Bronchopulmonary dysplasia (BPD) is a chronic lung condition primarily affecting premature infants. It significantly impacts their growth, development, and health. Recently, in vitro models have been created, offering new insights into the causes and potential treatments for BPD. This review summarizes the current methods for creating in vitro models of BPD. It also discusses their evaluation criteria and applications in drug testing and biological research. This paper evaluates the advantages and disadvantages of different models.
{"title":"Establishment and Evaluation of Cell Models for Bronchopulmonary Dysplasia: Challenges and Prospects","authors":"Zhenzhuang Zou, Li Fu, Jiaying Liu, Bo Huang","doi":"10.1111/crj.70118","DOIUrl":"https://doi.org/10.1111/crj.70118","url":null,"abstract":"<p>Bronchopulmonary dysplasia (BPD) is a chronic lung condition primarily affecting premature infants. It significantly impacts their growth, development, and health. Recently, in vitro models have been created, offering new insights into the causes and potential treatments for BPD. This review summarizes the current methods for creating in vitro models of BPD. It also discusses their evaluation criteria and applications in drug testing and biological research. This paper evaluates the advantages and disadvantages of different models.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Interleukin-15 (IL-15) is a pleiotropic cytokine recognized as a promising therapeutic agent in cancer immunotherapy. IL-15 superagonists have shown efficacy across various cancers, yet their effects in lung cancer immunotherapy remain underexplored.
Methods
This study evaluated the antitumor effects of SHR-1501 through intratumoral injection in two murine lung cancer models: Lewis lung carcinoma (LLC) and Kras G12D/p53−/− (KP). We employed flow cytometry to assess immune cell populations in the tumor microenvironment (TME) and systemic circulation. Immunohistochemistry (IHC) was used to analyze TME changes in tumor tissues, while single-cell RNA sequencing provided insights into TME modulation following SHR-1501 treatment. Additionally, we assessed the synergistic potential of combining SHR-1501 with PD-1 monoclonal antibody (mAb) therapy and explored the abscopal effect of SHR-1501.
Results
SHR-1501 significantly inhibited tumor growth in both KP and LLC models at 5 μg and 15 μg doses (p = 0.0022 and p = 0.0002, respectively, for KP; p = 0.0508 and p = 0.0131, respectively, for LLC). Flow cytometry revealed increased infiltration of CD8+ T cells, effector memory CD8+ T cells (TEM), and natural killer (NK) cells in the TME. SHR-1501 also enhanced systemic immune responses, increasing CD8+ T cells and TEM populations in peripheral blood and spleen, with an early NK cell elevation on day 7 post-treatment. Single-cell analysis indicated that SHR-1501 promoted the activity of macrophages, increasing M1 macrophage proportions. Moreover, SHR-1501 enhanced the antitumor immune response by promoting pro-inflammatory changes across multiple cell types within the TME, including neutrophils, fibroblasts, and endothelial cells. When combined with PD-1mAb, SHR-1501 exhibited potent synergistic antitumor effects. The combination therapy significantly prolonged overall survival with no significant toxicity observed. Furthermore, SHR-1501 may have the ability to induce an abscopal effect.
Conclusion
SHR-1501 demonstrated potent antitumor activity, especially when combined with PD-1 mAb. Its mechanism likely involves promoting CD8+ T cell and NK cell infiltration and enhancing M1 macrophage activity. These findings provide evidence for further clinical trials exploring SHR-1501 in nonsmall cell lung cancer (NSCLC) therapy.
