Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not established. Opposing acute respiratory distress syndrome (ARDS) can be proposed as a probable mechanism for the action of famotidine, due to its inhibitory effect on histamine release, inhibition of transmembrane protease serine S (TMPRSS) and stabilizing glycocalyx. These hypotheses should be under investigation in the future.
{"title":"Effect of Famotidine on COVID-19: Killing Virus or Opposing ARDS?","authors":"Mahnaz Sadat Hosseini, Effat Davoudi-Monfared, Farhad Najmeddin, Mojtaba Mojtahedzadeh","doi":"10.1007/s41030-023-00220-4","DOIUrl":"https://doi.org/10.1007/s41030-023-00220-4","url":null,"abstract":"<p><p>Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not established. Opposing acute respiratory distress syndrome (ARDS) can be proposed as a probable mechanism for the action of famotidine, due to its inhibitory effect on histamine release, inhibition of transmembrane protease serine S (TMPRSS) and stabilizing glycocalyx. These hypotheses should be under investigation in the future.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/a5/41030_2023_Article_220.PMC10066957.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9770352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1007/s41030-023-00215-1
Debora Valecchi, Elena Bargagli, Maria Grazia Pieroni, Metella Rosa Refini, Piersante Sestini, Paola Rottoli, Andrea S Melani
Introduction: Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear.
Methods: After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course.
Results: Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course.
Conclusion: We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.
{"title":"Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases.","authors":"Debora Valecchi, Elena Bargagli, Maria Grazia Pieroni, Metella Rosa Refini, Piersante Sestini, Paola Rottoli, Andrea S Melani","doi":"10.1007/s41030-023-00215-1","DOIUrl":"https://doi.org/10.1007/s41030-023-00215-1","url":null,"abstract":"<p><strong>Introduction: </strong>Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear.</p><p><strong>Methods: </strong>After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course.</p><p><strong>Results: </strong>Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course.</p><p><strong>Conclusion: </strong>We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/87/41030_2023_Article_215.PMC10203065.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1007/s41030-023-00224-0
Bao Le-Khac, Quoc-Khanh Tran-Le, Lam Nguyen-Ho, Sy Duong-Quy
Pulmonary alveolar proteinosis (PAP) is an uncommon disease and its diagnosis remains challenging. During the COVID-19 pandemic, it has been difficult to distinguish between PAP and post-COVID-19 pulmonary sequelae. Here we present a case of a 44-year-old male patient who experienced exertional dyspnea after recovering from COVID-19. He was initially diagnosed with post-COVID-19 syndrome and treated with systemic corticosteroid without improvement. Chest computed tomography (CT) showed crazy-paving pattern with ground-glass opacities. Fibreoptic bronchoscopy with bronchial lavage fluid (BLF) analysis confirmed the final diagnosis of PAP. The patient underwent left lung lavage in combination with conventional therapy and experienced significant improvement in his respiratory condition and overall health during follow-up. Hence, PAP could occur after a COVID-19 infection. This case highlights the importance of considering PAP as a potential diagnosis in patients with persistent respiratory symptoms after COVID-19. The high suspicion indicators of PAP revealed by chest-CT and BLF may be a key to differentiating PAP from post-COVID-19 pulmonary sequelae. Moreover, it is plausible that SARS-CoV-2 plays a role in the development of proteinosis, either by inducing a flare-up or by directly causing the condition.
{"title":"Post-COVID-19 Pulmonary Alveolar Proteinosis Treated Successfully with Whole Lung Lavage: A Rare Case Report.","authors":"Bao Le-Khac, Quoc-Khanh Tran-Le, Lam Nguyen-Ho, Sy Duong-Quy","doi":"10.1007/s41030-023-00224-0","DOIUrl":"https://doi.org/10.1007/s41030-023-00224-0","url":null,"abstract":"<p><p>Pulmonary alveolar proteinosis (PAP) is an uncommon disease and its diagnosis remains challenging. During the COVID-19 pandemic, it has been difficult to distinguish between PAP and post-COVID-19 pulmonary sequelae. Here we present a case of a 44-year-old male patient who experienced exertional dyspnea after recovering from COVID-19. He was initially diagnosed with post-COVID-19 syndrome and treated with systemic corticosteroid without improvement. Chest computed tomography (CT) showed crazy-paving pattern with ground-glass opacities. Fibreoptic bronchoscopy with bronchial lavage fluid (BLF) analysis confirmed the final diagnosis of PAP. The patient underwent left lung lavage in combination with conventional therapy and experienced significant improvement in his respiratory condition and overall health during follow-up. Hence, PAP could occur after a COVID-19 infection. This case highlights the importance of considering PAP as a potential diagnosis in patients with persistent respiratory symptoms after COVID-19. The high suspicion indicators of PAP revealed by chest-CT and BLF may be a key to differentiating PAP from post-COVID-19 pulmonary sequelae. Moreover, it is plausible that SARS-CoV-2 plays a role in the development of proteinosis, either by inducing a flare-up or by directly causing the condition.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/3e/41030_2023_Article_224.PMC10173208.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9770373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1007/s41030-023-00219-x
Sy Duong-Quy, Duc Huynh-Truong-Anh, Tien Nguyen-Quang, Thanh Nguyen-Thi-Kim, Thuy Tran-Ngoc-Anh, Nam Nguyen-Van-Hoai, Mai Do-Thi-Thu, Tinh Nguyen-Van, Tram Tang-Thi-Thao, Anh Nguyen-Tuan, Toi Nguyen-Van, Quynh Tran-Xuan, Quan Vu-Tran-Thien, The Trinh-Du, Tuan Tran-Thai, Thai Nguyen-Duy, Huong Tran-Van, Anh Vo-Thi-Kim
Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain-Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO2 decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination.
