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}
Pub Date : 2023-03-01DOI: 10.1007/s41030-022-00213-9
Haley Lynn, Melisa Wilson
Pulmonary arterial hypertension (PAH) is a rare disease caused by high pressure in the blood vessels leading from the heart to the lung. PAH affects many parts of a patient's life, which means that patients should be managed by a clinical team of different specialists, including doctors, advance practice providers, nurses, social workers, and therapists. This article is co-authored by a patient living with PAH and an acute care nurse practitioner specializing in the management of patients with pulmonary hypertension. In the first section of this commentary, the patient describes her experience of living with PAH. The specialist nurse practitioner then discusses the management of PAH, to provide a clinician perspective in the context of the patient's experiences.
{"title":"Why Living with Pulmonary Arterial Hypertension Requires a Holistic Approach: A Patient and Clinician Perspective.","authors":"Haley Lynn, Melisa Wilson","doi":"10.1007/s41030-022-00213-9","DOIUrl":"https://doi.org/10.1007/s41030-022-00213-9","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare disease caused by high pressure in the blood vessels leading from the heart to the lung. PAH affects many parts of a patient's life, which means that patients should be managed by a clinical team of different specialists, including doctors, advance practice providers, nurses, social workers, and therapists. This article is co-authored by a patient living with PAH and an acute care nurse practitioner specializing in the management of patients with pulmonary hypertension. In the first section of this commentary, the patient describes her experience of living with PAH. The specialist nurse practitioner then discusses the management of PAH, to provide a clinician perspective in the context of the patient's experiences.</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/d5/54/41030_2022_Article_213.PMC9931975.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10740986","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/s41030-023-00214-2
Patrick M Wieruszewski, Jamel P Ortoleva, Daniel S Cormican, Troy G Seelhammer
Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation.
{"title":"Extracorporeal Membrane Oxygenation in Acute Respiratory Failure.","authors":"Patrick M Wieruszewski, Jamel P Ortoleva, Daniel S Cormican, Troy G Seelhammer","doi":"10.1007/s41030-023-00214-2","DOIUrl":"https://doi.org/10.1007/s41030-023-00214-2","url":null,"abstract":"<p><p>Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation.</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/9a/e7/41030_2023_Article_214.PMC9859746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296723","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 : 2023-03-01Epub Date: 2022-12-02DOI: 10.1007/s41030-022-00204-w
Priscilla Ng, Herng Lee Tan, Yi-Jyun Ma, Rehena Sultana, Victoria Long, Judith J-M Wong, Jan Hau Lee
Introduction: There is lack of consensus on what constitutes best practice when assessing extubation readiness in children. This systematic review aims to synthesize data from existing literature on pre-extubation assessments and evaluate their diagnostic accuracies in predicting extubation failure (EF) in children.
Methods: A systematic search in PubMed, EMBASE, Web of Science, CINAHL, and Cochrane was performed from inception of each database to 15 July 2021. Randomized controlled trials or observational studies that studied the association between pre-extubation assessments and extubation outcome in the pediatric intensive care unit population were included. Meta-analysis was performed for studies that report diagnostic tests results of a combination of parameters.
Results: In total, 41 of 11,663 publications screened were included (total patients, n = 8111). Definition of EF across studies was heterogeneous. Fifty-five unique pre-extubation assessments were identified. Parameters most studied were: respiratory rate (RR) (13/41, n = 1945), partial pressure of arterial carbon dioxide (10/41, n = 1379), tidal volume (13/41, n = 1945), rapid shallow breathing index (RBSI) (9/41, n = 1400), and spontaneous breathing trials (SBT) (13/41, n = 5652). Meta-analysis shows that RSBI, compliance rate oxygenation pressure (CROP) index, and SBT had sensitivities ranging from 0.14 to 0.57. CROP index had the highest sensitivity [0.57, 95% confidence interval (CI) 0.4-0.73] and area under curve (AUC, 0.98). SBT had the highest specificity (0.93, 95% CI 0.92-0.94).