{"title":"IL-15 Superagonist SHR-1501 Enhances Immune Responses in Lung Cancer by Modulating Tumor Microenvironment","authors":"Qian Zhang, Congli Hu, Minlin Jiang, Yuanyuan Wang, Heng Luo, Xuefei Li","doi":"10.1111/crj.70117","DOIUrl":"https://doi.org/10.1111/crj.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Interleukin-15 (IL-15) is a pleiotropic cytokine recognized as a promising therapeutic agent in cancer immunotherapy. IL-15 superagonists have shown efficacy across various cancers, yet their effects in lung cancer immunotherapy remain underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study evaluated the antitumor effects of SHR-1501 through intratumoral injection in two murine lung cancer models: Lewis lung carcinoma (LLC) and Kras G12D/p53−/− (KP). We employed flow cytometry to assess immune cell populations in the tumor microenvironment (TME) and systemic circulation. Immunohistochemistry (IHC) was used to analyze TME changes in tumor tissues, while single-cell RNA sequencing provided insights into TME modulation following SHR-1501 treatment. Additionally, we assessed the synergistic potential of combining SHR-1501 with PD-1 monoclonal antibody (mAb) therapy and explored the abscopal effect of SHR-1501.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SHR-1501 significantly inhibited tumor growth in both KP and LLC models at 5 μg and 15 μg doses (<i>p</i> = 0.0022 and <i>p</i> = 0.0002, respectively, for KP; <i>p</i> = 0.0508 and <i>p</i> = 0.0131, respectively, for LLC). Flow cytometry revealed increased infiltration of CD8+ T cells, effector memory CD8+ T cells (TEM), and natural killer (NK) cells in the TME. SHR-1501 also enhanced systemic immune responses, increasing CD8+ T cells and TEM populations in peripheral blood and spleen, with an early NK cell elevation on day 7 post-treatment. Single-cell analysis indicated that SHR-1501 promoted the activity of macrophages, increasing M1 macrophage proportions. Moreover, SHR-1501 enhanced the antitumor immune response by promoting pro-inflammatory changes across multiple cell types within the TME, including neutrophils, fibroblasts, and endothelial cells. When combined with PD-1mAb, SHR-1501 exhibited potent synergistic antitumor effects. The combination therapy significantly prolonged overall survival with no significant toxicity observed. Furthermore, SHR-1501 may have the ability to induce an abscopal effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SHR-1501 demonstrated potent antitumor activity, especially when combined with PD-1 mAb. Its mechanism likely involves promoting CD8+ T cell and NK cell infiltration and enhancing M1 macrophage activity. These findings provide evidence for further clinical trials exploring SHR-1501 in nonsmall cell lung cancer (NSCLC) therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate the early effect of esketamine on the tumor metastatic microenvironment in patients with lung cancer.
Methods
Sixteen adults aged 45–80 years with the American Society of Anesthesiologists (ASA) 1 to 3 were randomly divided into the experimental group (group E) and the control group (group C). Group E received esketamine at 1 mg/kg during anesthesia induction and a continuous infusion of 0.5 mg/kg/h during the surgery. Group C was given the same amount of normal saline infusion. Patient-controlled intravenous analgesia (PCIA) in group E was administered using dexmedetomidine (0.5 mg/kg) + esketamine (50 mg) + dexamethasone (5 mg). PCIA in group C was the same dose of dexmedetomidine and dexamethasone. Data were recorded at 14 points from admission to the third day after surgery (T0–14). Parameters recorded included hemodynamics, wake time, remifentanil dosage, and so on. At T0, T10, T13, and T14, TNF-α, IL-2, IL-10, MMP-9, and VEGF-C were measured.
Results
Compared with T0, the differences of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor-C (VEGF-C) in the two groups were statistically significant (p < 0.05). When compared to group C, VEGF-C in group E was reduced at T10 and T13 (p < 0.05). For both groups, there were intragroup differences in the changes of MMP-9 and VEGF-C levels (p < 0.05). Compared to group C, on the postoperative, group E exhibited a lower change rate of TNF-α and VEGF-C (p < 0.05).
Conclusion
Perioperative application of esketamine in patients with lung cancer provided significant sedative and analgesic effects and affected cytokines in the tumor microenvironment.
