-
Chest Nov 2022In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have... (Review)
Review
In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance. Although much attention has been paid to pharmacologic treatment of mechanical abnormalities in COPD (eg, bronchodilators to deflate the lungs), increasing neurochemical afferent activity, secondary to gas-exchange inefficiency, has remained elusive as a therapeutic target. Hence, in this invited review, we first summarize how dyspnea, leading to poor exercise tolerance in COPD, may be explained by an increased venous admixture resulting from low V˙A/Q˙c, or wasted ventilation related to high V˙A/Q˙c, or both. We review the conflicting evidence supporting current treatments for gas-exchange inefficiency and exercise tolerance that act primarily on V˙A (bronchodilators, antiinflammatory medications) or Q˙c (oral and inhaled vasodilators, almitrine, and supplemental oxygen). Finally, to address the current knowledge and health care gaps, we propose two independent clinical research foci that may lead to a better understanding of the role of pulmonary gas-exchange inefficiency and activity-related dyspnea in COPD: (1) enhanced and deeper phenotyping of patients with COPD with V˙A/Q˙c abnormalities and (2) evaluation of existing and novel pharmacologic treatments to improve gas-exchange inefficiency, exertional dyspnea, and exercise tolerance across the spectrum of COPD severity.
Topics: Humans; Bronchodilator Agents; Pulmonary Disease, Chronic Obstructive; Exercise Test; Exercise; Pulmonary Gas Exchange; Exercise Tolerance; Dyspnea
PubMed: 35390329
DOI: 10.1016/j.chest.2022.03.033 -
Journal of Infection and Public Health Feb 2022To clarify the work done by using AI for identifying the genomic sequences, development of drugs and vaccines for COVID-19 and to recognize the advantages and challenges... (Review)
Review
OBJECTIVES
To clarify the work done by using AI for identifying the genomic sequences, development of drugs and vaccines for COVID-19 and to recognize the advantages and challenges of using such technology.
METHODS
A non-systematic review was done. All articles published on Pub-Med, Medline, Google, and Google Scholar on AI or digital health regarding genomic sequencing, drug development, and vaccines of COVID-19 were scrutinized and summarized.
RESULTS
The sequence of SARS- CoV-2 was identified with the help of AI. It can help also in the prompt identification of variants of concern (VOC) as delta strains and Omicron. Furthermore, there are many drugs applied with the help of AI. These drugs included Atazanavir, Remdesivir, Efavirenz, Ritonavir, and Dolutegravir, PARP1 inhibitors (Olaparib and CVL218 which is Mefuparib hydrochloride), Abacavir, Roflumilast, Almitrine, and Mesylate. Many vaccines were developed utilizing the new technology of bioinformatics, databases, immune-informatics, machine learning, and reverse vaccinology to the whole SARS-CoV-2 proteomes or the structural proteins. Examples of these vaccines are the messenger RNA and viral vector vaccines. AI provides cost-saving and agility. However, the challenges of its usage are the difficulty of collecting data, the internal and external validation, ethical consideration, therapeutic effect, and the time needed for clinical trials after drug approval. Moreover, there is a common problem in the deep learning (DL) model which is the shortage of interpretability.
CONCLUSION
The growth of AI techniques in health care opened a broad gate for discovering the genomic sequences of the COVID-19 virus and the VOC. AI helps also in the development of vaccines and drugs (including drug repurposing) to obtain potential preventive and therapeutic agents for controlling the COVID-19 pandemic.
Topics: Artificial Intelligence; COVID-19; COVID-19 Vaccines; Drug Development; Humans; Pandemics; SARS-CoV-2; Viral Vaccines
PubMed: 35078755
DOI: 10.1016/j.jiph.2022.01.011 -
Frontiers in Medicine 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial dysfunction leading to particularly severe hypoxemia. We hypothesized that an impaired hypoxic pulmonary vasoconstriction aggravates hypoxemia. The objective of the study was to test the effect of two pulmonary vasoactive drugs on patient oxygenation. Observational, single-center, open-label study in one intensive care unit (ICU) of the Paris area, realized in April 2020. Eligible patients had coronavirus disease 2019 (COVID-19) and moderate to severe ARDS [arterial partial pressure of oxygen/fraction of inspired oxygen (PaO/FiO) <200 mmHg] despite conventional protective ventilation. Exclusion criteria included pulmonary artery hypertension defined by a pulmonary artery systolic pressure (PAPs) >45 mmHg. The assessment of oxygenation was based on PaO/FiO at (1) baseline, then after (2) 30 min of inhaled nitric oxide (iNO) 10 ppm alone, then (3) 30 min combination of iNO + almitrine infusion 8 μg/kg/min, then (4) 30 min of almitrine infusion alone. Among 20 patients requiring mechanical ventilation during the study period, 12 met the inclusion criteria. Baseline PaO/FiO was 146 ± 48 mmHg. When iNO was combined with almitrine, PaO/FiO rose to 255 ± 90 mmHg (+80 ± 49%, = 0.005), also after almitrine alone: 238 ± 98 mmHg (+67 ± 75%, = 0.02), but not after iNO alone: 185 ± 73 mmHg (+30 ± 5%, = 0.49). No adverse events related to almitrine infusion or iNO was observed. Combining iNO and infused almitrine improved the short-term oxygenation in patients with COVID-19-related ARDS. This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients.
