Pub Date : 2024-06-13DOI: 10.1183/23120541.00345-2024
E. King, J. McClendon, Thienthanh Trinh, Jennifer L. Matsuda, Katelyn H. Lyn-Kew, A. Mccubbrey, K. Mould, P.M. Henson, W.J. Janssen
{"title":"Slamf7 is dispensable in mouse models of acute lung injury","authors":"E. King, J. McClendon, Thienthanh Trinh, Jennifer L. Matsuda, Katelyn H. Lyn-Kew, A. Mccubbrey, K. Mould, P.M. Henson, W.J. Janssen","doi":"10.1183/23120541.00345-2024","DOIUrl":"https://doi.org/10.1183/23120541.00345-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"22 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141346639","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 : 2024-06-13DOI: 10.1183/23120541.00235-2024
J. J. Herzig, Silvia Ulrich, S. Schneider, Julian Müller, M. Lichtblau, T. Ulrich, M. Bauer, M. Furian, K. Bloch, L. Mayer, E. I. Schwarz
Hypoxia is a trigger for sympathetic activation and autonomic cardiovascular dysfunction. Pulmonary vascular disease (PVD) is associated with hypoxemia, which increases with altitude. The aim was to investigate how exposure of patients with PVD to hypobaric hypoxia at altitude affects autonomic cardiovascular regulation.In a randomised cross-over study, patients with PVD were studied for one day and one night at an altitude of 2500 m (hypobaric hypoxia) and low altitude at 470 m in random order. Outcomes were heart rate variability (HRV) in the time domain and in the frequency domain (low/high frequency, LF/HF) and heart rate (HR) during day and night, and baroreflex sensitivity (BRS).In 25 patients with PVD (72% pulmonary arterial hypertension, 28% distal chronic thromboembolic pulmonary hypertension; mean±sdage 60.7±13.6 years), exposure to altitude resulted in significant increases in awake HR by 9.4 bpm (95%CI 6.3 to 12.4, p<0.001) and nocturnal HR by 9.0 bpm (95%CI 6.6 to 11.4, p<0.001) and significant changes in awake and particularly nocturnal HRV indicating decreasing parasympathetic and increasing sympathetic activity (change in daytime LF/HF 1.7 (95%CI 0.6 to 2.8), p=0.004; nocturnal LF/HF 1.9 (95%CI 0.3 to 3.4), p=0.022), and a significant decrease in BRS (−2.4 mmHg−1(95%CI - 4.3 to −0.4, p=0.024)).Exposure of PVD patients to altitude resulted in a significant change in HRV indicating an increase in sympathetic activity and a decrease in BRS. The relative change in HRV at altitude was more pronounced during sleep.
{"title":"Heart rate variability in pulmonary vascular disease at altitude: a randomised trial","authors":"J. J. Herzig, Silvia Ulrich, S. Schneider, Julian Müller, M. Lichtblau, T. Ulrich, M. Bauer, M. Furian, K. Bloch, L. Mayer, E. I. Schwarz","doi":"10.1183/23120541.00235-2024","DOIUrl":"https://doi.org/10.1183/23120541.00235-2024","url":null,"abstract":"Hypoxia is a trigger for sympathetic activation and autonomic cardiovascular dysfunction. Pulmonary vascular disease (PVD) is associated with hypoxemia, which increases with altitude. The aim was to investigate how exposure of patients with PVD to hypobaric hypoxia at altitude affects autonomic cardiovascular regulation.In a randomised cross-over study, patients with PVD were studied for one day and one night at an altitude of 2500 m (hypobaric hypoxia) and low altitude at 470 m in random order. Outcomes were heart rate variability (HRV) in the time domain and in the frequency domain (low/high frequency, LF/HF) and heart rate (HR) during day and night, and baroreflex sensitivity (BRS).In 25 patients with PVD (72% pulmonary arterial hypertension, 28% distal chronic thromboembolic pulmonary hypertension; mean±sdage 60.7±13.6 years), exposure to altitude resulted