{"title":"The Early Effects of Esketamine on the Tumor Metastatic Microenvironment in Postoperative Lung Cancer Patients","authors":"Yong Wang, Weijing Li, Li Jia, Junmei Shen, Chao Li, Huiqun Jia","doi":"10.1111/crj.70108","DOIUrl":"https://doi.org/10.1111/crj.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To investigate the early effect of esketamine on the tumor metastatic microenvironment in patients with lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixteen adults aged 45–80 years with the American Society of Anesthesiologists (ASA) 1 to 3 were randomly divided into the experimental group (group E) and the control group (group C). Group E received esketamine at 1 mg/kg during anesthesia induction and a continuous infusion of 0.5 mg/kg/h during the surgery. Group C was given the same amount of normal saline infusion. Patient-controlled intravenous analgesia (PCIA) in group E was administered using dexmedetomidine (0.5 mg/kg) + esketamine (50 mg) + dexamethasone (5 mg). PCIA in group C was the same dose of dexmedetomidine and dexamethasone. Data were recorded at 14 points from admission to the third day after surgery (T<sub>0–14</sub>). Parameters recorded included hemodynamics, wake time, remifentanil dosage, and so on. At T<sub>0</sub>, T<sub>10</sub>, T<sub>13</sub>, and T<sub>14</sub>, TNF-α, IL-2, IL-10, MMP-9, and VEGF-C were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with T<sub>0</sub>, the differences of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor-C (VEGF-C) in the two groups were statistically significant (<i>p</i> < 0.05). When compared to group C, VEGF-C in group E was reduced at T<sub>10</sub> and T<sub>13</sub> (<i>p</i> < 0.05). For both groups, there were intragroup differences in the changes of MMP-9 and VEGF-C levels (<i>p</i> < 0.05). Compared to group C, on the postoperative, group E exhibited a lower change rate of TNF-α and VEGF-C (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Perioperative application of esketamine in patients with lung cancer provided significant sedative and analgesic effects and affected cytokines in the tumor microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Zarei, Abbas Shamsalinia, Asiyeh Yari, Pooyan Afzali Hasirini, Ali Khani Jeihooni
Background
Using smoking and hookah has increased among high school students in recent years. Therefore, the present study aimed to determine the effect of educational intervention based on the theory of planned behaviour (TPB) on reducing smoking and hookah use among high school students.
Methods
This experimental study was conducted on 300 high school male students in Fasa City, Fars Province, Iran, in 2021–2022. Subjects were selected using a simple sampling method and were randomly divided into intervention (n = 150) and control (n = 150) groups. The educational intervention for the experimental group included 7 sessions of 45–55 min using small group discussion, question and answer, practical demonstrations, video clips, PowerPoint, and booklets. Before the intervention and 3 months after the educational intervention, both experimental and control groups completed the questionnaire. Data were analyzed using SPSS 22 software through Chi-square, independent t-test, paired t-test, and McNemar test.
Results
The mean age of the experimental and control groups was 17.89 + 1.46 and 17.1 + 1.58 years. The results showed that before the educational intervention, there was no significant difference between the experimental and control groups in terms of awareness, attitude, subjective norms, perceived behavioral control, and behavioral intention; however, 4 months after the educational intervention, there was a significant increase in the experimental group. Also, before the educational intervention, there was no significant difference between the two groups in terms of current smoking and hookah use; however, 4 months after the intervention, there was a significant difference between the two groups.
Conclusion
Implementing the TPB-directed instructional sessions resulted in reducing smoking and hookah use among high school students.
{"title":"Effect of Educational Intervention Based on Theory of Planned Behavior on Reducing Smoking and Hookah Use Among High School Male Students","authors":"Ali Zarei, Abbas Shamsalinia, Asiyeh Yari, Pooyan Afzali Hasirini, Ali Khani Jeihooni","doi":"10.1111/crj.70119","DOIUrl":"https://doi.org/10.1111/crj.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Using smoking and hookah has increased among high school students in recent years. Therefore, the present study aimed to determine the effect of educational intervention based on the theory of planned behaviour (TPB) on reducing smoking and hookah use among high school students.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This experimental study was conducted on 300 high school male students in Fasa City, Fars Province, Iran, in 2021–2022. Subjects were selected using a simple sampling method and were randomly divided into intervention (<i>n</i> = 150) and control (<i>n</i> = 150) groups. The educational intervention for the experimental group included 7 sessions of 45–55 min using small group discussion, question and answer, practical demonstrations, video clips, PowerPoint, and booklets. Before the intervention and 3 months after the educational intervention, both experimental and control groups completed the questionnaire. Data were analyzed using SPSS 22 software through Chi-square, independent <i>t</i>-test, paired <i>t</i>-test, and McNemar test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of the experimental and control groups was 17.89 + 1.46 and 17.1 + 1.58 years. The results showed that before the educational intervention, there was no significant difference between the experimental and control groups in terms of awareness, attitude, subjective norms, perceived behavioral control, and behavioral intention; however, 4 months after the educational intervention, there was a significant increase in the experimental group. Also, before the educational intervention, there was no significant difference between the two groups in terms of current smoking and hookah use; however, 4 months after the intervention, there was a significant difference between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Implementing the TPB-directed instructional sessions resulted in reducing smoking and hookah use among high school students.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuberculosis (TB) treatment is challenged by a long duration, poor adherence, and the high risk of drug-induced liver injury (DILI). T-cell immunity is essential for anti-mycobacterial defense, but current immune-monitoring methods poorly reflect disease severity and treatment response. Correlations of immune subpopulations with TB severity, DILI, and treatment prognosis remain poorly understood.
