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Cell Host & Microbe Aug 2023The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines...
The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines may be contributing to this rise. While T cells are key in controlling and preventing disease, nearly all knowledge relates to antigens in aP vaccines. A whole-genome mapping of human BP-specific CD4+ T cell responses was performed in healthy vaccinated adults and revealed unexpected broad reactivity to hundreds of antigens. The overall pattern and magnitude of T cell responses to aP and non-aP vaccine antigens are similar regardless of childhood vaccination, suggesting that asymptomatic infections drive the pattern of T cell reactivity in adults. Lastly, lack of Th1/Th2 polarization to non-aP vaccine antigens suggests these antigens have the potential to counteract aP vaccination Th2 bias. These findings enhance our insights into human T cell responses to BP and identify potential targets for next-generation pertussis vaccines.
Topics: Adult; Humans; Bordetella pertussis; Whooping Cough; Immunization, Secondary; Pertussis Vaccine; Vaccination
PubMed: 37490913
DOI: 10.1016/j.chom.2023.06.015 -
Respiratory Research Nov 2023Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by...
BACKGROUND
Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID.
METHODS
Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.
RESULTS
At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan-Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months.
CONCLUSIONS
In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Sputum; SARS-CoV-2; Cohort Studies; Japan; Cough
PubMed: 37964338
DOI: 10.1186/s12931-023-02591-3 -
European Journal of Clinical... Sep 2023Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g.,...
Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g., weight loss, fatigue, fever), chronic productive cough, chest discomfort, and occasional haemoptysis, which are similar to the manifestations of pulmonary tuberculosis (PTB) and are often misdiagnosed as PTB. Considering the striking similarities between CPA and PTB in clinical manifestations and imaging features, more specific microbiological and serological detections are needed for a definitive diagnosis. This study aimed to explore the clinical characteristics of CPA in TB as well as the diagnostic significance of Aspergillus-specific IgG and Aspergillus-specific IgM.A total of 140 patients diagnosed with TB by culture between December 2017 and February 2019 were included. Enrolled patients were categorized into two groups (CPA group and non-CPA group) according to CPA diagnostic criteria. All collected specimens were subjected to Aspergillus-specific IgG and IgM detection testing.The median concentration of Aspergillus-specific IgG in the CPA group (211.04 AU/ml) was significantly higher than that in the non-CPA group (77.88 AU/ml) (Z value - 6.397, P < 0.001). The sensitivity and specificity of Aspergillus-specific IgG for CPA diagnosis were 81.82% and 72.97%, respectively. In the chronic cavitary pulmonary aspergillosis (CCPA) group, the IgG positivity rate (≥ 120 AU/ml) was 96.2%, which was 21.4% in the non-CCPA patients (P < 0.001).The detection of Aspergillus-specific IgG serological changes is feasible and facilitates reliable differentiation between Aspergillus and Mycobacterium tuberculosis infection. However, Aspergillus-specific IgM has limited diagnostic value, with unsatisfactory sensitivity results.
Topics: Humans; Immunoglobulin G; Chronic Disease; Pulmonary Aspergillosis; Aspergillus; Tuberculosis; Immunoglobulin M; Tuberculosis, Pulmonary; Persistent Infection; Antibodies, Fungal
PubMed: 37453946
DOI: 10.1007/s10096-023-04637-2 -
Frontiers in Medicine 2024Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory condition characterized by symptoms of dyspnea, cough, and sputum production. We review... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory condition characterized by symptoms of dyspnea, cough, and sputum production. We review sex-differences in disease mechanisms, structure-function-symptom relationships, responses to therapies, and clinical outcomes in COPD with a specific focus on dyspnea. Females with COPD experience greater dyspnea and higher morbidity compared to males. Imaging studies using chest computed tomography scans have demonstrated that females with COPD tend to have smaller airways than males as well as a lower burden of emphysema. Sex-differences in lung and airway structure lead to critical respiratory mechanical constraints during exercise at a lower absolute ventilation in females compared to males, which is largely explained by sex differences in maximum ventilatory capacity. Females experience similar benefit with respect to inhaled COPD therapies, pulmonary rehabilitation, and smoking cessation compared to males. Ongoing re-assessment of potential sex-differences in COPD may offer insights into the evolution of patterns of care and clinical outcomes in COPD patients over time.
PubMed: 38572156
DOI: 10.3389/fmed.2024.1289259 -
Journal of Ethnopharmacology Jan 2024Portulaca oleracea L. (PO), popularly known as purslane, has been documented in ethnopharmacology in various countries and regions. Traditional application records... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Portulaca oleracea L. (PO), popularly known as purslane, has been documented in ethnopharmacology in various countries and regions. Traditional application records indicated that PO might be used extensively to treat the common cold, dysentery, urinary tract infections, coughing, eye infections, skin problems, gynecological diseases, and pediatric illnesses.
