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1.
BMC Pulm Med ; 21(1): 371, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526622

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms. METHODS: Rat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting. RESULTS: It showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1. CONCLUSION: It indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Pulmonary Disease, Chronic Obstructive/drug therapy , Saponins/pharmacology , Triterpenes/pharmacology , Animals , China , Inflammation/prevention & control , Lung/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein , Pulmonary Disease, Chronic Obstructive/pathology , Rats , Rats, Wistar , Smoking
2.
Curr Opin Pulm Med ; 28(2): 76-83, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1483670

ABSTRACT

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and COVID-19 have many potentially negative interrelationships, which may influence the course of infection and clinical outcomes. The aim of this review is to provide clinicians with an up-to-date perspective of the complex interactions between COPD and COVID-19. RECENT FINDINGS: We consider mechanisms that could increase SARS-CoV-2 infection susceptibility in COPD, including increased ACE2 expression, reduced antiviral defence and dysfunctional immunity. We review evidence that COPD is associated with worse clinical outcomes from COVID-19 in analyses that have adjusted for confounding factors, and describe the mechanisms responsible. We discuss the use of inhaled corticosteroids in the context of susceptibility to COVID-19, and consider the impact of COVID-19 on the usual care of COPD patients. SUMMARY: The current review highlights the evidence that COPD patients have worse outcomes from COVID-19, and the multiple mechanisms responsible.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Adrenal Cortex Hormones/therapeutic use , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2
3.
Int J Chron Obstruct Pulmon Dis ; 16: 2687-2695, 2021.
Article in English | MEDLINE | ID: covidwho-1456164

ABSTRACT

COVID-19 has affected millions of patients, caregivers, and clinicians around the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads via droplets and close contact from person to person, and there has been an increased concern regarding aerosol drug delivery due to the potential aerosolizing of viral particles. To date, little focus has been given to aerosol drug delivery to patients with COVID-19 treated at home to minimize their hospital utilization. Since most hospitals were stressed with multiple admissions and experienced restricted healthcare resources in the era of COVID-19 pandemic, treating patients with COPD at home became essential to minimize their hospital utilization. However, guidance on how to deliver aerosolized medications safely and effectively to this patient population treated at home is still lacking. In this paper, we provide some strategies and rationales for device and interface selection, delivery technique, and infection control for patients with COPD who are being treated at home in the era of COVID-19 and beyond.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Pulmonary Disease, Chronic Obstructive , Humans , Pandemics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , SARS-CoV-2
4.
Expert Rev Respir Med ; 15(12): 1605-1612, 2021 12.
Article in English | MEDLINE | ID: covidwho-1434304

ABSTRACT

BACKGROUND: During the pandemic, there have been disruptions to how patients seek care. RESEARCH DESIGN AND METHODS: To investigate monthly prescription claims for asthma and chronic obstructive pulmonary disease (COPD) medicines during the first UK wave, interrupted time series (ITS) analysis was used. A national cohort of community patients' data were examined. RESULTS: Descriptive statistics show salbutamol, aminophylline, ipratropium, and theophylline remain below pre-pandemic levels.Montelukast showed pre-pandemic monthly increase (Est. 67,151 doses, P = 0.05, 95% CI: 1011, 133,291), followed by a jump of 1.6 million doses at March , followed by monthly declines (Est. -112,098 doses, P = 0.216, 95% CI: -293,499, 69,303).Before the pandemic, tiotropium, salbutamol, aminophylline, and ipratropium (P = 0.003) show monthly declines but theophylline and beclometasone showed increases. In March , salbutamol (P = 0.033) and ipratropium (P = 0.001) show a significant jump. After March , ipratropium continues with a downward trajectory (P = 0.001), with a generalized negative trend for all other agents. Salbutamol confidence bounds become negative after March 2020. Some brands were unavailable. CONCLUSIONS: An 'unmet' medical gap is identified. While it is essential to understand the underlying reasons, urgent action needs to be taken to reassess patients and ensure continuity of care.PLAIN LANGUAGE SUMMARIES (PLS)Asthma and chronic obstructive pulmonary disease (COPD) are long-term lung conditions, affecting 6 million & 1.2 million people respectively and causing breathing difficulties. Sufferers are at a higher risk of chest infections including the coronavirus. Regular use of prescribed medication stabilizes these conditions and prevents them from getting worse. It is common to be prescribed a combination of five to eight oral and inhaled medications.We investigated the impact of the pandemic on the dispensing of these specific medicines across England during the first wave. The English Prescribing Dataset was checked from January 2019 to February 2020 (14 months before the pandemic) and March to October 2020 (8 months after its onset).We find that since March 2020, salbutamol, aminophylline, ipratropium, and theophylline have not returned to their pre-pandemic levels. However, for all agents, there is great variability. Further analysis suggests these trends are not reversing, suggesting that people have not been using their medication as anticipated for 8 months, which is concerning.As a consequence of this work, we recommend that doctors specifically call these patients and discuss their health as a matter of urgency, we encourage patients to continue to take their medication. We advise policy changes to waive the NHS prescription levy for asthma and COPD medication and we seek more granular data for further harm quantification. There are several strengths and weaknesses to our analysis, and we need to conduct more studies to ask patients about their experiences.