{"title":"Guillain-Barré Syndrome due to COVID-19 Vero Cell Vaccination Associated with Concomitant COVID-19 Infection-induced ARDS and Treated Successfully by Therapeutic Plasma Exchange: A First Case Report from Vietnam.","authors":"Sy Duong-Quy, Duc Huynh-Truong-Anh, Tien Nguyen-Quang, Thanh Nguyen-Thi-Kim, Thuy Tran-Ngoc-Anh, Nam Nguyen-Van-Hoai, Mai Do-Thi-Thu, Tinh Nguyen-Van, Tram Tang-Thi-Thao, Anh Nguyen-Tuan, Toi Nguyen-Van, Quynh Tran-Xuan, Quan Vu-Tran-Thien, The Trinh-Du, Tuan Tran-Thai, Thai Nguyen-Duy, Huong Tran-Van, Anh Vo-Thi-Kim","doi":"10.1007/s41030-023-00219-x","DOIUrl":"https://doi.org/10.1007/s41030-023-00219-x","url":null,"abstract":"<p><p>Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain-Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO<sub>2</sub> decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/95/41030_2023_Article_219.PMC10057680.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic thromboembolic pulmonary disease (CTEPD) is characterized by unresolved clot burden in large pulmonary arteries, obstructive disease in smaller arteries, and increased downstream clot burden. This occurs in the setting of abnormal fibrinolysis or hematological disorders. Up to 50% of patients in some studies are unaware of a self-history of a deep venous thrombosis or pulmonary embolism. Ultimately, they present with symptoms of pulmonary hypertension (PH), which can result in right heart failure (RHF). Pulmonary endarterectomy (PEA) is curative, though many patients have prohibitive surgical risk or surgically inaccessible disease, warranting other interventions such as balloon pulmonary angioplasty (BPA) and medical therapy. Rarely, other treatment options may be implemented. We focus this review on PEA and BPA, with an overview of the history of CTEPD and the evolution of these procedures. We will briefly discuss other treatment modalities.
{"title":"Surgical and Device Interventions in the Treatment of Chronic Thromboembolic Disease.","authors":"Hayah Kassis-George, Candice Lee, Mithun Chakravarthy, Manreet Kanwar","doi":"10.1007/s41030-023-00217-z","DOIUrl":"https://doi.org/10.1007/s41030-023-00217-z","url":null,"abstract":"<p><p>Chronic thromboembolic pulmonary disease (CTEPD) is characterized by unresolved clot burden in large pulmonary arteries, obstructive disease in smaller arteries, and increased downstream clot burden. This occurs in the setting of abnormal fibrinolysis or hematological disorders. Up to 50% of patients in some studies are unaware of a self-history of a deep venous thrombosis or pulmonary embolism. Ultimately, they present with symptoms of pulmonary hypertension (PH), which can result in right heart failure (RHF). Pulmonary endarterectomy (PEA) is curative, though many patients have prohibitive surgical risk or surgically inaccessible disease, warranting other interventions such as balloon pulmonary angioplasty (BPA) and medical therapy. Rarely, other treatment options may be implemented. We focus this review on PEA and BPA, with an overview of the history of CTEPD and the evolution of these procedures. We will briefly discuss other treatment modalities.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/b0/41030_2023_Article_217.PMC10203076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00209-5
Matthew G Hartwig, Jacob A Klapper, Nagaraju Poola, Amit Banga, Pablo G Sanchez, John S Murala, Jim L Potenziano
Introduction: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health.
Methods: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2).
Results: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group.
Conclusions: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.
