Clinical Exacerbation Research Articles

Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn's disease.

Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). A post hoc analysis study. Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.

Associations between depression and anxiety index and frequency of acute exacerbation in chronic obstructive pulmonary disease.

Comorbidities of chronic obstructive pulmonary disease (COPD) influence clinical characteristics and prognosis. This study compared the clinical characteristics and exacerbation rate of COPD according to the presence of depression or anxiety. This study used data from The Korea COPD Subgroup Study (KOCOSS) cohort, a nationwide prospective cohort from 54 medical centers, between April 2012 and 2019. Depression and anxiety were diagnosed with the Beck Depression Inventory and Beck Anxiety Inventory. Negative binomial regression analysis was performed to analyze the frequency of exacerbations in depressed patients and anxiety. Differences in lung function trajectory according to presence of depression/anxiety were analyzed using a linear mixed model. In all, 2147 patients were enrolled. Depressed patients or anxiety had lower lung function, higher modified Medical Research Council (mMRC) grade, St. George Respiratory Questionnaire (SGRQ) score, and COPD assessment test score, and higher rates of exacerbation in the past year than those without depression/anxiety. Depressed patients had a higher frequency of moderate to severe exacerbations [Incidence Rate Ratio (IRR): 1.57, CI: 1.17-2.11, p = 0.002] and those with anxiety had higher frequencies of moderate to severe (IRR: 1.52, CI: 1.03-2.27, p = 0.038) and severe exacerbations (IRR: 2.13, CI: 1.09-4.15, p = 0.025) during 1-year follow-up compared to those without these comorbidities. The differences in the change in annual forced expiratory volume in 1 seconds (FEV1) over 3 years according to the presence of depression or anxiety were not statistically significant. Depressed and anxious patients showed increased respiratory symptoms and exacerbation rate as well as reduced health-related quality of life, whereas there were no significant differences in changes in lung function between groups with and without depression/anxiety.

Side‐by‐Side Comparative Study of a Moisturizer and Topical Tacrolimus for Treating Mild to Moderate Atopic Dermatitis: A Randomized Single‐Blinded Clinical Trial

The appropriate use of therapeutic moisturizers could reduce the need for more aggressive treatment in the management of atopic dermatitis (AD). We conducted a randomized, side‐by‐side, single‐blinded, comparative study in 41 mild to moderate AD patients to compare a moisturizer and topical tacrolimus for restoring skin barrier function and managing AD. A moisturizer was applied twice daily for 4 weeks to one side of the flexural areas (moisturizer group). Topical tacrolimus was applied on the other side of the tested area (tacrolimus group). Biophysical skin parameters were measured at baseline, week 2, and week 4. Clinical qualitative assessments were also conducted. Analysis of the trend from baseline to week 4 revealed that the hydration level was significantly increased in both groups (p < 0.01, respectively). No biophysical parameters were significantly different between the two groups. Differences in the modified Eczema Area and Severity Index scores between the baseline and week 4 were significantly higher in the tacrolimus group than those in the moisturizer group (p = 0.002). In the Investigator’s Global Assessment, a significantly larger proportion of patients in the tacrolimus group showed clinical improvement than that in the moisturizer group at week 4 (p = 0.027). Although topical tacrolimus was superior to the moisturizer in preventing the clinical exacerbation of AD, the moisturizer was not inferior to topical tacrolimus in restoring skin barrier function. Therefore, moisturizer is considered to play an essential role in maintenance therapy for AD. Physicians need to emphasize the benefits of moisturizers when educating their patients.

Self-Reported Insufficient Sleep Is Associated With Clinical and Inflammatory Features of Asthma: A Prospective Cohort Study