PubMed: 34277653
DOI: 10.3389/fmed.2021.655763 -
World Journal of Clinical Cases May 2021Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus...
BACKGROUND
Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus disease 2019 (COVID-19) patients. It has been hypothesized that an increased pulmonary blood flow associated with an impairment of hypoxic pulmonary vasoconstriction is responsible for an intrapulmonary shunt. COVID-19 may lead to refractory hypoxemia (PaO/FiO ratio below 100 mmHg) despite mechanical ventilation and prone positioning. We hypothesized that the use of a pulmonary vasoconstrictor may help decrease the shunt and thus enhance oxygenation.
CASE SUMMARY
We report our experience with three patients with refractory hypoxemia treated with almitrine to enhance oxygenation. Low dose almitrine (Vectarion; Servier, Suresnes, France) was started at an infusion rate of 4 μg × kg/min on a central line. The PaO/FiO ratio and total respiratory system compliance during almitrine infusion were measured. For the three patients, the PaO/FiO ratio time-course showed a dramatic increase whereas total respiratory system compliance was unchanged. The three patients were discharged from the intensive care unit. The intensive care unit length of stay for patient 1, patient 2 and patient 3 was 30 d, 32 d and 31 d, respectively. Weaning from mechanical ventilation was performed 13 d, 18 d and 15 d after almitrine infusion for patient 1, 2 and 3, respectively. We found no deleterious effects on the right ventricular function, which was similar to previous studies on almitrine safety.
CONCLUSION
Almitrine may be effective and safe to enhance oxygenation in coronavirus disease 2019 patients. Further controlled studies are required.
PubMed: 34002149
DOI: 10.12998/wjcc.v9.i14.3385 -
Saudi Journal of Anaesthesia 2021
PubMed: 33824652
DOI: 10.4103/sja.SJA_782_20 -
Biochemical Pharmacology Jan 2021The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause... (Review)
Review
The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%. Unfortunately, a drug or vaccine is yet to be discovered to treat COVID-19. Thus, repurposing of existing cancer drugs will be a novel approach in treating COVID-19 patients. These drugs target viral replication cycle, viral entry and translocation to the nucleus. Some can enhance innate antiviral immune response as well. Hence this review focuses on comprehensive list of 22 drugs that work against COVID-19 infection. These drugs include fingolimod, colchicine, N4-hydroxycytidine, remdesivir, methylprednisone, oseltamivir, icatibant, perphanizine, viracept, emetine, homoharringtonine, aloxistatin, ribavirin, valrubicin, famotidine, almitrine, amprenavir, hesperidin, biorobin, cromolyn sodium, and antibodies- tocilzumab and sarilumab. Also, we provide a list of 31 drugs that are predicted to function against SARS-CoV-2 infection. In summary, we provide succinct overview of various therapeutic modalities. Among these 53 drugs, based on various clinical trials and literature, remdesivir, nelfinavir, methylpredinosolone, colchicine, famotidine and emetine may be used for COVID-19. SIGNIFICANCE: It is of utmost important priority to develop novel therapies for COVID-19. Since the effect of SARS-CoV-2 is so severe, slowing the spread of diseases will help the health care system, especially the number of visits to Intensive Care Unit (ICU) of any country. Several clinical trials are in works around the globe. Moreover, NCI developed a recent and robust response to COVID-19 pandemic. One of the NCI's goals is to screen cancer related drugs for identification of new therapies for COVID-19. https://www.cancer.gov/news-events/cancer-currents-blog/2020/covid-19-cancer-nci-response?cid=eb_govdel.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Drug Repositioning; Humans; SARS-CoV-2; Treatment Outcome; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33191206
DOI: 10.1016/j.bcp.2020.114296 -
Critical Care Medicine Feb 2021
Topics: Almitrine; COVID-19; Humans; Pharmaceutical Preparations; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2
PubMed: 33186137
DOI: 10.1097/CCM.0000000000004765 -
Annals of Intensive Care Nov 2020In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with...
BACKGROUND
In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients.
METHODS
We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 μg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO/FiO ratio).
RESULTS
Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO/FiO ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning.
CONCLUSION
In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.
PubMed: 33150525
DOI: 10.1186/s13613-020-00769-2 -
Critical Care Medicine Feb 2021Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may... (Clinical Trial)
Clinical Trial Observational Study
OBJECTIVES
Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome.
DESIGN
Single-center retrospective observational study.
SETTING
ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020.
PATIENTS
Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events.
INTERVENTIONS
Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 μg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion.
MEASUREMENTS AND MAIN RESULTS
A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale.
CONCLUSIONS
Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.
Topics: Almitrine; COVID-19; Critical Care; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; COVID-19 Drug Treatment
PubMed: 33093279
DOI: 10.1097/CCM.0000000000004711 -
JACC. Case Reports Jul 2020Coronavirus disease-19 (COVID-19)-related severe acute respiratory distress syndrome can lead to acute cor pulmonale. We report a case of acute cor pulmonale secondary...
Coronavirus disease-19 (COVID-19)-related severe acute respiratory distress syndrome can lead to acute cor pulmonale. We report a case of acute cor pulmonale secondary to severe COVID-19 acute respiratory distress syndrome diagnosed with transesophageal echocardiography. Almitrine infusion allowed rapid enhancement of right ventricular function as well as improvement in oxygenation. ().
PubMed: 32835274
DOI: 10.1016/j.jaccas.2020.06.011