Lisa Lancaster, Vincent Cottin, Murali Ramaswamy, Wim A Wuyts, R Gisli Jenkins, Mary Beth Scholand, Michael Kreuter, Claudia Valenzuela, Christopher J Ryerson, Jonathan Goldin, Grace Hyun J Kim, Marzena Jurek, Martin Decaris, Annie Clark, Scott M Turner, Chris N Barnes, Hardean E Achneck, Gregory P Cosgrove, Éric A Lefebvre, Kevin R Flaherty
{"title":"Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.","authors":"Lisa Lancaster, Vincent Cottin, Murali Ramaswamy, Wim A Wuyts, R Gisli Jenkins, Mary Beth Scholand, Michael Kreuter, Claudia Valenzuela, Christopher J Ryerson, Jonathan Goldin, Grace Hyun J Kim, Marzena Jurek, Martin Decaris, Annie Clark, Scott M Turner, Chris N Barnes, Hardean E Achneck, Gregory P Cosgrove, Éric A Lefebvre, Kevin R Flaherty","doi":"10.1177/17534666241287307","DOIUrl":"10.1177/17534666241287307","url":null,"abstract":"<p><p><b>What is this summary about?</b>This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the <i>American Journal of Respiratory and Critical Care Medicine</i> in 2024. This study looked at a medicine called <b>bexotegrast</b> (beck-so-teh-grast) as a possible treatment for <b>idiopathic pulmonary fibrosis</b> (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). <b>Bexotegrast</b> is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment. IPF is a chronic, progressive lung disease that makes it hard to breathe and gets worse over time. There is no cure for IPF, treatment includes symptom management and consideration for the use of <b>nintedanib</b> or <b>pirfenidone</b>, which may decrease the pace of disease progression.The study compared <b>bexotegrast</b> to a <b>placebo</b> (a treatment that looks identical to the medicine but has no medicinal effect) to look at how well it works and how safe it is in treating people with IPF. Most people in the study also took one of two medicines that are already approved by the FDA for IPF, <b>pirfenidone</b> or <b>nintedanib</b>.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241287307"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The applications of CT with artificial intelligence in the prognostic model of idiopathic pulmonary fibrosis.","authors":"Zeyu Chen, Zheng Lin, Zihan Lin, Qi Zhang, Haoyun Zhang, Haiwen Li, Qing Chang, Jianqi Sun, Feng Li","doi":"10.1177/17534666241282538","DOIUrl":"10.1177/17534666241282538","url":null,"abstract":"<p><strong>Take home message: </strong>The review summarizes the applications of CT and AI algorithms for prognostic models in IPF and procedures of model construction. It reveals the current limitations and prospects of AI-aid models, and helps clinicians to recognize the AI algorithms and apply them to more clinical work.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241282538"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrii Dudnyk, Matthias Hempel, Oksana Lytvyniuk, Halyna Liudkevych, Volodymyr Matsera, Tetiana Nikitchenko, Svitlana Blyzniuk, Barbara Molina-Moya, Rosemarie Preyer, José Domínguez
{"title":"Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.","authors":"Andrii Dudnyk, Matthias Hempel, Oksana Lytvyniuk, Halyna Liudkevych, Volodymyr Matsera, Tetiana Nikitchenko, Svitlana Blyzniuk, Barbara Molina-Moya, Rosemarie Preyer, José Domínguez","doi":"10.1177/17534666241249841","DOIUrl":"10.1177/17534666241249841","url":null,"abstract":"<p><strong>Background: </strong>Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together.</p><p><strong>Objectives: </strong>The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens.</p><p><strong>Design: </strong>A prospective observational cohort study.</p><p><strong>Methods: </strong>From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine.</p><p><strong>Results: </strong>A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (<i>p</i> < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine.</p><p><strong>Conclusion: </strong>Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241249841"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alberto Papi, Rod Hughes, Ricardo Del Olmo, Alvar Agusti, Bradley E Chipps, Barry Make, Erin Tomaszewski, Keith Peres Da Costa, Divyansh Srivastava, Jørgen Vestbo, Christer Janson, Pierre-Régis Burgel, David Price
{"title":"Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a real-life setting: the NOVEL observational longiTudinal studY.","authors":"Alberto Papi, Rod Hughes, Ricardo Del Olmo, Alvar Agusti, Bradley E Chipps, Barry Make, Erin Tomaszewski, Keith Peres Da Costa, Divyansh Srivastava, Jørgen Vestbo, Christer Janson, Pierre-Régis Burgel, David Price","doi":"10.1177/17534666241254212","DOIUrl":"10.1177/17534666241254212","url":null,"abstract":"<p><strong>Background: </strong>The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain.</p><p><strong>Objectives: </strong>To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD.</p><p><strong>Design: </strong>The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study.</p><p><strong>Methods: </strong>Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1.</p><p><strong>Results: </strong>A total of 11,181 patients in NOVELTY had spirometry data (asthma, <i>n</i> = 5903; COPD, <i>n</i> = 3881; asthma + COPD, <i>n</i> = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV<sub>1</sub>) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV<sub>1</sub> and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma.</p><p><strong>Conclusion: </strong>In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma.</p><p><strong>Trail registration: </strong>clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241254212"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amin Hosseini Nami, Mahboubeh Kabiri, Fatemeh Zafarghandi Motlagh, Tina Shirzadeh, Hamideh Bagherian, Razie Zeinali, Ali Karimi, Sirous Zeinali