A few studies have explored the association between short sleep duration and worse asthma outcomes in patients with self-reported asthma; however, all of them were cross-sectional. To investigate the association between self-reported sleep duration and asthma-related clinical and inflammatory characteristics and whether sleep duration is associated with asthma exacerbations (AEs) in the following year. A prospective cohort study consecutively recruitedparticipants with asthma, who were classified into short (n= 58), normal (n= 380), and long (n= 84) sleep duration groups. We investigated the clinical and inflammatory characteristics and exacerbations within a 1-year follow-up. Patients with short sleep duration were older and had significantly lower total IgE and FeNO levels and higher airway inflammation, characterized by increased levels of IL-6 and TNF-α in sputum than those of patients with normal sleep duration. Furthermore, they had a significantly increased risk for poorly controlled asthma (adjusted odds ratio= 2.741; 95% CI, 1.379-5.447; P= .004) and moderate to severe AEs (adjusted incidence rate ratio= 1.798; 95% CI, 1.098-2.942; P= .020). Short sleep duration was associated with non-type 2 inflammation and is an independent risk factor for future AEs. Therefore, as a potentially treatable trait, sleep duration may have clinical implications for asthma management.

Pediatric asthma control in tertiary care setting using telemedicine during COVID-19 era.

During the coronavirus disease 2019 (COVID-19) pandemic, national measures have affected health care services. Children with asthma were a vulnerable population who were advised to avoid needless hospital visits. Telemedicine was utilized in this circumstance. However, data in Thailand is limited. This study aimed to evaluate asthma control in patients who were followed up by telemedicine compared with in-person visits at an outpatient clinic in Thailand's tertiary academic medical center. This was a retrospective study among pediatric patients with asthma who were followed up in the pediatric pulmonary and allergy clinic of Srinagarind Hospital from 1 January to 31 May 2021. We offered telemedicine (telephone visit) and in-person visits at the hospital by their willingness during this period. All patients were asked about asthma clinical control symptoms, medication compliance, exacerbation events, and hospital admissions by pediatric pulmonologists and allergists. Then, we decided to prescribe in controller medications. In the telemedicine groups, we used the postal service to deliver controller medicine to patients. Among 195 asthmatic children, 83 (42.56%) were followed up by telemedicine. Children who were followed up by telemedicine had more controlled symptoms than the in-person visit group [adjusted relative risk (aRR): 1.219; 95% confidence interval (CI): 1.062-1.400; P value =0.005]. In the in-person visit group, children had more asthma exacerbation events than telemedicine (5 vs. 0, respectively, P value =0.073). During the COVID-19 pandemic, telemedicine follow-up in asthmatic children resulted in well-controlled symptoms and few asthma exacerbation events.

Complementary Treatment of Allergic Conjunctivitis: The Role of Quercetin

Quercetin offers interesting beneficial options in clinical practice by providing anti-allergic and anti-inflammatory activities. This article reports and discusses the effectiveness of oral administration of quercetin Phytosome™ in adults presenting allergic conjunctivitis. The analysis was conducted by evaluating both subjective symptoms reported by individuals; and objective analysis of tear film instability due to allergic conjunctivitis inflammation using a non-invasive and computerized evaluation model. Outcomes provided evidence that quercetin Phytosome may significantly be a natural effort to avoid clinical worsening when supplemented as add-on to continuous anti-histaminic treatment and also prevent clinical exacerbations.

Clinical Emergence of Low-flow Vascular Malformations After Vaccination Against SARS-CoV-2: A Case Series

Studies have demonstrated that all 3 of the FDA-approved COVID-19 vaccines (Pfizer-BioNTech, Moderna, and Johnson & Johnson) are effective at reducing SARS-CoV-2-related hospitalizations, severe disease, and death. While these vaccinations have demonstrated a compelling safety profile, no discussion regarding the impact of COVID-19 vaccination on the exacerbation of slow-flow vascular malformations (SFVMs) has been had. We present the first case series of 3 consecutive patients who demonstrated clinical emergence or exacerbation of venous malformation status-post COVID-19 vaccination. As trauma, infection, and systemic inflammation can contribute to exacerbation of these vascular anomalies, COVID-19 vaccination may contribute to the clinical emergence and exacerbation of vascular malformations in patients with initial subclinical presentation.