in significant increases in awake HR by 9.4 bpm (95%CI 6.3 to 12.4, p<0.001) and nocturnal HR by 9.0 bpm (95%CI 6.6 to 11.4, p<0.001) and significant changes in awake and particularly nocturnal HRV indicating decreasing parasympathetic and increasing sympathetic activity (change in daytime LF/HF 1.7 (95%CI 0.6 to 2.8), p=0.004; nocturnal LF/HF 1.9 (95%CI 0.3 to 3.4), p=0.022), and a significant decrease in BRS (−2.4 mmHg−1(95%CI - 4.3 to −0.4, p=0.024)).Exposure of PVD patients to altitude resulted in a significant change in HRV indicating an increase in sympathetic activity and a decrease in BRS. The relative change in HRV at altitude was more pronounced during sleep.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"61 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141346809","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 : 2024-06-13DOI: 10.1183/23120541.00203-2024
M. W. Betz, J. de Brandt, T. Aussieker, A. Monsegue, D. Houtvast, S. Gehlert, L. Verdijk, Luc J. C. van Loon, H. Gosker, Ramon Langen, Wim Derave, Chris Burtin, M. Spruit, T. Snijders
Chronic obstructive pulmonary disease (COPD) is a disease characterized by skeletal muscle dysfunction. A spatial relationship exists between satellite cells and muscle fiber capillaries, which has been suggested to be of major importance for satellite cell function. In the present study we compared the spatial relationship between satellite cells and capillaries in patients with COPD and age-matched healthy older adults.Muscle biopsies were obtained from thevastus lateralisof n=18 patients with COPD (8f/10 m, 66±5 y, mild to severe airflow obstruction) and n=18 age-, gender- and BMI-matched healthy control adults (8f/10 m, 68±5 y). Immunohistochemistry was used to assess type I/II muscle fiber size, distribution, myonuclear content, satellite cell number, and fiber capillarization. In addition, type I/II muscle fiber satellite cell distance to its nearest capillary was assessed.The percentage of type II muscle fibers was significantly greater in patients with COPD (62±10%) compared with control (50±12%, p<0.05). Muscle fiber capillarization was significantly lower in patients with COPD compared with controls (p<0.05). Whereas satellite cell content was not different between groups, type I and type II satellite cell distance to its nearest capillary was significantly greater in patients with COPD (type I: 21.3±4.8 and type II: 26.7±9.3 µm) compared with controls (type I: 16.1±3.5 and type II: 22.7±5.8 µm; p<0.05).Satellite cells are located at a greater distance from their nearest capillary in patients with COPD compared with age-matched controls. This increased distance could play a role in impaired satellite cell function in patients with COPD.
慢性阻塞性肺病（COPD）是一种以骨骼肌功能障碍为特征的疾病。卫星细胞和肌纤维毛细血管之间存在空间关系，这被认为对卫星细胞的功能至关重要。本研究中，我们比较了慢性阻塞性肺病患者和年龄匹配的健康老年人的卫星细胞与毛细血管之间的空间关系。免疫组化用于评估 I/II 型肌纤维的大小、分布、肌核含量、卫星细胞数量和纤维毛细血管化。与对照组（50±12%，P<0.05）相比，慢性阻塞性肺病患者的II型肌纤维比例明显增加（62±10%）。与对照组相比，慢性阻塞性肺病患者的肌纤维毛细血管化程度明显降低（P<0.05）。虽然卫星细胞含量在组间无差异，但与对照组（I 型：16.1±3.5 µm，II 型：22.7±5.8 µm；p<0.05）相比，慢性阻塞性肺病患者的 I 型和 II 型卫星细胞与其最近毛细血管的距离明显更大（I 型：21.3±4.8 µm，II 型：26.7±9.3 µm）。与年龄匹配的对照组相比，慢性阻塞性肺病患者的卫星细胞与最近的毛细血管的距离更远，这种距离的增加可能是慢性阻塞性肺病患者卫星细胞功能受损的原因之一。