Methods
Peripheral blood mononuclear cells were collected from confirmed TB patients (n = 40). Multiparameter flow cytometry analysis was used to assess previously defined TB-associated T-cell phenotypes based on the co-expression of cytokines and immune checkpoint molecules following stimulation with two Mycobacterium tuberculosis peptides: culture filtrate protein 10 and early secreted antigenic target 6. Patients were subgrouped by disease severity, DILI, and treatment regimen (16-week short course vs. 24-week standard).
Results
Specific subsets (14/124) were found to be associated with disease severity. Notably, six of 14 subsets were positive for programmed death-ligand 1 (PD-L1), indicating its potential role in disease progression. DILI was associated with three interleukin (IL)-21+ subsets (naïve CD4+, memory CD8+, and interferon [IFN]-γ− CD4+ T cells) and IL-17+ memory CD8+ T cells, along with PD-L1+TIM-3+CD4+ T cells (all p < 0.05). The 16-week and 24-week treatment groups showed a significant difference in IFN-γ+ naïve CD8+ T cells at week 16 (p = 0.013), but not at treatment completion (p = 0.393), despite the different durations.
Conclusions
This study identifies specific T-cell phenotypes associated with TB severity, DILI, and treatment dynamics, highlighting potential immune markers for disease monitoring and DILI prediction.
{"title":"Association of T-Cell Profiles With Disease Severity, Drug-Induced Liver Injury, and Treatment Completion in Tuberculosis","authors":"Yifan He, Xubin Zheng, Zihan Dang, Xiaohui Hao, Yidian Liu, Peng Wang, Yingying Chen, Ying Wang, Wei Sha","doi":"10.1111/crj.70114","DOIUrl":"https://doi.org/10.1111/crj.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tuberculosis (TB) treatment is challenged by a long duration, poor adherence, and the high risk of drug-induced liver injury (DILI). T-cell immunity is essential for anti-mycobacterial defense, but current immune-monitoring methods poorly reflect disease severity and treatment response. Correlations of immune subpopulations with TB severity, DILI, and treatment prognosis remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were collected from confirmed TB patients (<i>n</i> = 40). Multiparameter flow cytometry analysis was used to assess previously defined TB-associated T-cell phenotypes based on the co-expression of cytokines and immune checkpoint molecules following stimulation with two <i>Mycobacterium tuberculosis</i> peptides: culture filtrate protein 10 and early secreted antigenic target 6. Patients were subgrouped by disease severity, DILI, and treatment regimen (16-week short course vs. 24-week standard).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Specific subsets (14/124) were found to be associated with disease severity. Notably, six of 14 subsets were positive for programmed death-ligand 1 (PD-L1), indicating its potential role in disease progression. DILI was associated with three interleukin (IL)-21<sup>+</sup> subsets (naïve CD4<sup>+</sup>, memory CD8<sup>+</sup>, and interferon [IFN]-γ<sup>−</sup> CD4<sup>+</sup> T cells) and IL-17<sup>+</sup> memory CD8<sup>+</sup> T cells, along with PD-L1<sup>+</sup>TIM-3<sup>+</sup>CD4<sup>+</sup> T cells (all <i>p</i> < 0.05). The 16-week and 24-week treatment groups showed a significant difference in IFN-γ<sup>+</sup> naïve CD8<sup>+</sup> T cells at week 16 (<i>p</i> = 0.013), but not at treatment completion (<i>p</i> = 0.393), despite the different durations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identifies specific T-cell phenotypes associated with TB severity, DILI, and treatment dynamics, highlighting potential immune markers for disease monitoring and DILI prediction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agata Anna Lewandowska, Dorota Waśniowska, Cezary Rybacki, Michał Graczyk, Ola Duszyńska, Helena Mirus-Arabik, Aleksandra Gaczkowska, Małgorzata Kołodziej
Interstitial lung disease (ILD) associated with connective tissue disease (CTD) is a challenging entity burdened with multiple risk factors and undesirable events. ILD can occur at any time and progress regardless of the underlying disease activity. Apart from the established difficulties in choosing an appropriate treatment strategy for both pulmonary and extrapulmonary involvement, such patients require a holistic and multidisciplinary approach. In an attempt to emphasize the significance of the problem and suggest potential research directions, the authors present four potentially most important and often misdiagnosed complications of the CTD-associated ILD, in the form of acute exacerbation, drug-induced pulmonary toxicity, nonspecific infection, and tuberculosis. Similar clinical manifestations of the patient's progressive deterioration, as well as the complex etiology of pulmonary involvement, raise controversies and force difficult therapeutic decisions. High morbidity and mortality among patients with progressive CTD-associated ILDs necessitate further research in an attempt to enhance the treatment management in each CTD and improve the patients' quality of life.