PERAN INTERLEUKIN-6 SELAMA INFEKSI VIRUS

This latter finding supports the hypothesis that upregulation of IL-6 during certain viral infections may increase viral survival and/or clinical disease exacerbation. The number of genes regulated by IL-6 activity may explain the pleotropic properties of these interleukins. The number of genes regulated by IL-6 activity may explain the pleotropic properties of these interleukins. Thus, the biological consequences of IL-6 production have been associated with pro and anti-inflammatory effects (Scheller et al., 2011), highlighting the important role of IL-6 in the activation and regulation of immune responses. Biological activities affected by IL-6 production include: controlling monocyte differentiation into macrophages by regulating the expression of macrophage colony-stimulating factors (Chomarat et al., 2000), increasing B cell IgG production by regulating IL-21 expression (Yang et al., 2016). ), negative regulation of dendritic cell maturation by activation of the STAT3 signaling pathway (Park et al., 2004), as well as promotion of Th2 responses by inhibiting Th1 polarization (Diehl and Rincon, 2002). Moreover, in combination with growth-altering beta factor, IL-6 induces the differentiation of naive CD4 into Th17 cells, which are essential for defense against pathogens at mucosal sites (Guglani and Khader, 2010). Also, the synergistic interaction of IL-6 with IL-7 and IL-15 induces the differentiation and cytolytic capacity of CD8 T cells (Cox et al., 2013). Importantly, IL-6 is a potent pyrogenic cytokine, and has an important role in regulating lymphocyte trafficking to lymphoid organs during febrile events (Evans et al., 2015).

Safety of mRNA COVID-19 vaccines in patients with well-controlled myasthenia gravis.

Introduction/AimsData on safety and tolerability of the vaccines against severe acute respiratory virus coronavirus‐2 (SARS‐CoV‐2, or coronavirus disease‐2019 [COVID‐19]) in patients with myasthenia gravis (MG) are currently limited. In this study we investigated the safety of mRNA‐based two‐dose vaccination in a cohort of patients with MG.MethodsThis investigation was a prospective observational study of messenger RNA (mRNA)‐based vaccines administered to patients with MG with stable disease. Local and systemic reactogenicity after injection was monitored for each dose administered. The patients were categorized and clinically assessed following the recommendations of the Myasthenia Gravis Foundation of America.ResultsThirty‐six males and 55 females (mean age at first vaccine dose, 58.8 years; standard deviation, = 17.1 years) received vaccines. Seventy‐two patients (79.1%) were taking one or more immunosuppressant(s). The most frequent adverse effects were injection‐site pain, fatigue, myalgia, chills, fever, and headache. Local and systemic reactions were transient; 58.2% of the patients developed one or more reaction(s). There were no anaphylactic reactions. None of the patients had a myasthenic crisis, and two developed a mild deterioration compared with their Quantitative Myasthenia Gravis baseline score. The clinical outcome scores showed no exacerbation of MG symptoms. Patients over 65 years of age developed fewer adverse effects. COVID‐19 vaccination did not induce clinical exacerbation in stable patients with MG, regardless of their age, sex, history of myasthenic crisis, or whether they were taking immunosuppressants.DiscussionOur data are consistent with the mRNA COVID‐19 vaccine being well tolerated in patients with well‐controlled MG. The findings may contribute to decisions in vaccination campaigns in the future.

A 3-Year Single Center Experience With Left Atrial Pressure Remote Monitoring: The Long and Winding Road.

BackgroundDespite continuous advancement in the field, heart failure (HF) remains the leading cause of hospitalization among the elderly and the overall first cause of hospital readmission in developed countries. Implantable hemodynamic monitoring is being tested to anticipate the clinical exacerbation onset, potentially preventing an emergent acute decompensation. To date, only pulmonary artery pressure (PAP) sensor received the approval to be implanted in symptomatic heart failure patients with reduced ejection fraction. However, PAP's indirect estimation of left ventricular filling pressure can be inaccurate in some contexts.MethodsThe VECTOR-HF study (NCT03775161) is examining the safety, usability and performance of the V-LAP system, a latest-generation device capable of continuously monitoring left atrial pressure (LAP). In our center, five advanced HF patients have been enrolled. After confirmation of the transmitted data reliability, LAP trends and waveforms have guided therapy optimization. The aim of this work is to share clinical insights from our center preliminary experience with V-LAP application.ResultsOver a median follow-up time of 18 months, LAP–based therapy optimization managed to reduce intracardiac pressure over time and no hospital readmission occurred. This result was paralleled by an improvement in both functional capacity (6MWT distance 352.5 ± 86.2 meters at baseline to 441.2 ± 125.2 meters at last follow-up) and quality of life indicators (KCCQ overall score 63.82 ± 16.36 vs. 81.92 ± 9.63; clinical score 68.47 ± 19.48 vs. 83.70 ± 15.58).ConclusionPreliminary evidence from V-LAP application at our institution support a promising efficacy. However, further study is needed to confirm the technical reliability of the device and to exploit the clinical benefit of left-sided hemodynamic remote monitoring.