{"title":"Muscle fiber satellite cells are located at a greater distance from capillaries in patients with COPD compared with healthy controls","authors":"M. W. Betz, J. de Brandt, T. Aussieker, A. Monsegue, D. Houtvast, S. Gehlert, L. Verdijk, Luc J. C. van Loon, H. Gosker, Ramon Langen, Wim Derave, Chris Burtin, M. Spruit, T. Snijders","doi":"10.1183/23120541.00203-2024","DOIUrl":"https://doi.org/10.1183/23120541.00203-2024","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a disease characterized by skeletal muscle dysfunction. A spatial relationship exists between satellite cells and muscle fiber capillaries, which has been suggested to be of major importance for satellite cell function. In the present study we compared the spatial relationship between satellite cells and capillaries in patients with COPD and age-matched healthy older adults.Muscle biopsies were obtained from thevastus lateralisof n=18 patients with COPD (8f/10 m, 66±5 y, mild to severe airflow obstruction) and n=18 age-, gender- and BMI-matched healthy control adults (8f/10 m, 68±5 y). Immunohistochemistry was used to assess type I/II muscle fiber size, distribution, myonuclear content, satellite cell number, and fiber capillarization. In addition, type I/II muscle fiber satellite cell distance to its nearest capillary was assessed.The percentage of type II muscle fibers was significantly greater in patients with COPD (62±10%) compared with control (50±12%, p<0.05). Muscle fiber capillarization was significantly lower in patients with COPD compared with controls (p<0.05). Whereas satellite cell content was not different between groups, type I and type II satellite cell distance to its nearest capillary was significantly greater in patients with COPD (type I: 21.3±4.8 and type II: 26.7±9.3 µm) compared with controls (type I: 16.1±3.5 and type II: 22.7±5.8 µm; p<0.05).Satellite cells are located at a greater distance from their nearest capillary in patients with COPD compared with age-matched controls. This increased distance could play a role in impaired satellite cell function in patients with COPD.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"58 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347018","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 : 2024-06-13DOI: 10.1183/23120541.00330-2024
A. Kantar, Woo-Jung Song, Andrew Bush, Grigorios Chatziparasidis
Non-cystic fibrosis bronchiectasis (NCFBE) belongs to the spectrum of chronic suppurative lung diseases and is characterised by persistent wet/sputum-productive cough and airway dilatation. Morphological and structural changes in the airways lead to changes in airflow, impair breathing-induced mucus transport and sliding, and reduce the shear forces of cough. Moreover, mucus hyperviscosity contributes to compromised ciliary activity and the pathogenesis of the disease. This review highlights the role of cough in NCFBE, especially with respect to mucus clearance.Cough is the principal backup mechanism when mucus clearance is impaired due to either or both reduced function of cilia- and breathing-induced mucus transport, as well as abnormal mucus. The efficiency of cough in overcoming the cohesive and adhesive properties of mucus is determined by both the forces applied to mucus by airflow and the mucus-airway surface properties.In NCFBE, mucus hyperviscosity contributes to impaired mucus clearance and confers to disease pathogenesis; therefore, it may be a therapeutic target. The primary objectives of physiotherapy regimens in NCFBE are mucus hydration and the establishment of an optimal expiratory airflow velocity, which exerts shearing forces on the mucus located on the airway surface. Modifying the rheological properties of mucus and enhancing its transport whenever possible (by breathing manoeuvres, ciliary activity, and cough) represent prime goals in preventing disease progression and indeed reversing bronchiectasis in the early stages of the disease, as well as preventing pulmonary exacerbations.