{"title":"Pulmonary Complications in Connective Tissue Disease-Associated Interstitial Lung Disease.","authors":"Agata Anna Lewandowska, Dorota Waśniowska, Cezary Rybacki, Michał Graczyk, Ola Duszyńska, Helena Mirus-Arabik, Aleksandra Gaczkowska, Małgorzata Kołodziej","doi":"10.1111/crj.70116","DOIUrl":"10.1111/crj.70116","url":null,"abstract":"<p><p>Interstitial lung disease (ILD) associated with connective tissue disease (CTD) is a challenging entity burdened with multiple risk factors and undesirable events. ILD can occur at any time and progress regardless of the underlying disease activity. Apart from the established difficulties in choosing an appropriate treatment strategy for both pulmonary and extrapulmonary involvement, such patients require a holistic and multidisciplinary approach. In an attempt to emphasize the significance of the problem and suggest potential research directions, the authors present four potentially most important and often misdiagnosed complications of the CTD-associated ILD, in the form of acute exacerbation, drug-induced pulmonary toxicity, nonspecific infection, and tuberculosis. Similar clinical manifestations of the patient's progressive deterioration, as well as the complex etiology of pulmonary involvement, raise controversies and force difficult therapeutic decisions. High morbidity and mortality among patients with progressive CTD-associated ILDs necessitate further research in an attempt to enhance the treatment management in each CTD and improve the patients' quality of life.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 8","pages":"e70116"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wang Chun Kwok, Mary Sau Man Ip, Terence Chi Chun Tam, James Chung Man Ho, David Chi Leung Lam, Kwan Ling Julie Wang
Background
Fractional exhaled nitric oxide (FENO) serves as a marker of eosinophil-mediated airway inflammation and has been used in asthma diagnosis, phenotyping, and guidance regarding selection and adjustment of asthma therapy. Studies suggested that FENO correlated with asthma symptoms, peripheral blood eosinophil level, blood IgE level, and spirometry indicators of airway obstruction. However, the results are inconsistent across studies.
Methods
A prospective cross-sectional study was conducted in Queen Mary Hospital among adult patients with severe asthma. Patients had spirometry with bronchodilator reversibility and same-day FENO. Asthma control test (ACT) score and blood eosinophil and total IgE levels were measured within 4 weeks of FENO and spirometry. The primary outcome was the correlation of FENO and spirometric values. The secondary outcomes included the correlation of FENO with ACT score, blood eosinophil, and total IgE levels.
Results
One hundred thirty-five severe asthma patients with FENO performed were included in the study. FENO was negatively correlated with pre-bronchodilator FEV1 (L) (r = −0.188, p = 0.029), pre-bronchodilator FEV1 (% predicted) (r = −0.169, p = 0.050), pre-bronchodilator FEV1/FVC ratio (r = −0.269, p = 0.002), and post-bronchodilator FEV1/FVC (r = −0.215, p = 0.018). FENO was positively correlated with bronchodilator reversibility (mL) (r = 0.248, p = 0.006) and bronchodilator reversibility (%) (r = 0.823, p = 0.002), baseline blood eosinophil level by absolute cell count (r = 0.308, p < 0.001) and by percentage (r = 0.361, p < 0.001).
Conclusion
In adult patients with severe asthma, FENO might have a negative correlation with the FEV1, FEV1/FVC ratio, and a positive correlation with bronchodilator reversibility, as well as with blood eosinophil levels.