Clinical Characteristics and Mortality of Non-tuberculous Mycobacterial Infection in Immunocompromised vs. Immunocompetent Hosts.

Immunosuppression and host vulnerability play a key role in non-tuberculous mycobacteria (NTM) pathogenesis. The objective of this study was to compare the clinical characteristics and mortality of NTM infections in immunocompromised and immunocompetent patients. We used a retrospective dataset obtained from our large, tertiary, urban, teaching hospital which is the medical records of hospitalized patients with NTM infections between January 1, 2013 to December 31, 2020. The information including clinical manifestations, imaging, and NTM etiological data were obtained from the hospital's clinical data system. A total of 480 patients with NTM infections completed species identification. 118 hospitalized NTM patients who met ATS/IDSA NTM diagnostic criteria and had complete medical records were included in the study. The average age was 49.4 years, 57 (48.3%) were female, and 64 (54.2%) were immunosuppressed hosts. In our study, the most common species in order of frequency were: M. intracellulare, M. abscessus, M. avium, and M. kansasii among NTM patients. The most common comorbidity was history of previous tuberculosis (30.5%). Besides malignancy, the most common immunodeficiencies were adult-onset immunodeficiency induced by anti-interferon-gamma autoantibody, SLE, and vasculitis. The immunocompromised patients with NTM had more clinical symptoms, comorbidities and lower lymphocyte counts compared to immunocompetent patients. The mortality we observed in immunocompromised patients of NTM disease was significantly higher than that of immunocompetent patients (HR 3.537, 95% CI 1.526–8.362). Immunosuppressed NTM patients with lower B and CD4+ T lymphocyte counts may more frequently present with disseminated NTM infections, clinical exacerbations, and higher mortality than immunocompetent patients.

Occurrence of Fibropapillomatosis in Green Turtles (Chelonia mydas) in Relation to Environmental Changes in Coastal Ecosystems in Texas and Florida: A Retrospective Study.

Simple SummaryIn the last few decades, sea turtles have been threatened by a disease called Fibropapillomatosis. Infection causes the growth of several tumors which can prevent affected turtles from seeing, swimming, and feeding properly, often with lethal outcomes. Fibropapillomatosis was described for the first time in Florida in 1938 and has since then increased and spread worldwide. To this day, there is no strong nor clear evidence on what causes the exacerbation of this disease which is associated with a herpesvirus. There is a consensus, however, that human-driven changes in the sea turtle habitats (i.e., climate change, pollution, urbanization) might play a role in increasing the number and severity of clinical cases. This study intends to explore the role of various possible environmental drivers behind the increased occurrence of this disease. We found that sea temperature, salinity, human population density, and river discharge from the coastline could be important drivers of tumor prevalence. Results from this preliminary work have the potential to offer an important baseline for future research on environmental drivers of Fibropapillomatosis. Fibropapillomatosis is a neoplastic disease of marine turtles, with green turtles (Chelonia mydas) being the most affected species. Fibropapillomatosis causes debilitating tumor growths on soft tissues and internal organs, often with lethal consequences. Disease incidence has been increasing in the last few decades and the reason is still uncertain. The potential viral infectious agent of Fibropapillomatosis, chelonid herpesvirus 5, has been co-evolving with its sea turtle host for millions of years and no major mutation linked with increased disease occurrence has been detected. Hence, frequent outbreaks in recent decades are likely attributable to external drivers such as large-scale anthropogenic changes in the green turtle coastal marine ecosystem. This study found that variations in sea surface temperature, salinity, and nutrient effluent discharge from nearby rivers were correlated with an increased incidence of the disease, substantiating that these may be among the significant environmental drivers impacting Fibropapillomatosis prevalence. This study offers data and insight on the need to establish a baseline of environmental factors which may drive Fibropapillomatosis and its clinical exacerbation. We highlight the multifactorial nature of this disease and support the inclusion of interdisciplinary work in future Fibropapillomatosis research efforts.