Subject(s)
Asthma , COVID-19 , Pulmonary Disease, Chronic Obstructive , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Bronchodilator Agents/adverse effects , Drug Prescriptions , England/epidemiology , Humans , Ipratropium/therapeutic use , Pandemics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2
5.
Rev Esp Quimioter ; 34(5): 429-440, 2021 Oct.
Article in Spanish | MEDLINE | ID: covidwho-1417555

ABSTRACT

COPD (chronic obstructive pulmonary disease) includes patients with chronic bronchitis and / or emphysema who have in common the presence of a chronic and progressive airflow obstruction, with symptoms of dyspnea and whose natural history is modified by acute episodes of exacerbations. Exacerbation (EACOPD) is defined as an acute episode of clinical instability characterized by a sustained worsening of respiratory symptoms. It is necessary to distinguish a new EACOPD from a previous treatment failure or a relapse. EACOPD become more frequent and intense over time, deteriorating lung function and quality of life. The diagnosis of EACOPD consists of 3 essential steps: a) differential diagnosis; b) establish the severity, and c) identify its etiology. The main cause of exacerbations is infection, both bacterial and viral. Antibiotics are especially indicated in severe EACOPD and the presence of purulent sputum. Beta-lactams (amoxicillin-clavulanate and cefditoren) and fluoroquinolones (levofloxacin) are the most widely used antimicrobials. This review updates the problem of acute exacerbation with infectious origin from the perspective of etiology, antimicrobial resistance, microbiological studies, risk stratification, and antimicrobial management. The risk, prognosis and characteristics of COPD patients who develop COVID19 are analyzed.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Anti-Bacterial Agents/therapeutic use , Disease Progression , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , SARS-CoV-2
6.
Lancet Respir Med ; 9(8): 909-923, 2021 08.
Article in English | MEDLINE | ID: covidwho-1411740

ABSTRACT

BACKGROUND: Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population. The aim of this study was to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19. METHODS: In this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England's database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19. All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study. With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19. FINDINGS: Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0·2%) were admitted to hospital with COVID-19, 1542 (<0·1%) were admitted to ICU, and 5956 (0·1%) died. People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease [COPD] hazard ratio [HR] 1·54 [95% CI 1·45-1·63], asthma 1·18 [1·13-1·24], severe asthma 1·29 [1·22-1·37; people on three or more current asthma medications], bronchiectasis 1·34 [1·20-1·50], sarcoidosis 1·36 [1·10-1·68], extrinsic allergic alveolitis 1·35 [0·82-2·21], idiopathic pulmonary fibrosis 1·59 [1·30-1·95], other interstitial lung disease 1·66 [1·30-2·12], and lung cancer 2·24 [1·89-2·65]) and death (COPD 1·54 [1·42-1·67], asthma 0·99 [0·91-1·07], severe asthma 1·08 [0·98-1·19], bronchiectasis 1·12 [0·94-1·33], sarcoidosis 1·41 [0·99-1·99), extrinsic allergic alveolitis 1·56 [0·78-3·13], idiopathic pulmonary fibrosis 1·47 [1·12-1·92], other interstitial lung disease 2·05 [1·49-2·81], and lung cancer 1·77 [1·37-2·29]) due to COVID-19 compared with those without these diseases. Admission to ICU was rare, but the HR for people with asthma was 1·08 (0·93-1·25) and severe asthma was 1·30 (1·08-1·58). In a post-hoc analysis, relative risks of severe COVID-19 in people with respiratory disease were similar before and after shielding was introduced on March 23, 2020. In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1·13 (1·03-1·23) for hospitalisation, 1·63 (1·18-2·24) for ICU admission, and 1·15 (1·01-1·31) for death. INTERPRETATION: The risk of severe COVID-19 in people with asthma is relatively small. People with COPD and interstitial lung disease appear to have a modestly increased risk of severe disease, but their risk of death from COVID-19 at the height of the epidemic was mostly far lower than the ordinary risk of death from any cause. Use of inhaled steroids might be associated with a modestly increased risk of severe COVID-19. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre and the Wellcome Trust.