呼气一氧化氮分数（FENO）是嗜酸性粒细胞介导的气道炎症的标志物，已被用于哮喘诊断、表型分析和指导哮喘治疗的选择和调整。研究表明，FENO与哮喘症状、外周血嗜酸性粒细胞水平、血IgE水平、气道阻塞肺活量测定指标相关。然而，不同研究的结果并不一致。方法在玛丽医院对成年重症哮喘患者进行前瞻性横断面研究。患者进行肺活量测定，支气管扩张剂可逆性和当日FENO。哮喘控制试验（ACT）评分、血嗜酸性粒细胞和总IgE水平在FENO和肺活量测定4周内测定。主要终点是FENO与肺活量测定值的相关性。次要结果包括FENO与ACT评分、血嗜酸性粒细胞和总IgE水平的相关性。结果共纳入135例经FENO治疗的重症哮喘患者。FENO与支气管扩张剂前FEV1 (L) （r = - 0.188, p = 0.029）、支气管扩张剂前FEV1（预测%）（r = - 0.169, p = 0.050）、支气管扩张剂前FEV1/FVC比值（r = - 0.269, p = 0.002）、支气管扩张剂后FEV1/FVC （r = - 0.215, p = 0.018）负相关。FENO与支气管扩张剂可逆性（mL） （r = 0.248, p = 0.006）、支气管扩张剂可逆性（%）（r = 0.823, p = 0.002）、基线血嗜酸性粒细胞绝对计数（r = 0.308, p < 0.001）和百分比（r = 0.361, p < 0.001）呈正相关。结论成人重症哮喘患者FENO可能与FEV1、FEV1/FVC比值呈负相关，与支气管扩张剂可逆性、血嗜酸性粒细胞水平呈正相关。
{"title":"Correlation of FENO With Spirometric Measurements and Blood Eosinophil Level in Patients With Severe Asthma","authors":"Wang Chun Kwok, Mary Sau Man Ip, Terence Chi Chun Tam, James Chung Man Ho, David Chi Leung Lam, Kwan Ling Julie Wang","doi":"10.1111/crj.70094","DOIUrl":"https://doi.org/10.1111/crj.70094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fractional exhaled nitric oxide (FE<sub>NO</sub>) serves as a marker of eosinophil-mediated airway inflammation and has been used in asthma diagnosis, phenotyping, and guidance regarding selection and adjustment of asthma therapy. Studies suggested that FE<sub>NO</sub> correlated with asthma symptoms, peripheral blood eosinophil level, blood IgE level, and spirometry indicators of airway obstruction. However, the results are inconsistent across studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective cross-sectional study was conducted in Queen Mary Hospital among adult patients with severe asthma. Patients had spirometry with bronchodilator reversibility and same-day FE<sub>NO</sub>. Asthma control test (ACT) score and blood eosinophil and total IgE levels were measured within 4 weeks of FE<sub>NO</sub> and spirometry. The primary outcome was the correlation of FE<sub>NO</sub> and spirometric values. The secondary outcomes included the correlation of FE<sub>NO</sub> with ACT score, blood eosinophil, and total IgE levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred thirty-five severe asthma patients with FE<sub>NO</sub> performed were included in the study. FE<sub>NO</sub> was negatively correlated with pre-bronchodilator FEV<sub>1</sub> (L) (<i>r</i> = −0.188, <i>p</i> = 0.029), pre-bronchodilator FEV<sub>1</sub> (% predicted) (<i>r</i> = −0.169, <i>p</i> = 0.050), pre-bronchodilator FEV1/FVC ratio (<i>r</i> = −0.269, <i>p</i> = 0.002), and post-bronchodilator FEV<sub>1</sub>/FVC (<i>r</i> = −0.215, <i>p</i> = 0.018). FE<sub>NO</sub> was positively correlated with bronchodilator reversibility (mL) (<i>r</i> = 0.248, <i>p</i> = 0.006) and bronchodilator reversibility (%) (<i>r</i> = 0.823, <i>p</i> = 0.002)<i>,</i> baseline blood eosinophil level by absolute cell count (<i>r</i> = 0.308, <i>p</i> < 0.001) and by percentage (<i>r</i> = 0.361, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In adult patients with severe asthma, FE<sub>NO</sub> might have a negative correlation with the FEV<sub>1</sub>, FEV<sub>1</sub>/FVC ratio, and a positive correlation with bronchodilator reversibility, as well as with blood eosinophil levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study is to investigate the genetic susceptibility and risk factors of EGF gene rs1897990 and rs1524106 in lung adenocarcinoma young patients aged ≤ 45 years.