AIM OF THE REVIEW
This paper includes a systematic review of the traditional usage, phytochemicals, pharmacological activity, and potential uses of PO to provide an overview of the research for further exploitation of PO resources.
MATERIALS AND METHODS
This article uses "Portulaca oleracea L." and "purslane" as the keywords and collects relevant information on PO from different databases, including PubMed, Web of Science, Springer, Science Direct, ACS, Wiley, CNKI, Baidu Scholar, Google Scholar, and ancient meteria medica.
RESULTS
PO is a member of the Portulacaceae family and is grown worldwide. Traditional Chinese medicine believes that purslane has the effect of improving eyesight, eliminating evil qi, quenching thirst, purgation, diuresis, hemostasis, regulating qi, promoting hair growth, detoxifying, and avoiding epidemic qi. Recent phytochemical investigations have shown that PO is a rich source of flavonoids, homoisoflavonoids, alkaloids, organic acids, esters, lignans, terpenoids, catecholamines, sterols, and cerebrosides. The purslane extracts or compounds have exhibited numerous biological activities such as anti-inflammatory, immunomodulatory, antimicrobial, antiviral, antioxidant, anticancer, renoprotective, hepatoprotective, gastroprotective, metabolic, muscle relaxant, anti-asthmatic and anti-osteoporosis properties. The significant omega-3 fatty acids, vital amino acids, minerals, and vitamins found in purslane also provide nutritional benefits. Purslane as a food/feed additive in the food industry and animal husbandry has caused concern. Its global wide distribution and tolerance to abiotic stress characteristics make it in the future sustainable development of agriculture a certain position.
CONCLUSIONS
Based on traditional usage, phytochemicals, and pharmacological activity, PO is a potential medicinal and edible plant with diverse pharmacological effects. Due to purslane's various advantages, it may have vast application potential in the food and pharmaceutical industries and animal husbandry.
Topics: Animals; Child; Humans; Ethnopharmacology; Medicine, Chinese Traditional; Phytochemicals; Plant Extracts; Portulaca
PubMed: 37739100
DOI: 10.1016/j.jep.2023.117211 -
The Journal of International Medical... Aug 2023Cough is a frequent symptom accompanied by lung cancer. More potent antitussive treatment for this complex and distressing symptom is required, but anti-cancer...
Cough is a frequent symptom accompanied by lung cancer. More potent antitussive treatment for this complex and distressing symptom is required, but anti-cancer chemotherapy cannot fully manage the cough. Inhibition of vagal nerves might control coughing in patients with troublesome lung cancer-related cough and P2X inhibitory therapy may be useful for targeting neuronal function. We report the case of a woman in her late 70s who never smoked and had advanced lung cancer. She visited our hospital complaining of serious deterioration of a non-productive cough. She was diagnosed with relapse of lung cancer, but she requested 2-week anti-tussive therapy before second-line chemotherapy. Gefapixant (P2X antagonist) add-on at a dose of 90 mg/day (45 mg twice daily as the usual dosage in Japan) improved her cough as indicated by an improvement in the visual analog scale for cough from 70 to 20 mm and in the Japanese version of the Leicester Cough Questionnaire from 8.2 to 16.3, despite a deterioration in lung cancer after 2 weeks. There are no current guidelines for cough accompanied by lung cancer; however, our findings suggest that P2X inhibition is a potent therapeutic option for lung cancer-related cough.
Topics: Humans; Female; Cough; Lung Neoplasms; Sulfonamides; Antitussive Agents
PubMed: 37641866
DOI: 10.1177/03000605231194890 -
BMJ Open Dec 2023This study examined whether the US President's Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and...
OBJECTIVES
This study examined whether the US President's Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and child health in low-income and middle-income countries (LMICs). The results of previous research on the question of PEPFAR health spillovers have been inconsistent. This study, using a large, multicountry panel data set of 157 LMICs including 90 recipient countries, adds to the literature.
DESIGN
Seven indicators including child and maternal mortality, several child vaccination rates and anaemia among childbearing-age women are important population health indicators. Panel data and difference-in-differences estimators (DID) were used to estimate the impact of the PEPFAR programme from inception in 2004 to 2018 using a comparison group of 67 LMICs. Several different models of baseline (2004) covariates were used to help balance the comparison and treatment groups. Staggered DID was used to estimate impacts since all countries did not start receiving aid at PEPFAR's inception.
SETTING
All 157 LMICs from 1990 to 2018.
PARTICIPANTS
90 LMICs receiving PEPFAR aid and cohorts of those countries, including those required to submit annual country operational plans (COP), other recipient countries (non-COP), and three groupings of countries based on cumulative amount of per capita aid received (high, medium, low).