{"title":"Cough in Non-Cystic Fibrosis Bronchiectasis","authors":"A. Kantar, Woo-Jung Song, Andrew Bush, Grigorios Chatziparasidis","doi":"10.1183/23120541.00330-2024","DOIUrl":"https://doi.org/10.1183/23120541.00330-2024","url":null,"abstract":"Non-cystic fibrosis bronchiectasis (NCFBE) belongs to the spectrum of chronic suppurative lung diseases and is characterised by persistent wet/sputum-productive cough and airway dilatation. Morphological and structural changes in the airways lead to changes in airflow, impair breathing-induced mucus transport and sliding, and reduce the shear forces of cough. Moreover, mucus hyperviscosity contributes to compromised ciliary activity and the pathogenesis of the disease. This review highlights the role of cough in NCFBE, especially with respect to mucus clearance.Cough is the principal backup mechanism when mucus clearance is impaired due to either or both reduced function of cilia- and breathing-induced mucus transport, as well as abnormal mucus. The efficiency of cough in overcoming the cohesive and adhesive properties of mucus is determined by both the forces applied to mucus by airflow and the mucus-airway surface properties.In NCFBE, mucus hyperviscosity contributes to impaired mucus clearance and confers to disease pathogenesis; therefore, it may be a therapeutic target. The primary objectives of physiotherapy regimens in NCFBE are mucus hydration and the establishment of an optimal expiratory airflow velocity, which exerts shearing forces on the mucus located on the airway surface. Modifying the rheological properties of mucus and enhancing its transport whenever possible (by breathing manoeuvres, ciliary activity, and cough) represent prime goals in preventing disease progression and indeed reversing bronchiectasis in the early stages of the disease, as well as preventing pulmonary exacerbations.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348283","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 : 2024-06-13DOI: 10.1183/23120541.00268-2024
Else-Anna-Maria-Dorothee ter Haar, D. Slebos, K. Klooster, S. D. Pouwels, J. Hartman
Patients with chronic obstructive pulmonary disease (COPD) often present with a significant number of comorbidities, which are thought to be related to a higher mortality risk. Our aim was to investigate the prevalence and impact of comorbidities on survival and quality of life (QoL), specifically in patients with emphysema characterized by severe lung hyperinflation.Data were prospectively collected from patients, who visited our hospital for evaluating their eligibility for a bronchoscopic lung volume reduction treatment, and were included in the Groningen Severe COPD cohort (NCT04023409). Comorbidities were patient-reported by a questionnaire, and were validated with patients’ medical records. QoL was assessed with the St. Georges Respiratory Questionnaire (SGRQ).We included 830 COPD patients with GOLD stage III and IV. The total number of comorbidities was an independent predictor of survival when adjusting for other factors influencing survival (HR 1.12, 95%CI:1.05–1.20, p<0.001). Of the individual comorbidities, pulmonary arterial hypertension (HR 1.53, 95%CI:1.01–2.32, p=0.045), low body-mass index (HR 1.63, 95%CI:1.16–2.27, p=0.004), and anxiety (HR 1.46, 95%CI:1.11–1.92, p=0.007) were independently associated with worse survival. Moreover, patients having 3, 4 or >5 comorbidities had a significantly (all p<0.05) worse QoL, in comparison to patients without comorbidities.Our results show that comorbidities were associated with lower survival and poor QoL in emphysema patients characterized by severe hyperinflation. Appropriate treatment of treatable traits, including anxiety, low body-mass index, and pulmonary arterial hypertension, could lead to a survival benefit and improvement in QoL in this specific patient population.
慢性阻塞性肺病（COPD）患者通常伴有大量合并症，这被认为与较高的死亡风险有关。我们的目的是调查合并症的患病率及其对生存和生活质量（QoL）的影响，尤其是以严重肺过度充气为特征的肺气肿患者的合并症。合并症由患者通过问卷报告，并与患者的医疗记录进行验证。我们纳入了 830 名 GOLD III 期和 IV 期慢性阻塞性肺病患者。与无合并症的患者相比，合并症患者的 QoL 明显较差（均 p<0.05）。我们的研究结果表明，合并症与以严重过度充气为特征的肺气肿患者较低的生存率和较差的 QoL 相关。对焦虑、低体重指数和肺动脉高压等可治疗特征进行适当治疗，可使这一特殊患者群体的生存率提高，生活质量改善。