Methods
A case–control study was conducted. DNA was extracted and identified from 88 samples from case and control groups by single-nucleotide polymorphism assay. PCR amplification was performed by TaqMan probe method, and the factors of smoking, drinking, sex, and age were also included. To investigate the clinical factors and genotyping differences between case and control groups.
Results
Smoking was an influential factor in young lung adenocarcinoma patients. The mutation frequency of EGF gene rs1897990 CT heterozygous mutant was different between the two groups (p = 0.021). The T alleles of EGF rs1897990 and rs1524106 were significantly different between the two groups (p = 0.034 and p = 0.023).
Conclusions
The young lung adenocarcinoma population (≤ 45 years old) is susceptible to EGF rs1897990 and rs1524106 variants, with smoking being another risk factor. Additionally, smoking may enhance the risk of EGF rs1897990 and rs1524106 variants threatening the development of lung adenocarcinoma.
{"title":"Molecular Marker Discovery and Evaluation: EGF rs1897990 and rs1524106 Variants in a China Lung Adenocarcinoma Young Population","authors":"Huiwen Pan, Xiangyang Wang, Lijie Zheng, Jinye Wang, Guowen Ding, Jingfeng Zhu, Zhijie Fang","doi":"10.1111/crj.70113","DOIUrl":"https://doi.org/10.1111/crj.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study is to investigate the genetic susceptibility and risk factors of <i>EGF</i> gene rs1897990 and rs1524106 in lung adenocarcinoma young patients aged ≤ 45 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A case–control study was conducted. DNA was extracted and identified from 88 samples from case and control groups by single-nucleotide polymorphism assay. PCR amplification was performed by TaqMan probe method, and the factors of smoking, drinking, sex, and age were also included. To investigate the clinical factors and genotyping differences between case and control groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Smoking was an influential factor in young lung adenocarcinoma patients. The mutation frequency of <i>EGF</i> gene rs1897990 CT heterozygous mutant was different between the two groups (<i>p</i> = 0.021). The T alleles of <i>EGF</i> rs1897990 and rs1524106 were significantly different between the two groups (<i>p</i> = 0.034 and <i>p</i> = 0.023).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The young lung adenocarcinoma population (≤ 45 years old) is susceptible to <i>EGF</i> rs1897990 and rs1524106 variants, with smoking being another risk factor. Additionally, smoking may enhance the risk of <i>EGF</i> rs1897990 and rs1524106 variants threatening the development of lung adenocarcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disease caused by sensitivity to Aspergillus fumigatus. Diffuse lung lesions as a radiological presentation of ABPA are exceedingly rare, with no documented case in the literature. We present a case with asthma. High-resolution computed tomography (HRCT) of the chest revealed diffuse lung lesions. Additionally, arterial blood gas analysis revealed life-threatening acute Type II respiratory failure. Initially, there was suspicion of a mycobacterial infection. However, a subsequent diagnosis revealed the atypical presentation of ABPA. Finally, the patient's symptoms improved, and lung shadows were absorbed after undergoing mechanical ventilation with tracheal intubation and receiving methylprednisolone treatment.
{"title":"Acute Respiratory Failure in Allergic Bronchopulmonary Aspergillosis Characterized by Diffuse Lung Lesions: A Case Report and Literature Review","authors":"Hongmei Ren","doi":"10.1111/crj.70115","DOIUrl":"https://doi.org/10.1111/crj.70115","url":null,"abstract":"<p>Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disease caused by sensitivity to <i>Aspergillus fumigatus</i>. Diffuse lung lesions as a radiological presentation of ABPA are exceedingly rare, with no documented case in the literature. We present a case with asthma. High-resolution computed tomography (HRCT) of the chest revealed diffuse lung lesions. Additionally, arterial blood gas analysis revealed life-threatening acute Type II respiratory failure. Initially, there was suspicion of a mycobacterial infection. However, a subsequent diagnosis revealed the atypical presentation of ABPA. Finally, the patient's symptoms improved, and lung shadows were absorbed after undergoing mechanical ventilation with tracheal intubation and receiving methylprednisolone treatment.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengting Sun, Yuqing Ni, Xueling Wu, Hao Tian, Yijun Song, Yinzhou Feng, Yunxin Guo, Yong Zhang, Jun Yin, Charles A. Powell, Chunxue Bai, Yuanlin Song, Dawei Yang
Introduction
The current clinical management of pulmonary nodules relies heavily on CT follow-up, without early intervention. This retrospective study investigated the efficacy of OM-85, a standardized lysate of human respiratory bacteria, in the treatment of high-risk pulmonary nodules detected by computed tomography (CT) in patients with chronic bronchitis.