{"title":"A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs.","authors":"Matthew G Hartwig, Jacob A Klapper, Nagaraju Poola, Amit Banga, Pablo G Sanchez, John S Murala, Jim L Potenziano","doi":"10.1007/s41030-022-00209-5","DOIUrl":"https://doi.org/10.1007/s41030-022-00209-5","url":null,"abstract":"<p><strong>Introduction: </strong>Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health.</p><p><strong>Methods: </strong>A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO<sub>2</sub>).</p><p><strong>Results: </strong>Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO<sub>2</sub> compared to the P group.</p><p><strong>Conclusions: </strong>The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/64/41030_2022_Article_209.PMC9744669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10726097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00205-9
Hanh Nguyen-Thi-Bich, Thuy Nguyen-Thi-Dieu, Le Nguyen-Ngoc-Quynh, Huong Le-Thi-Minh, Sy Duong-Quy
Introduction: Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness.
Methods: This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV1) after treatment versus at inclusion.
Results: In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters.
Conclusion: TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV1.
{"title":"Responsiveness of Inhaled Corticosteroid Treatment in Children with Asthma: The Role of rs242941 Polymorphism of CRHR1 Gene.","authors":"Hanh Nguyen-Thi-Bich, Thuy Nguyen-Thi-Dieu, Le Nguyen-Ngoc-Quynh, Huong Le-Thi-Minh, Sy Duong-Quy","doi":"10.1007/s41030-022-00205-9","DOIUrl":"https://doi.org/10.1007/s41030-022-00205-9","url":null,"abstract":"<p><strong>Introduction: </strong>Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness.</p><p><strong>Methods: </strong>This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV<sub>1</sub>) after treatment versus at inclusion.</p><p><strong>Results: </strong>In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters.</p><p><strong>Conclusion: </strong>TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV<sub>1</sub>.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/28/41030_2022_Article_205.PMC9931962.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10730107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00212-w
Sufyan Shakir, Brian Choo-Kang, Clare Ross, Kevin Conroy, Richard Thorley, Steven Walker, Rahul Bhatnagar, Avinash Aujayeb
Introduction: Treatment of prolonged air leak due to secondary spontaneous pneumothorax is challenging. Autologous blood patch pleurodesis (ABPP) is a treatment option. Previous evidence is reliant on single-centre series and underpowered trials and is mostly described in air leaks post cardiothoracic intervention. There are no United Kingdom (UK) wide data.
Methods: Members of the UK Pleural Society were surveyed for their practice and for patients who underwent blood patch. There were 16 respondents from 333 members. Twelve had performed the procedure, and six had kept records and could submit data. Basic demographics, intervention and clinical details of patients were then collected. The study was sponsored by the Audit Department of Northumbria Healthcare NHS Foundation Trust (reference 8124), and Caldicott Clearance for data sharing was provided by the Trust's Information Goverance Board (reference C4221). There was no requirement for informed consent.
Results: Data for 12 patients that received ABPP between 2014 and 2022 in six respiratory centres were assessed. The aetiology of the secondary pneumothoraces was mostly due to chronic obstructive pulmonary disease and end-stage interstitial lung disease. The patients had a median age of 75 years. The median air leak time before ABPP was 17 days. A total of 50-100 ml of blood was used for ABPP. Five patients had two attempts at ABPP. Air leak resolved in six patients (50%). Four patients had pleural apposition prior to ABPP. Four patients were diagnosed with hospital-acquired pneumonia following ABPP.
Conclusion: This is the only UK-wide retrospective case series of ABPP of 'medical' patients with secondary pneumothorax. There is widespread variation in care. No formal conclusions can be drawn, and much larger robust datasets are required. An application has been made to the European Respiratory Society to incorporate ABPP within the International Collaborative Effusion database.
{"title":"Autologous Blood Patch Pleurodesis for Secondary Spontaneous Pneumothorax: A Narrative Review, a Retrospective Case Series and State of Play in the UK.","authors":"Sufyan Shakir, Brian Choo-Kang, Clare Ross, Kevin Conroy, Richard Thorley, Steven Walker, Rahul Bhatnagar, Avinash Aujayeb","doi":"10.1007/s41030-022-00212-w","DOIUrl":"https://doi.org/10.1007/s41030-022-00212-w","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment of prolonged air leak due to secondary spontaneous pneumothorax is challenging. Autologous blood patch pleurodesis (ABPP) is a treatment option. Previous evidence is reliant on single-centre series and underpowered trials and is mostly described in air leaks post cardiothoracic intervention. There are no United Kingdom (UK) wide data.</p><p><strong>Methods: </strong>Members of the UK Pleural Society were surveyed for their practice and for patients who underwent blood patch. There were 16 respondents from 333 members. Twelve had performed the procedure, and six had kept records and could submit data. Basic demographics, intervention and clinical details of patients were then collected. The study was sponsored by the Audit Department of Northumbria Healthcare NHS Foundation Trust (reference 8124), and Caldicott Clearance for data sharing was provided by the Trust's Information Goverance Board (reference C4221). There was no requirement for informed consent.</p><p><strong>Results: </strong>Data for 12 patients that received ABPP between 2014 and 2022 in six respiratory centres were assessed. The aetiology of the secondary pneumothoraces was mostly due to chronic obstructive pulmonary disease and end-stage interstitial lung disease. The patients had a median age of 75 years. The median air leak time before ABPP was 17 days. A total of 50-100 ml of blood was used for ABPP. Five patients had two attempts at ABPP. Air leak resolved in six patients (50%). Four patients had pleural apposition prior to ABPP. Four patients were diagnosed with hospital-acquired pneumonia following ABPP.</p><p><strong>Conclusion: </strong>This is the only UK-wide retrospective case series of ABPP of 'medical' patients with secondary pneumothorax. There is widespread variation in care. No formal conclusions can be drawn, and much larger robust datasets are required. An application has been made to the European Respiratory Society to incorporate ABPP within the International Collaborative Effusion database.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/74/41030_2022_Article_212.PMC9931973.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10747424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00206-8
Cathy K Gelotte, Dolly A Parasrampuria, Brenda A Zimmerman
Introduction: Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2-17 years.