{"title":"Comorbidities reduce survival and quality of life in COPD with severe lung hyperinflation","authors":"Else-Anna-Maria-Dorothee ter Haar, D. Slebos, K. Klooster, S. D. Pouwels, J. Hartman","doi":"10.1183/23120541.00268-2024","DOIUrl":"https://doi.org/10.1183/23120541.00268-2024","url":null,"abstract":"Patients with chronic obstructive pulmonary disease (COPD) often present with a significant number of comorbidities, which are thought to be related to a higher mortality risk. Our aim was to investigate the prevalence and impact of comorbidities on survival and quality of life (QoL), specifically in patients with emphysema characterized by severe lung hyperinflation.Data were prospectively collected from patients, who visited our hospital for evaluating their eligibility for a bronchoscopic lung volume reduction treatment, and were included in the Groningen Severe COPD cohort (NCT04023409). Comorbidities were patient-reported by a questionnaire, and were validated with patients’ medical records. QoL was assessed with the St. Georges Respiratory Questionnaire (SGRQ).We included 830 COPD patients with GOLD stage III and IV. The total number of comorbidities was an independent predictor of survival when adjusting for other factors influencing survival (HR 1.12, 95%CI:1.05–1.20, p<0.001). Of the individual comorbidities, pulmonary arterial hypertension (HR 1.53, 95%CI:1.01–2.32, p=0.045), low body-mass index (HR 1.63, 95%CI:1.16–2.27, p=0.004), and anxiety (HR 1.46, 95%CI:1.11–1.92, p=0.007) were independently associated with worse survival. Moreover, patients having 3, 4 or >5 comorbidities had a significantly (all p<0.05) worse QoL, in comparison to patients without comorbidities.Our results show that comorbidities were associated with lower survival and poor QoL in emphysema patients characterized by severe hyperinflation. Appropriate treatment of treatable traits, including anxiety, low body-mass index, and pulmonary arterial hypertension, could lead to a survival benefit and improvement in QoL in this specific patient population.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"30 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141349975","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 : 2024-06-13DOI: 10.1183/23120541.00527-2024
Kohei Fujita, Y. Kanemitsu, H. Ohkubo, Akihito Okada, Akiko Nakano, K. Ito, Y. Mori, Kensuke Fukumitsu, S. Fukuda, T. Uemura, T. Tajiri, Y. Ito, T. Oguri, Yoshiyuki Ozawa, Takayuki Murase, Akio Niimi
{"title":"Productive cough associated with patient-reported outcomes and computed tomography analysis results in idiopathic pulmonary fibrosis: a single centre cross-sectional study","authors":"Kohei Fujita, Y. Kanemitsu, H. Ohkubo, Akihito Okada, Akiko Nakano, K. Ito, Y. Mori, Kensuke Fukumitsu, S. Fukuda, T. Uemura, T. Tajiri, Y. Ito, T. Oguri, Yoshiyuki Ozawa, Takayuki Murase, Akio Niimi","doi":"10.1183/23120541.00527-2024","DOIUrl":"https://doi.org/10.1183/23120541.00527-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"57 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347032","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 : 2024-06-13DOI: 10.1183/23120541.00199-2024
F. Mercuri, Scott White, Hayley A McQuilten, Charlotte Lemech, Stephan Mynhardt, Rana Hari, Ping Zhang, Nicole Kruger, Grant Mclachlan, Bruce.E Miller, Nicholas P. West, R. Tal-Singer, Christophe Demaison
Local priming of the innate immune system with a TLR2/6 agonist may reduce morbidity and mortality associated with viral respiratory tract infections, particularly for the elderly and those with chronic diseases.To understand the potential of prophylactic treatment with a TLR2/6 agonist as an enhancer of innate immunity pathways leading to accelerated respiratory virus clearance from the upper airways.Two randomized, double-blind, placebo-controlled clinical trials were conducted in healthy adult participants. The first dose-escalation study assessed safety, tolerability and mechanistic biomarkers following single and repeated intranasal administrations of INNA-051. The second was an Influenza A viral challenge study assessing the impact of treatment on host defence biomarkers and viral load.INNA-051 was well tolerated in both studies, with no dose-limiting toxicities identified. Mechanistic biomarkers assessed in both studies demonstrated the expected engagement of pharmacology, including innate immune pathways. There were lower than anticipated rates of infection. Post hoc analysis conducted in laboratory-confirmed infected participants with low or no antibody titre against the challenge virus showed INNA-051 treatment led to significantly shorter duration of infection and increased expression of genes and pathways associated with host defence responses against influenza.The safety and pharmacology profile of INNA-051 confirms preclinical studies. INNA-051 increased expression of genes and pathways associated with host defence responses against influenza and was associated with shorter duration of infection. These studies support further clinical assessment in the context of natural viral respiratory tract infections in individuals at increased risk of severe illness.