INTERVENTIONS
PEPFAR aid to combat the HIV epidemic.
PRIMARY OUTCOME MEASURES
Maternal mortality and child mortality rates, vaccination rates to protect children for diphtheria, whooping cough and tetanus, measles, HepB3, and tetanus, and prevalence of anaemia in women of childbearing age.
RESULTS
Across PEPFAR recipient countries, large, favourable PEPFAR health effects were found for rates of childhood immunisation, child mortality and maternal mortality. These beneficial health effects were large and significant in all segments of PEPFAR recipient countries studied. We also found significant and favourable programme effects on the prevalence of anaemia in women of childbearing age in PEPFAR recipient countries receiving the most intensive financial support from the PEPFAR programme. Other recipient countries did not demonstrate significant effects on anaemia.
CONCLUSIONS
This study demonstrated that important health indicators, beyond HIV, have been consistently and favourably influenced by PEPFAR presence. Child and maternal mortality have been substantially reduced, and childhood immunisation rates increased. We also found no evidence of 'crowding out' or negative spillovers in these resource-poor countries. These findings add to the body of evidence that PEPFAR has had favourable health effects beyond HIV. The implications of these findings are that foreign aid for health in one area may have favourable health effects in other areas in recipient countries. More research is needed on the influence of the mechanisms at work that create these spillover health effects of PEPFAR.
Topics: Child; Humans; Female; HIV Infections; Child Health; Tetanus; International Cooperation; Anemia
PubMed: 38135335
DOI: 10.1136/bmjopen-2022-070221 -
Postgraduate Medicine Nov 2023Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report, the scientific committee concluded that the use of long-acting β-agonist/inhaled corticosteroids (LABA/ICS) is not encouraged in patients with COPD. However, current prescribing patterns reveal significant use of LABA/ICS. In this paper, the evidence behind the current practice and the latest treatment recommendations is reviewed. We compare the efficacy and safety of combination therapy with long-acting muscarinic antagonist (LAMA) and LABA vs LABA/ICS and note that LAMA/LABA combinations have reduced the annual rate of moderate/severe exacerbations, delayed the time to first exacerbation, and increased post-dose FEV vs ICS-based regimens. The GOLD 2023 report recommends treatment with LABA and LAMA combination (preferably as a single inhaler) in patients with persistent dyspnea, with initiation of ICS in patients based on the symptoms (dyspnea and exercise intolerance as indicated by modified Medical Research Council [mMRC] score ≥ 2 and COPD Assessment Test [CAT™] > 20), blood eosinophil count (≥ 300 cells/µL), and exacerbation history (history of hospitalizations for exacerbations of COPD and ≥ 2 moderate exacerbations per year despite appropriate long-acting bronchodilator maintenance therapy). We describe practical recommendations for primary care physicians to optimize therapy for their patients and prevent overuse of ICS-based regimens. We advocate adherence to current recommendations and a greater focus on effective treatments to successfully control symptoms, minimize exacerbation risk, preserve lung function, maximize patient outcomes, and reduce the burden of drug-related adverse events.
Topics: Humans; Adrenergic beta-2 Receptor Agonists; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Administration, Inhalation; Drug Therapy, Combination; Adrenal Cortex Hormones; Dyspnea; Bronchodilator Agents
PubMed: 38032494
DOI: 10.1080/00325481.2023.2284650 -
BioDrugs : Clinical Immunotherapeutics,... May 2024The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for...
BACKGROUND
The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs.
OBJECTIVE
The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database.
METHODS
We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3).
RESULTS
Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab.
CONCLUSIONS
The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.
Topics: Humans; Asthma; Pharmacovigilance; World Health Organization; Anti-Asthmatic Agents; Female; Male; Antibodies, Monoclonal, Humanized; Adverse Drug Reaction Reporting Systems; Databases, Factual; Adult; Biological Therapy; Middle Aged; Aged; Omalizumab; Biological Products
PubMed: 38489062
DOI: 10.1007/s40259-024-00653-6 -
Current Drug Safety 2024Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as... (Review)
Review
INTRODUCTION
Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as an antipyretic to reduce fever and as an alternative to Non-steroidal anti-inflammatory drugs (NSAIDs) that are contraindicated in certain patients to relieve mild-moderate pain.
OBJECTIVE
This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products.
METHODS
To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms.
RESULTS
The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications.
CONCLUSION
When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.
Topics: Humans; Stevens-Johnson Syndrome; Drug Hypersensitivity Syndrome; Acute Generalized Exanthematous Pustulosis; Acetaminophen; Pain
PubMed: 37151075
DOI: 10.2174/1574886318666230505144014