{"title":"Identification and <i>in silico</i> structural analysis for the first <i>de novo</i> mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers.","authors":"Amin Hosseini Nami, Mahboubeh Kabiri, Fatemeh Zafarghandi Motlagh, Tina Shirzadeh, Hamideh Bagherian, Razie Zeinali, Ali Karimi, Sirous Zeinali","doi":"10.1177/17534666241253990","DOIUrl":"10.1177/17534666241253990","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and <i>in silico</i> studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the <i>de novo</i> nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The <i>de novo</i> mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to <i>in silico</i> structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of <i>de novo</i> mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241253990"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis.","authors":"Isabel Mira-Avendano, Mitchell Kaye","doi":"10.1177/17534666241266343","DOIUrl":"10.1177/17534666241266343","url":null,"abstract":"<p><p>In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241266343"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Aljama, Teresa Martin, Galo Granados, Marc Miravitlles, Miriam Barrecheguren
{"title":"Personalised indication of augmentation therapy for emphysema associated with severe alpha-1 antitrypsin deficiency: a case series.","authors":"Cristina Aljama, Teresa Martin, Galo Granados, Marc Miravitlles, Miriam Barrecheguren","doi":"10.1177/17534666241271917","DOIUrl":"10.1177/17534666241271917","url":null,"abstract":"<p><p>Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241271917"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Amati, Gloria Leonardi, Martina Contarini, Letizia Corinna Morlacchi, Anna Stainer, Giovanna Pizzamiglio, Stefano Aliberti, Francesco Blasi, Andrea Gramegna
{"title":"Immunodeficiencies and CFTR dysfunction: results from a systematic screening in a cohort of adults with cystic fibrosis and CFTR-related disorders.","authors":"Francesco Amati, Gloria Leonardi, Martina Contarini, Letizia Corinna Morlacchi, Anna Stainer, Giovanna Pizzamiglio, Stefano Aliberti, Francesco Blasi, Andrea Gramegna","doi":"10.1177/17534666241253945","DOIUrl":"10.1177/17534666241253945","url":null,"abstract":"<p><strong>Background: </strong>Immunodeficiencies (IDs) are conditions caused by immune system dysfunctions which predispose to chronic infections. Cystic fibrosis (CF) patients are characterized by the presence of bronchiectasis filled with hyper-viscous secretions that constitute the ideal environment for infections. Although CF and IDs might share similarities in the pathophysiological mechanism of bronchiectasis development, they each offer different treatment options. We hypothesize that the introduction of a bundle of tests would increase the number of ID diagnoses among adults with Cystic Fibrosis Transmembrane conductance Regulator (CFTR) dysfunction.</p><p><strong>Objectives: </strong>The primary objectives of this study were (1) assessing the prevalence of IDs in CF and (2) defining clinical characteristics of adults with both CF and IDs. The secondary objectives were: (1) assessing the prevalence of IDs in CFTR-Related Disorder (CFTR-RD) patients; (2) comparing the prevalence of IDs in CF and CFTR-RD; (3) comparing the prevalence of treatable IDs in CF and CFTR-RD.</p><p><strong>Design: </strong>We conducted an observational, prospective, consecutive study on a cohort of 190 adult patients affected by CF or CFTR-RD.</p><p><strong>Methods: </strong>Blood samples underwent a standardized immunological screening, including complete white blood count, IgG, IgA, IgM, IgG subclasses, total IgE, lymphocyte subsets, and HIV test. Comprehensive clinical history was assessed to identify risk factors for secondary IDs.</p><p><strong>Results: </strong>We identify a high prevalence of immunodeficiencies among the entire cohort: 34 (20.1%) CF patients and 10 (47.6%) CFTR-RD patients are diagnosed with IDs <i>via</i> a blood screening. No statistically significant difference in terms of clinical characteristics was found between immunocompromised and immunocompetent CF patients.</p><p><strong>Conclusion: </strong>We identify a high prevalence of immunodeficiencies in both CF and CFTR-RD.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241253945"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Zhang, Mengru Zhang, Alimire Aierken, Ran Dong, Qiang Chen, Zhongmin Qiu
{"title":"Role of alveolar nitric oxide in gastroesophageal reflux-associated cough: prospective observational study.","authors":"Li Zhang, Mengru Zhang, Alimire Aierken, Ran Dong, Qiang Chen, Zhongmin Qiu","doi":"10.1177/17534666241231117","DOIUrl":"10.1177/17534666241231117","url":null,"abstract":"<p><strong>Background: </strong>Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC).</p><p><strong>Objectives: </strong>We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC.</p><p><strong>Design: </strong>This is a single-center prospective observational study.</p><p><strong>Methods: </strong>FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO.</p><p><strong>Results: </strong>CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb <i>versus</i> 2.8 ± 2.3 ppb, <i>p</i> < 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15 <i>versus</i> 9 ± 9 episodes, <i>p</i> = 0.001) and a higher level of pepsin (984.8 ± 492.5 <i>versus</i> 634.5 ± 626.4 pg/ml, <i>p</i> = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ<sup>2</sup> = 3.963, <i>p</i> = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 <i>versus</i> 4.8 ± 2.6 ppb, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241231117"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Hou, Yu Nie, Yiqiong Wen, Shu Hua, Yunjiao Hou, Huilin He, Shibo Sun
{"title":"The role and mechanism of AMPK in pulmonary hypertension.","authors":"Jing Hou, Yu Nie, Yiqiong Wen, Shu Hua, Yunjiao Hou, Huilin He, Shibo Sun","doi":"10.1177/17534666241271990","DOIUrl":"10.1177/17534666241271990","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, β, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"18 ","pages":"17534666241271990"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}