{"title":"Evaluation of Intranasal TLR2/6 agonist INNA-051: Safety, Tolerability and Proof of Pharmacology","authors":"F. Mercuri, Scott White, Hayley A McQuilten, Charlotte Lemech, Stephan Mynhardt, Rana Hari, Ping Zhang, Nicole Kruger, Grant Mclachlan, Bruce.E Miller, Nicholas P. West, R. Tal-Singer, Christophe Demaison","doi":"10.1183/23120541.00199-2024","DOIUrl":"https://doi.org/10.1183/23120541.00199-2024","url":null,"abstract":"Local priming of the innate immune system with a TLR2/6 agonist may reduce morbidity and mortality associated with viral respiratory tract infections, particularly for the elderly and those with chronic diseases.To understand the potential of prophylactic treatment with a TLR2/6 agonist as an enhancer of innate immunity pathways leading to accelerated respiratory virus clearance from the upper airways.Two randomized, double-blind, placebo-controlled clinical trials were conducted in healthy adult participants. The first dose-escalation study assessed safety, tolerability and mechanistic biomarkers following single and repeated intranasal administrations of INNA-051. The second was an Influenza A viral challenge study assessing the impact of treatment on host defence biomarkers and viral load.INNA-051 was well tolerated in both studies, with no dose-limiting toxicities identified. Mechanistic biomarkers assessed in both studies demonstrated the expected engagement of pharmacology, including innate immune pathways. There were lower than anticipated rates of infection. Post hoc analysis conducted in laboratory-confirmed infected participants with low or no antibody titre against the challenge virus showed INNA-051 treatment led to significantly shorter duration of infection and increased expression of genes and pathways associated with host defence responses against influenza.The safety and pharmacology profile of INNA-051 confirms preclinical studies. INNA-051 increased expression of genes and pathways associated with host defence responses against influenza and was associated with shorter duration of infection. These studies support further clinical assessment in the context of natural viral respiratory tract infections in individuals at increased risk of severe illness.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"78 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348295","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 : 2024-06-13DOI: 10.1183/23120541.00260-2024
Mi-Yeong Kim, Ha-Kyeong Won, Ji-Yoon Oh, Ji-Hyang Lee, Eun-Jung Jo, Sung-Yoon Kang, Ji-Ho Lee, Seung-Eun Lee, N. Kang, Young-Chan Kim, Hwa Young Lee, J. An, Y. Yoo, J.-S. Shim, So-Young Park, H. Park, Min-Hye Kim, Sae-Hoon Kim, Sang-Heon Kim, Yoon-Seok Chang, Sang-Hoon Kim, Byung Jae Lee, S. Birring, Woo-Jung Song
The symptoms of cough hypersensitivity do not distinguish between asthmatic cough and refractory chronic cough. Cough reflex hypersensitivity may underlie chronic cough across different phenotypes, despite having different treatable traits,Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC).Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the etiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively.The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic coughversus8.9±3.9 in RCC; p=0.215, adjusted for age, sex and and LCQ score). There were no significant between-group differences in the LCQ and cough severity VAS scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=−0.427, p<0.001; RUCC: r=−0.306, p<0.001).The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits.