Subject(s)
Adrenal Cortex Hormones , COVID-19 , Pulmonary Disease, Chronic Obstructive , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19 Testing , Comorbidity , England/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Mortality , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Assessment , SARS-CoV-2/isolation & purification , Social Class
7.
Eur J Med Chem ; 225: 113818, 2021 Dec 05.
Article in English | MEDLINE | ID: covidwho-1385491

ABSTRACT

Cathepsin C, an important lysosomal cysteine protease, mediates the maturation process of neutrophil serine proteases, and participates in the inflammation and immune regulation process associated with polymorphonuclear neutrophils. Therefore, cathepsin C is considered to be an attractive target for treating inflammatory diseases. With INS1007 (trade name: brensocatib) being granted a breakthrough drug designation by FDA for the treatment of Adult Non-cystic Fibrosis Bronchiectasis and Coronavirus Disease 2019, the development of cathepsin C inhibitor will attract attentions from medicinal chemists in the future soon. Here, we summarized the research results of cathepsin C as a therapeutic target, focusing on the development of cathepsin C inhibitor, and provided guidance and reference opinions for the upcoming development boom of cathepsin C inhibitor.


Subject(s)
Anti-Inflammatory Agents/chemistry , Cathepsin C/antagonists & inhibitors , Drug Discovery , Protease Inhibitors/chemistry , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Cathepsin C/genetics , Cathepsin C/metabolism , Humans , Papillon-Lefevre Disease/genetics , Papillon-Lefevre Disease/pathology , Protease Inhibitors/metabolism , Protease Inhibitors/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , SARS-CoV-2/isolation & purification , Serine Endopeptidases/metabolism
8.
BMC Pulm Med ; 21(1): 278, 2021 Aug 31.
Article in English | MEDLINE | ID: covidwho-1381257

ABSTRACT

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report. CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive. CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Delayed Diagnosis , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Asthma/complications , Asthma/drug therapy , Asthma/pathology , Bronchoalveolar Lavage , COVID-19/complications , COVID-19/therapy , Fatal Outcome , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Reverse Transcriptase Polymerase Chain Reaction
9.
BMJ Open ; 11(8): e053446, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1376513

ABSTRACT

INTRODUCTION: Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (ß)-blockers. There is observational evidence that cardioselective ß-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective ß-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective ß-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity. METHODS AND ANALYSES: This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV1) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months. ETHICS AND DISSEMINATION: The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital. TRIAL REGISTRATION NUMBERS: NCT03917914; CTRI/2020/08/027322.


Subject(s)
Bisoprolol , Pulmonary Disease, Chronic Obstructive , Bisoprolol/therapeutic use , Disease Progression , Double-Blind Method , Forced Expiratory Volume , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic
10.
Int J Mol Sci ; 22(17)2021 Aug 24.
Article in English | MEDLINE | ID: covidwho-1374422

ABSTRACT

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Subject(s)
Airway Remodeling/drug effects , Lung/pathology , Nerve Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Asthma/drug therapy , Asthma/pathology , COVID-19/drug therapy , COVID-19/pathology , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/pathology , Lung/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Molecular Targeted Therapy/methods , Nerve Growth Factor/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology
11.
Respir Investig ; 59(6): 871-875, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1364443

ABSTRACT

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.


Subject(s)
Lung/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Radiographic Image Enhancement/methods , Radiography, Thoracic/methods , Aged , Asthma/diagnosis , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Drug Combinations , Fluticasone/therapeutic use , Formoterol Fumarate/therapeutic use , Glycopyrrolate/analogs & derivatives , Glycopyrrolate/therapeutic use , Humans , Indans/therapeutic use , Lung/physiology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/therapeutic use , Spirometry , Tiotropium Bromide/therapeutic use , Treatment Outcome
13.
BMJ Open ; 11(8): e049515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-1346064

ABSTRACT

INTRODUCTION: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate. METHODS AND ANALYSIS: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission. ETHICS AND DISSEMINATION: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04682899.