Methods: Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight-age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods.
Results: Mean phenylephrine total exposure (AUC∞) for children aged 2-5, 6-11, and 12-17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (Cmax) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (Tmax) ranged from 0.17 to 1.5 h, and elimination half-life (t½,β) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,scaled) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed.
Conclusion: A dosing schedule with additional weight-age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and Cmax for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. TRIAL REGISTRATION: Clintrials.gov NCT00762567, registered 30 September 2008.
{"title":"Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents.","authors":"Cathy K Gelotte, Dolly A Parasrampuria, Brenda A Zimmerman","doi":"10.1007/s41030-022-00206-8","DOIUrl":"https://doi.org/10.1007/s41030-022-00206-8","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2-17 years.</p><p><strong>Methods: </strong>Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight-age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods.</p><p><strong>Results: </strong>Mean phenylephrine total exposure (AUC<sub>∞</sub>) for children aged 2-5, 6-11, and 12-17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (C<sub>max</sub>) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (T<sub>max</sub>) ranged from 0.17 to 1.5 h, and elimination half-life (t<sub>½,β</sub>) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,<sub>scaled</sub>) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed.</p><p><strong>Conclusion: </strong>A dosing schedule with additional weight-age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and C<sub>max</sub> for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. TRIAL REGISTRATION: Clintrials.gov NCT00762567, registered 30 September 2008.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/1d/41030_2022_Article_206.PMC9931972.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9290393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00211-x
Derek Ge, Dinah Foer, Katherine N Cahill
Adults with obesity may develop asthma that is ineffectively controlled by inhaled corticosteroids and long-acting beta-adrenoceptor agonists. Mechanistic and translational studies suggest that metabolic dysregulation that occurs with obesity, particularly hyperglycemia and insulin resistance, contributes to altered immune cell function and low-grade systemic inflammation. Importantly, in these cases, the same proinflammatory cytokines believed to contribute to insulin resistance may also be responsible for airway remodeling and hyperresponsiveness. In the past decade, new research has emerged assessing whether hypoglycemic therapies impact comorbid asthma as reflected by the incidence of asthma, asthma-related emergency department visits, asthma-related hospitalizations, and asthma-related exacerbations. The purpose of this review article is to discuss the mechanism of action, preclinical data, and existing clinical studies regarding the efficacy and safety of hypoglycemic therapies for adults with obesity and comorbid asthma.
{"title":"Utility of Hypoglycemic Agents to Treat Asthma with Comorbid Obesity.","authors":"Derek Ge, Dinah Foer, Katherine N Cahill","doi":"10.1007/s41030-022-00211-x","DOIUrl":"https://doi.org/10.1007/s41030-022-00211-x","url":null,"abstract":"<p><p>Adults with obesity may develop asthma that is ineffectively controlled by inhaled corticosteroids and long-acting beta-adrenoceptor agonists. Mechanistic and translational studies suggest that metabolic dysregulation that occurs with obesity, particularly hyperglycemia and insulin resistance, contributes to altered immune cell function and low-grade systemic inflammation. Importantly, in these cases, the same proinflammatory cytokines believed to contribute to insulin resistance may also be responsible for airway remodeling and hyperresponsiveness. In the past decade, new research has emerged assessing whether hypoglycemic therapies impact comorbid asthma as reflected by the incidence of asthma, asthma-related emergency department visits, asthma-related hospitalizations, and asthma-related exacerbations. The purpose of this review article is to discuss the mechanism of action, preclinical data, and existing clinical studies regarding the efficacy and safety of hypoglycemic therapies for adults with obesity and comorbid asthma.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/f0/41030_2022_Article_211.PMC9931991.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}