{"title":"Could cough hypersensitivity symptom profile differentiate phenotypes of chronic cough?","authors":"Mi-Yeong Kim, Ha-Kyeong Won, Ji-Yoon Oh, Ji-Hyang Lee, Eun-Jung Jo, Sung-Yoon Kang, Ji-Ho Lee, Seung-Eun Lee, N. Kang, Young-Chan Kim, Hwa Young Lee, J. An, Y. Yoo, J.-S. Shim, So-Young Park, H. Park, Min-Hye Kim, Sae-Hoon Kim, Sang-Heon Kim, Yoon-Seok Chang, Sang-Hoon Kim, Byung Jae Lee, S. Birring, Woo-Jung Song","doi":"10.1183/23120541.00260-2024","DOIUrl":"https://doi.org/10.1183/23120541.00260-2024","url":null,"abstract":"The symptoms of cough hypersensitivity do not distinguish between asthmatic cough and refractory chronic cough. Cough reflex hypersensitivity may underlie chronic cough across different phenotypes, despite having different treatable traits,Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC).Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the etiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively.The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic coughversus8.9±3.9 in RCC; p=0.215, adjusted for age, sex and and LCQ score). There were no significant between-group differences in the LCQ and cough severity VAS scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=−0.427, p<0.001; RUCC: r=−0.306, p<0.001).The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"35 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141345951","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 : 2024-06-06DOI: 10.1183/23120541.00254-2024
Paweł Kukiełka, Katarzyna Moliszewska, K. Białek-Gosk, E. M. Grabczak, Marta Dąbrowska
Refractory and unexplained chronic cough (RCC; UCC) pose significant clinical challenges, impairing patients’ quality of life; however, defining RCC precisely remains elusive. Hence, this study aimed to assess RCC and UCC prevalence among patients referred to our cough centre and to analyse RCC prevalence relative to its definition.This prospective cohort study included all patients who were diagnosed at a cough clinic between 2018–2022. The response to therapy was measured based on the reduction in cough severity (viathe Visual Analogue Scale [VAS]) and improvement in cough-related quality of life (viathe Leicester cough questionnaire [LCQ]). RCC was defined as persistent cough severity, with none or minimal improvement (ΔVAS<30 mm) after ≥2 treatment attempts and cough severity ≥40/100 mm (VAS).Of 201 patients treated for chronic cough, only three (1.5%) were diagnosed with UCC. Among 166 patients monitored for therapy response, 71 (42.8%) experienced a cough severity reduction in VAS ≥30 mm, while 100 (60.2%) showed an improvement in LCQ ≥1.5 points.Based on the basic RCC definition, 51 of 166 patients (30.7%) were diagnosed. If applying stricter criteria (persistent severe cough ≥40 mm [VAS], insufficient therapy response <30 mm reduction [VAS], and <1.5 point improvement [LCQ]), RCC would be diagnosed in 45 subjects (27.1%).RCC is common in patients referred to cough clinics. The prevalence of RCC differs slightly depending on the diagnostic criteria. Therefore, it is necessary to clarify the definition of RCC used in routine practice.
{"title":"Prevalence of refractory and unexplained chronic cough in adults treated in cough centre","authors":"Paweł Kukiełka, Katarzyna Moliszewska, K. Białek-Gosk, E. M. Grabczak, Marta Dąbrowska","doi":"10.1183/23120541.00254-2024","DOIUrl":"https://doi.org/10.1183/23120541.00254-2024","url":null,"abstract":"Refractory and unexplained chronic cough (RCC; UCC) pose significant clinical challenges, impairing patients’ quality of life; however, defining RCC precisely remains elusive. Hence, this study aimed to assess RCC and UCC prevalence among patients referred to our cough centre and to analyse RCC prevalence relative to its definition.This prospective cohort study included all patients who were diagnosed at a cough clinic between 2018–2022. The response to therapy was measured based on the reduction in cough severity (viathe Visual Analogue Scale [VAS]) and improvement in cough-related quality of life (viathe Leicester cough questionnaire [LCQ]). RCC was defined as persistent cough severity, with none or minimal improvement (ΔVAS<30 mm) after ≥2 treatment attempts and cough severity ≥40/100 mm (VAS).Of 201 patients treated for chronic cough, only three (1.5%) were diagnosed with UCC. Among 166 patients monitored for therapy response, 71 (42.8%) experienced a cough severity reduction in VAS ≥30 mm, while 100 (60.2%) showed an improvement in LCQ ≥1.5 points.Based on the basic RCC definition, 51 of 166 patients (30.7%) were diagnosed. If applying stricter criteria (persistent severe cough ≥40 mm [VAS], insufficient therapy response <30 mm reduction [VAS], and <1.5 point improvement [LCQ]), RCC would be diagnosed in 45 subjects (27.1%).RCC is common in patients referred to cough clinics. The prevalence of RCC differs slightly depending on the diagnostic criteria. Therefore, it is necessary to clarify the definition of RCC used in routine practice.