Exacerbation of immune thrombocytopenia following initial and booster vaccination with Pfizer-BioNTech COVID-19 vaccine

As the immune thrombocytopenia exacerbation rate after booster COVID-19 vaccines is unknown, we explore the rates after first, second and booster Pfizer-BioNTech COVID-19 vaccines. A retrospective study of adult ITP patients, receiving 1–3 vaccines was performed. The primary outcome was clinical ITP exacerbation defined as platelet count decrease requiring initiation/escalation of ITP treatment and/or new medical attention due to bleeding, within 3 months. Secondary outcome was any clinically relevant platelet decrease during the 3 months post-vaccination. The study included 93 ITP patients receiving 1 (n = 2), 2 (n = 22) or 3 (n = 69) vaccines. ITP exacerbation occurred in 2/93 (2.2%) patients following initial vaccination and in 3/69 (4.3%) following booster dose. Clinically relevant platelet decreases after initial doses occurred in 8/72 (11.1%) patients and in 8/39 (20.5%) after the booster. Clinical ITP exacerbation after booster doses did not follow clinical exacerbation after initial doses. Half of patients with clinically relevant platelet decreases after booster dose also had clinically relevant decreases following initial vaccination. We concluded that clinical ITP exacerbation is infrequent following Pfizer-BioNTech COVID-19 vaccine. Clinical exacerbation after booster doses was not preceded by clinical exacerbation after initial doses. Clinically relevant platelet decreases after booster doses occur frequently in patients with clinically relevant decreases after initial doses.

Evaluation of antioxidant status and oxidative stress markers in HTLV-1 infected individuals: correlation with the severity of virus-induced complications.

Introduction. Human T-cell lymphotropic virus type 1 (HTLV-1), a well-known member of the retroviridae family, potentially causes serious outcomes including adult T-cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP). Oxidative stress plays a key role in progression and clinical exacerbation of several chronic infections. We have previously shown a reduction in serum total antioxidant capacity (TAC) during HTLV-1 infection and this study was set out to investigate the reasons for TAC reduction.Hypothesis/Gap Statement. Oxidant/antioxidant imbalance during HTLV-1 infection may result from disruptions in oxidant levels or antioxidant defence system.Aim. This study aimed to analyse the key enzymes and oxidant molecules playing important roles in virus-induced oxidative stress.Methodology. We measured serum activities of the major antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) as well as serum concentrations of the main oxidant markers: nitric oxide (NO) and malondialdehyde (MDA). Totally 40 HTLV-1 infected patients and 40 healthy controls were enrolled in this study. The patient group consisted of chronic carriers and patients with HAM-TSP (N=20).Results. The current study found that serum levels of MDA and NO were significantly higher in patient groups particularly in HAM-TSP patients (P<0.05). In addition, a reductive trend was observed in the serum activities of CAT, SOD, and GPX in HTLV-1 infected patients compared with healthy controls (P<0.05).Conclusion. Reduced activities of CAT, SOD, and GPX antioxidant enzymes along with the observed elevated concentrations of oxidant molecules may contribute to oxidative stress and worse outcomes during HTLV-1 infection.

RGMa Signal in Macrophages Induces Neutrophil-Related Astrocytopathy in NMO.

Repulsive guidance molecule-a (RGMa) is a glycosylphosphatidylinositol-linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin-4 (AQP4)-specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti-RGMa monoclonal antibody (RGMa-mAb). Using a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa-mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa-signaling in macrophages. In both NMO rats and an NMO-autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4-IgG-induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa-mAb treatment. RGMa-mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin-expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa-mAb treatment effectively ameliorated the severity of neuropathic pain. RGMa signaling in infiltrated macrophages is a critical driver of neutrophil-related astrocytopathy in NMO lesions, and RGMa-mAb may provide an efficient therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO. ANN NEUROL 2022;91:532-547.

