonary hypertension associated with lung disease (LD-PH) remains unknown.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 48 consecutive patients with severe LD-PH (73 ± 9 years; male: 81%) who underwent NO testing between 2014 and 2022. We conducted an exploratory analysis of the association between the response to NO testing and both the efficacy of pulmonary vasodilators and prognosis.</div></div><div><h3>Results</h3><div>NO testing demonstrated a significant improvement in hemodynamics, with an average reduction of 1.8 wood units in pulmonary vascular resistance (PVR) without a decrease of oxygen saturation. Patients were divided into the vasoreactive and non-vasoreactive groups based on the median PVR response (−15%) to NO testing. The vasoreactive group had a higher proportion of patients who initiated pulmonary vasodilators and had better long-term prognosis than that of the non-vasoreactive group (P = 0.03). Among the 36 patients (75%) who initiated pulmonary vasodilators after NO testing, the vasoreactive group demonstrated a significant improvement in the symptom, brain natriuretic peptide level, and hemodynamics at the first follow-up (median 4 months), whereas the non-vasoreactive group did not. Moreover, a correlation was observed between the change in PVR at NO testing and the change in PVR after initiation of pulmonary vasodilators (r = 0.42, P = 0.02).</div></div><div><h3>Conclusions</h3><div>The PVR response to NO testing associated with short-term efficacy of pulmonary vasodilators in patients with severe LD-PH. Prospective studies of PVR response to NO testing on the clinical efficacy in large-scale LD-PH cohorts are warranted.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 326-333"},"PeriodicalIF":2.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562220","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":"Successful treatment by switching from benralizumab to dupilumab in a patient with allergic bronchopulmonary mycosis caused by Schizophyllum commune","authors":"Takumi Motohashi , Muneyuki Sekiya , Susumu Sakamoto , Kohshi Fukuda , Yasuhiko Nakamura , Masakazu Sasaki , Naobumi Tochigi , Takashi Yaguchi , Katsuhiko Kamei , Kazuma Kishi","doi":"10.1016/j.resinv.2025.02.011","DOIUrl":"10.1016/j.resinv.2025.02.011","url":null,"abstract":"<div><div>A 79-year-old female patient with a history of bronchial asthma was diagnosed with allergic bronchopulmonary aspergillosis. Her symptoms temporarily improved with inhaled corticosteroid/long-acting β2-agonist therapy. However, 10 months after treatment, her asthma symptoms worsened. Sputum culture showed white cotton wool colonies, which were identified as <em>Schizophyllum commune</em> via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and gene sequencing. The patient tested positive for <em>S. commune</em>-specific IgG. Thus, she was diagnosed with <em>Schizophyllum commune</em>-induced allergic bronchopulmonary mycosis<em>.</em> The patient was initially treated with benralizumab. However, it was not effective. After switching to dupilumab, her symptoms and mucus plugs improved.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 311-313"},"PeriodicalIF":2.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562317","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":"Analysis of risk factors for long COVID after mild COVID-19 during the Omicron wave in Japan","authors":"Hotaka Namie , Takahiro Takazono , Rina Kawasaki , Hiroshi Yano , Yuya Ito , Nana Nakada , Tatsuro Hirayama , Masataka Yoshida , Kazuaki Takeda , Shotaro Ide , Shinnosuke Takemoto , Naoki Iwanaga , Masato Tashiro , Naoki Hosogaya , Hiroshi Ishimoto , Noriho Sakamoto , Yasushi Obase , Toyomitsu Sawai , Kohji Hashiguchi , Yuichi Fukuda , Koichi Izumikawa","doi":"10.1016/j.resinv.2025.02.008","DOIUrl":"10.1016/j.resinv.2025.02.008","url":null,"abstract":"<div><h3>Background</h3><div>Post-COVID-19 syndrome, referred to as “long COVID,” is characterized by persistent symptoms that develop during or after SRAS-CoV-2 infection lasting for ≥12 weeks, which cannot be explained by factors other than COVID-19. Previous studies before the Omicron pandemic have identified female sex, older age (≥50 years), severity of illness, obesity, diabetes, and smoking as risk factors for long COVID. However, data on long COVID following the emergence of the Omicron variants are limited.</div></div><div><h3>Methods</h3><div>An online survey was conducted among outpatients diagnosed with mild COVID-19 at 14 participating institutions in Japan between July 30, 2022, and December 31, 2023.</div></div><div><h3>Results</h3><div>Of the included 246 cases, 76 (35.5%) experienced at least one long COVID symptom 12 weeks after onset. Logistic regression analysis revealed that age ≥40 years was significantly associated with an increased risk of respiratory (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.67–8.65) and neurologic symptoms (OR: 4.53, 95% CI: 1.84–11.13). Conversely, antiviral drug use was associated with a decreased risk of respiratory symptoms (OR: 0.31, 95% CI: 0.11–0.93).</div></div><div><h3>Conclusion</h3><div>Caution is warranted when treating patients over 40 years of age with mild COVID-19 due to their higher susceptibility to developing long COVID. Antiviral drugs may be beneficial in managing respiratory symptoms and mitigating disease severity.</div></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":"63 3","pages":"Pages 303-310"},"PeriodicalIF":2.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550000","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}