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"96 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141376437","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 : 2024-06-06DOI: 10.1183/23120541.00050-2024
L. Ferreiro, M. Toubes, J. Suárez-Antelo, N. Rodríguez-Núñez, Luis Valdés
In physiological conditions, the pleural space couples the lung with the chest wall and contains a small amount of fluid in continuous turnover. The volume of pleural fluid is the result from the balance between the entry of fluid through the pleural capillaries and drainage by the lymphatics in the most dependent areas of the parietal pleura. Fluid filtration is governed by Starling forces, determined by the hydrostatic and oncotic pressures of the capillaries and the pleural space. The reabsorption rate is 28 times greater than the rate of pleural fluid production. The mesothelial layer of the inner lining of the pleural space is metabolically active and also plays a role in the production and reabsorption of pleural fluid.Pleural effusion occurs when the balance between the amount of fluid that enters the pleural space and the amount that is reabsorbed is disrupted. Alterations in hydrostatic or oncotic pressure produce a transudate, but they do not cause any structural damage to the pleura. In contrast, disturbances in fluid flow (increased filtration or decreased reabsorption) produce an exudateviaseveral mechanisms that cause damage to pleural layers. Thus, cellular processes and the inflammatory and immune reactions they induce determine the composition of pleural fluid. Understanding the underlying pathophysiological processes of PE, especially cellular processes, can be useful in establishing the etiology of pleural effusion.
在生理条件下，胸膜腔将肺部与胸壁连接起来，并含有少量不断翻动的液体。胸腔积液的量是液体通过胸膜毛细血管进入胸膜与胸膜顶最依赖区域的淋巴管引流之间平衡的结果。液体过滤受斯塔林力控制，由毛细血管和胸膜腔的静水压和气压决定。重吸收率是胸腔积液产生率的 28 倍。当进入胸膜腔的液体量和被重新吸收的液体量之间的平衡被打破时，就会发生胸腔积液。静水压或气压的变化会产生渗出液，但不会对胸膜造成任何结构性损伤。相反，液体流动的紊乱（过滤增加或重吸收减少）则会产生渗出物。因此，细胞过程及其诱发的炎症和免疫反应决定了胸腔积液的成分。了解 PE 的基本病理生理过程，尤其是细胞过程，有助于确定胸腔积液的病因。
{"title":"Clinical overview of the physiology and pathophysiology of pleural fluid movement: A narrative review","authors":"L. Ferreiro, M. Toubes, J. Suárez-Antelo, N. Rodríguez-Núñez, Luis Valdés","doi":"10.1183/23120541.00050-2024","DOIUrl":"https://doi.org/10.1183/23120541.00050-2024","url":null,"abstract":"In physiological conditions, the pleural space couples the lung with the chest wall and contains a small amount of fluid in continuous turnover. The volume of pleural fluid is the result from the balance between the entry of fluid through the pleural capillaries and drainage by the lymphatics in the most dependent areas of the parietal pleura. Fluid filtration is governed by Starling forces, determined by the hydrostatic and oncotic pressures of the capillaries and the pleural space. The reabsorption rate is 28 times greater than the rate of pleural fluid production. The mesothelial layer of the inner lining of the pleural space is metabolically active and also plays a role in the production and reabsorption of pleural fluid.Pleural effusion occurs when the balance between the amount of fluid that enters the pleural space and the amount that is reabsorbed is disrupted. Alterations in hydrostatic or oncotic pressure produce a transudate, but they do not cause any structural damage to the pleura. In contrast, disturbances in fluid flow (increased filtration or decreased reabsorption) produce an exudateviaseveral mechanisms that cause damage to pleural layers. Thus, cellular processes and the inflammatory and immune reactions they induce determine the composition of pleural fluid. Understanding the underlying pathophysiological processes of PE, especially cellular processes, can be useful in establishing the etiology of pleural effusion.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":"75 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141376671","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}
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