The effect of Ma-Xin-Gan-Shi decoction on asthma exacerbated by respiratory syncytial virus through regulating TRPV1 channel

Ethnopharmacological relevanceThe incidence and mortality of bronchial asthma are increasing, and respiratory syncytial virus (RSV) is widely regarded as the common cause of clinical exacerbation of asthma. Ma-Xing-Gan-Shi decoction (MXGSD), a classic traditional Chinese medicine prescription, is well-known for treating respiratory diseases, while the mechanism of effecting on RSV-exacerbated asthma remains to be explored. Aim of the studyIn this study, we investigated the mechanism by which MXGSD exerts a protective effect on asthma exacerbated by RSV in vivo and in vitro. Materials and methodsMXGSD is composed of four Chinese medicine, including Ephedra intermedia Schrenk & C.A.Mey. (herbaceous stem, 27g), Prunus armeniaca L. (dry seed, 27g), Glycyrrhiza uralensis Fisch. (radix and rhizome, 18g), and Gypsum fibrosum (main component: CaSO4·2H2O, 54g). In the present study, the exacerbated asthmatic mice model with the treatment of OVA plus RSV was replicated, and accompanied by the TMT proteomic analysis and further experimental investigations. Then, the protective effect of MXGSD (13.2, 6.6, 3.3 g/kg/d, 7d) on the mice treated by OVA plus RSV, and the mechanism of regulating TRPV1 was explored. In addition, the intracellular Ca2+ concentration of 16HBE cells pretreated with MXGSD medicated serum was also tested after stimulation with the TRPV1 agonist capsaicin. ResultsThe results suggested that MXGSD could reduce the levels of inflammation cells, airway hyperresponsiveness, and pathological damage of lung tissue. TMT quantitative proteomics analysis and further experimental exploration revealed that MXGSD could reduce the levels of IL-4, IL-13, PGE2, and SP in BAL and down-regulate the expression of TRPV1 mRNA and protein in lung tissue. Furthermore, 16HBE cells stimulated by capsaicin showed an increased intracellular Ca2+ concentration, while the pretreatment of MXGSD medicated serum could reduce it. ConclusionMSGSD showed a protective effect on RSV-exacerbated asthma, which may be related to its regulation of TRPV1 expression and reduction of Th2 cytokines and neurogenic inflammatory mediators. It may provide an objective basis and reference for the clinical application of MXGSD.

Cost-Effectiveness of Umeclidinium/Vilanterol versus Salmeterol/Fluticasone in Elderly Patients with Chronic Obstructive Pulmonary Diseases in China.

BackgroundFixed dose dual bronchodilators such as long-acting muscarinic antagonists (LAMAs) plus long-acting β2-agonists (LABAs) are a new and important inhaled preparation for COPD treatment in China. Among these, umeclidinium/vilanterol (UMEC/VIL) is increasingly being used in China, especially among the elderly.PurposeThis study aimed to assess the cost-effectiveness of maintenance treatment with UMEC/VIL compared with salmeterol/fluticasone (FSC) as one of the main therapeutic drugs for moderate to very severe COPD in China.MethodsA Markov model was developed to estimate the costs and outcomes from a societal perspective in a 10-year time horizon. Patients with moderate-to-very severe COPD were treated with UMEC/VIL (62.5/25µg) or FSC (50/500ug). Data concerning clinical efficacy, costs, utilities, transition probability, exacerbation rate, and mortality were obtained from the published literature and official government datasets. The costs were presented in US dollars based on 2021 prices. The indicators of total costs, life years (LYs), quality-adjusted life-years (QALYs), and mortality were used as the model output. Costs and outcomes were discounted at a 5% annual rate. Incremental cost-effectiveness ratios were calculated considering the threshold recommended by WHO. One-way and probabilistic sensitivity analyses were conducted to assess the stability of results.ResultsCompared with FSC, treatment with UMEC/VIL could save $1947.18, with a gain of 0.12 life-years and 0.05 QALYs. Further, 28.0% patients treated with UMEC/VIL and 29.2% patients treated with FSC were predicted to die after 10 years. Incremental cost effectiveness analysis showed that UMEC/VIL was dominant to FSC. Sensitivity analyses confirmed that the results were robust.ConclusionUMEC/VIL is a cost-effective treatment option compared with FSC among patients with moderate-to-very severe COPD.