Methods
This study included 72 patients (93 enrolled nodules) who underwent treatment with OM-85 and a matched control group of 90 patients (111 control nodules). The primary endpoint included reduced size of high-risk ground glass nodules based on thin-layer CT scans during follow-up. Flow cytometry, multiplex immunofluorescence (mIF) analysis, and scRNA-seq data were employed to determine differences in the immune cell subsets between the treatment and control groups.
Results
Oral OM-85 treatment significantly reduced lung nodule diameter (p = 0.031), the risk probability of malignancy (p = 0.003), and the likelihood of clinical disease progression (p = 0.0091). The effects of OM-85 treatment were more pronounced in older patients (> 65-year-old) (p = 0.029) and those with longer follow-up cycles (> 200 days) (p = 0.011). The peripheral blood samples showed a significantly higher proportion of natural killer (NK) cells in the treatment group. Furthermore, mIF staining of the pulmonary nodules and scRNA-seq data demonstrated a higher percentage of NK cells in the treatment group compared with the control group (p = 0.0003).
Conclusion
OM-85 reduced the size of high-risk pulmonary nodules and decreased the risk of malignant probability and disease progression in patients with chronic bronchitis by increasing the proportion of NK cells. Therefore, OM-85 is a potential drug for the treatment of high-risk pulmonary nodules in patients with chronic bronchitis.
{"title":"OM-85, a Bacterial Lysate, Reduces Pulmonary Nodule Malignant Probability: A Retrospective Study","authors":"Mengting Sun, Yuqing Ni, Xueling Wu, Hao Tian, Yijun Song, Yinzhou Feng, Yunxin Guo, Yong Zhang, Jun Yin, Charles A. Powell, Chunxue Bai, Yuanlin Song, Dawei Yang","doi":"10.1111/crj.70109","DOIUrl":"https://doi.org/10.1111/crj.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The current clinical management of pulmonary nodules relies heavily on CT follow-up, without early intervention. This retrospective study investigated the efficacy of OM-85, a standardized lysate of human respiratory bacteria, in the treatment of high-risk pulmonary nodules detected by computed tomography (CT) in patients with chronic bronchitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 72 patients (93 enrolled nodules) who underwent treatment with OM-85 and a matched control group of 90 patients (111 control nodules). The primary endpoint included reduced size of high-risk ground glass nodules based on thin-layer CT scans during follow-up. Flow cytometry, multiplex immunofluorescence (mIF) analysis, and scRNA-seq data were employed to determine differences in the immune cell subsets between the treatment and control groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Oral OM-85 treatment significantly reduced lung nodule diameter (<i>p</i> = 0.031), the risk probability of malignancy (<i>p</i> = 0.003), and the likelihood of clinical disease progression (<i>p</i> = 0.0091). The effects of OM-85 treatment were more pronounced in older patients (> 65-year-old) (<i>p</i> = 0.029) and those with longer follow-up cycles (> 200 days) (<i>p</i> = 0.011). The peripheral blood samples showed a significantly higher proportion of natural killer (NK) cells in the treatment group. Furthermore, mIF staining of the pulmonary nodules and scRNA-seq data demonstrated a higher percentage of NK cells in the treatment group compared with the control group (<i>p</i> = 0.0003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>OM-85 reduced the size of high-risk pulmonary nodules and decreased the risk of malignant probability and disease progression in patients with chronic bronchitis by increasing the proportion of NK cells. Therefore, OM-85 is a potential drug for the treatment of high-risk pulmonary nodules in patients with chronic bronchitis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"19 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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