Conclusions: Pre-extubation assessments studied thus far remain poor predictors of EF. CROP index, having the highest AUC, should be further explored as a predictor of EF. Standardizing the EF definition will allow better comparison of pre-extubation assessments.
导言:在评估儿童拔管准备情况时,对于什么是最佳做法缺乏共识。本系统性综述旨在综合现有文献中有关拔管前评估的数据,并评估其在预测儿童拔管失败(EF)方面的诊断准确性:方法:在 PubMed、EMBASE、Web of Science、CINAHL 和 Cochrane 中进行了系统性检索,检索时间从各数据库建立之初至 2021 年 7 月 15 日。纳入了研究儿科重症监护室人群拔管前评估与拔管结果之间关系的随机对照试验或观察性研究。对报告诊断测试结果的综合参数的研究进行了 Meta 分析:在筛选出的 11,663 篇文献中,共有 41 篇被纳入研究(患者总数为 8111 人)。各研究对 EF 的定义不尽相同。确定了 55 项独特的拔管前评估。研究最多的参数是:呼吸频率 (RR) (13/41, n = 1945)、动脉二氧化碳分压 (10/41, n = 1379)、潮气量 (13/41, n = 1945)、快速浅呼吸指数 (RBSI) (9/41, n = 1400) 和自主呼吸试验 (SBT) (13/41, n = 5652)。元分析表明,RSBI、顺应率氧合压力(CROP)指数和 SBT 的灵敏度从 0.14 到 0.57 不等。CROP 指数的灵敏度最高[0.57,95% 置信区间(CI)0.4-0.73],曲线下面积(AUC,0.98)也最高。SBT的特异性最高(0.93,95% CI 0.92-0.94):结论:迄今为止研究的拔管前评估仍不能很好地预测 EF。CROP指数的AUC最高,应进一步将其作为预测EF的指标。EF 定义的标准化将有助于更好地比较拔管前评估。
{"title":"Tests and Indices Predicting Extubation Failure in Children: A Systematic Review and Meta-analysis.","authors":"Priscilla Ng, Herng Lee Tan, Yi-Jyun Ma, Rehena Sultana, Victoria Long, Judith J-M Wong, Jan Hau Lee","doi":"10.1007/s41030-022-00204-w","DOIUrl":"10.1007/s41030-022-00204-w","url":null,"abstract":"<p><strong>Introduction: </strong>There is lack of consensus on what constitutes best practice when assessing extubation readiness in children. This systematic review aims to synthesize data from existing literature on pre-extubation assessments and evaluate their diagnostic accuracies in predicting extubation failure (EF) in children.</p><p><strong>Methods: </strong>A systematic search in PubMed, EMBASE, Web of Science, CINAHL, and Cochrane was performed from inception of each database to 15 July 2021. Randomized controlled trials or observational studies that studied the association between pre-extubation assessments and extubation outcome in the pediatric intensive care unit population were included. Meta-analysis was performed for studies that report diagnostic tests results of a combination of parameters.</p><p><strong>Results: </strong>In total, 41 of 11,663 publications screened were included (total patients, n = 8111). Definition of EF across studies was heterogeneous. Fifty-five unique pre-extubation assessments were identified. Parameters most studied were: respiratory rate (RR) (13/41, n = 1945), partial pressure of arterial carbon dioxide (10/41, n = 1379), tidal volume (13/41, n = 1945), rapid shallow breathing index (RBSI) (9/41, n = 1400), and spontaneous breathing trials (SBT) (13/41, n = 5652). Meta-analysis shows that RSBI, compliance rate oxygenation pressure (CROP) index, and SBT had sensitivities ranging from 0.14 to 0.57. CROP index had the highest sensitivity [0.57, 95% confidence interval (CI) 0.4-0.73] and area under curve (AUC, 0.98). SBT had the highest specificity (0.93, 95% CI 0.92-0.94).</p><p><strong>Conclusions: </strong>Pre-extubation assessments studied thus far remain poor predictors of EF. CROP index, having the highest AUC, should be further explored as a predictor of EF. Standardizing the EF definition will allow better comparison of pre-extubation assessments.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/e3/41030_2022_Article_204.PMC9931987.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534070","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}