Experience with cladribine tablets for highly active multiple sclerosis in real clinical practice

Objective: to evaluate the efficacy and safety of cladribine tablets as a treatment for immune reconstitution of highly active multiple sclerosis (HAMS) in general clinical practice.Patients and methods. 34 patients with HAMS who were followed up at the Moscow Multiple Sclerosis Center in 2018–2021 received two full treatment courses. HAMS diagnosis was established in the presence of two or more exacerbations per year without treatment or one exacerbation in patients receiving pathogenetic treatment in the presence of concomitant manifestations of the activity of the pathological process on MRI. Before initiation of cladribine therapy, the median exacerbation rate was 2.3 per year, i.e., 34 patients per year had a total of 78 exacerbations.Results and discussion. Only two clinical exacerbations were registered (one each in the first and second year) during two years of treatment among all 34 patients, the average frequency of exacerbations was 0.05 per year; in three cases, a subclinical exacerbation was noted - new Gd+ lesions on T2-weighted images on MRI, the total number of events was 0.15 per year. No significant adverse events were reported.Conclusion. Cladribine tablets are a highly effective and safe treatment option for HAMS.

Respiratory Effects of Treatment with a Glucagon-Like Peptide-1 Receptor Agonist in Patients Suffering from Obesity and Chronic Obstructive Pulmonary Disease.

PurposeChronic obstructive pulmonary disease (COPD) affects millions of people worldwide. Obesity is commonly seen concomitantly with COPD. People with COPD have reduced quality of life, reduced physical activity, chronic respiratory symptoms, and may suffer from frequent clinical exacerbations. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for weight loss and treatment of type-2 diabetes mellitus. In addition, liraglutide exerts anti-inflammatory actions by reducing IL-6 and MCP-1 levels. We investigated the effect of liraglutide on pulmonary function in people suffering from obesity and COPD.Patients and MethodsIn this controlled, double-blind trial, 40 people with obesity and COPD from two outpatient clinics were allocated randomly to receive liraglutide (3.0 mg, s.c.) or placebo (s.c.) for 40 weeks. At baseline and after 4, 20, 40, and 44 weeks, participants underwent pulmonary-function tests, 6-min walking test, and replied to a questionnaire regarding the clinical impact of COPD (COPD assessment test (CAT)-score).ResultsCompared with placebo, liraglutide use resulted in significant weight loss, increased forced vital capacity (FVC) and carbon monoxide diffusion capacity, and improved CAT-score. We found no significant changes in forced expiratory volume in one second (FEV1), FEV1/FVC, or 6-min walking distance.ConclusionIn patients suffering from obesity and COPD, 40 weeks of treatment with liraglutide improved some measures of pulmonary function. Our study suggests that liraglutide at 3.0 mg may be appropriate treatment in patients with obesity and COPD.

Do Not Give Up Your Stethoscopes Yet-Telemedicine for Chronic Respiratory Diseases in the Era of COVID-19.

Telemedicine in its many forms has been utilized across numerous medical specialties to facilitate and expand access to medical care, optimize existing healthcare infrastructure to encourage patient–provider communication, reduce provider burnout, and improve patient surveillance. Since the emergence of the novel coronavirus (COVID-19) pandemic there has been widening of existing socioeconomic disparities in healthcare access for those with chronic respiratory diseases, sparking interest in expanding the use of telemedicine modalities to enhance access to pulmonology specialist care, pulmonary rehabilitation, symptom monitoring, and early identification of clinical exacerbations. Furthermore, the use of telemedicine has been expanded into the intensive care setting to improve patient outcomes and offset provider demands following the increase in critically ill patients due to COVID-19. While an invaluable modality by which to broaden healthcare access and increase the efficacy of care delivery, telemedicine must be used in conjunction with face-to-face physical evaluation and appropriate clinical testing to optimize its benefit. We present here our view of the benefits and disadvantages of the use of telemedicine in the management of chronic respiratory disorders from the perspective of practicing clinicians.