Subject(s)
Bacterial Infections , Pulmonary Disease, Chronic Obstructive , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Humans , Inpatients , Multicenter Studies as Topic , Procalcitonin , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic
15.
PLoS One ; 16(6): e0252576, 2021.
Article in English | MEDLINE | ID: covidwho-1256043

ABSTRACT

Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD. This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020. Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes. Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease. Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033). Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80). Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49). In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system. These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/pharmacology , Adrenergic beta-2 Receptor Agonists/adverse effects , Adult , Aged , COVID-19/complications , COVID-19 Testing , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Muscarinic Antagonists/therapeutic use , Nebulizers and Vaporizers , Pandemics , Pulmonary Disease, Chronic Obstructive/complications , Registries , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
16.
Neurologist ; 26(3): 108-111, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1214713

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulable state, increasing the risk for ischemic stroke. In select cases, patients are already on anticoagulation therapy. Such examples highlight the severity of COVID-19's hyperthrombotic state, and raise questions regarding optimal stroke prevention in these patients. CASE REPORT: An 84-year-ool male with past medical history of chronic obstructive pulmonary disease, hypertension, and paroxysmal atrial fibrillation was admitted for respiratory failure secondary to COVID-19 pneumonia. He was continued on his home apixaban 5 mg twice daily. On day 2 of admission, he developed a new aphasia, and right-sided facial droop. Computed tomography (CT) head was unrevealing. CT angiography did not show large vessel occlusion. CT perfusion demonstrated a left middle cerebral artery ischemic penumbra, without core. He was not eligible for thrombolysis or thrombectomy interventions. Later CT head confirmed L middle cerebral artery infarct. The patient's D-dimer was 1,184 ng/mL on day 1 of admission, and increased to 111,574 by day 4. His hypoxia worsened, requiring intubation and transfer to the ICU. He experienced further clinical decline and eventual demise. CONCLUSION: Ischemic stroke in anticoagulated patients with COVID-19 has been previously reported. Such cases emphasize the severity of the coronavirus virus associated hypercoagulable state. A majority of reported cases have occurred in patients continuing their ambulatory therapy. Overall, such cases are likely underreported. There are current trials comparing therapeutic versus prophylactic dose anticoagulation in patients with COVID-19. There are no studies specifically addressing anticoagulation agent failure in these patients. Further research is required this area to determine the optimal therapy for patients with COVID-19.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Ischemic Stroke/etiology , Aged, 80 and over , Atrial Fibrillation/drug therapy , Fatal Outcome , Humans , Hypertension/drug therapy , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pyrazoles/administration & dosage , Pyridones/administration & dosage
18.
Arterioscler Thromb Vasc Biol ; 41(3): e175-e182, 2021 03.
Article in English | MEDLINE | ID: covidwho-1189968

ABSTRACT

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pandemics , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/mortality , Child , Child, Preschool , Cohort Studies , Diabetes Complications/drug therapy , Diabetes Complications/mortality , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Infant , Infant, Newborn , Male , Middle Aged , Pneumonia/drug therapy , Pneumonia/mortality , Propensity Score , Proportional Hazards Models , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/mortality , Republic of Korea/epidemiology , Retrospective Studies , Young Adult
20.
Am J Health Syst Pharm ; 78(13): 1184-1194, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1169635

ABSTRACT

PURPOSE: This article reviews the efficacy and safety of revefenacin, the first once-daily, long-acting muscarinic antagonist, when delivered via a standard jet nebulizer in patients with chronic obstructive pulmonary disease (COPD). SUMMARY: Revefenacin 175 µg is indicated for the maintenance treatment of patients with moderate to very severe COPD. Preclinical studies showed that revefenacin is a potent and selective antagonist with similar affinity for the different subtypes of muscarinic receptors (M1-M5). Furthermore, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose dependent and lasted longer than 24 hours, demonstrating a long duration of action. In phase 2 and 3 trials, treatment with revefenacin was demonstrated to result in statistical improvements in pulmonary function (≥100 mL, P < 0.05) vs placebo, including among patients with markers of more severe disease and those who received concomitant long-acting ß-agonists or long-acting ß-agonists together with inhaled corticosteroids. Revefenacin was also demonstrated to have efficacy similar to that of tiotropium. The clinical trial findings indicated no significant difference between revefenacin and tiotropium with regard to rates of adverse events. Overall, revefenacin was well tolerated, with COPD worsening/exacerbation, dyspnea, headache, and cough among the most common adverse events noted in the clinical trials. CONCLUSIONS: Revefenacin treatment delivered via nebulization led to improvements in lung function in patients with COPD. It was also generally well tolerated, with no major safety concerns. Revefenacin provides a viable treatment option for patients with COPD and may be a suitable alternative for those with conditions that may impair proper use of traditional handheld inhalers.


Subject(s)
Muscarinic Antagonists , Pulmonary Disease, Chronic Obstructive , Administration, Inhalation , Benzamides , Bronchodilator Agents/therapeutic use , Carbamates/therapeutic use , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy
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