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The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.
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PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.
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Antitussígenos , Codeína , Humanos , Codeína/uso terapêutico , Antitussígenos/uso terapêutico , Estudos Prospectivos , Tosse Crônica , Estudos de Coortes , Tosse/tratamento farmacológico , Tosse/etiologiaRESUMO
BACKGROUND: Carboplatin administration poses a risk of immediate hypersensitivity reactions (IHRs) that tend to increase with repeated administration and are mostly IgE-mediated. OBJECTIVE: This study evaluated the usefulness of carboplatin-prescreening intradermal skin tests (IDTs). METHODS: Carboplatin-prescreening IDTs were routinely conducted in patients with a history of receiving six or more carboplatin cycles beginning in January 2021. The primary objective was to assess disparities in the incidence of unanticipated IHRs to carboplatin administration. We compared patients in the intervention group (from 2021 to 2022) and those who did not undergo prescreening IDTs under the same conditions (preintervention group, from 2019 to 2020). Secondary objectives included evaluating the sensitivity and specificity of the prescreening IDT and the incidence of carboplatin IHR according to the number of infusion cycles. RESULTS: The intervention group was composed of 67 patients who were administered 347 carboplatin cycles whereas the preintervention group included 96 patients who were administered 464 carboplatin cycles. The risk of unanticipated carboplatin IHRs decreased by 83.2% in the intervention group compared with results in the preintervention group (preintervention group, 3.45%, n = 16 vs intervention group, 0.58%, n = 2; P = .005). The prescreening IDT showed a sensitivity and specificity of 77.78% and 99.41%, respectively. The risk of newly developed IHRs based on the number of carboplatin cycles was less than 1% (cycles 1-5), 2.11% (cycle 6), 3.90% (cycles 7-12), 2.90% (cycles 13-18), and 0.74% (cycles 19 and greater), respectively. CONCLUSIONS: Initiating carboplatin-prescreening IDTs from the seventh cycle on significantly reduced the risk of unanticipated IHRs.
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Hipersensibilidade a Drogas , Hipersensibilidade Imediata , Humanos , Carboplatina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Testes Intradérmicos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/complicações , Sensibilidade e Especificidade , Testes Cutâneos/efeitos adversosRESUMO
Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.
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Background The recurrence of hypersensitivity reaction (HSR) to low-osmolar iodinated contrast media (LOCM) remains challenging despite premedication and substitution of the LOCM. Purpose To determine the optimal practical preventive strategy for LOCM substitution in patients with a history of prior immediate HSR to LOCM. Materials and Methods In a retrospective study, patients with an immediate HSR to LOCM before February 2020 and who underwent subsequent exposure to LOCM until March 2021 were enrolled in five tertiary referral hospitals in South Korea. The association of recurrence of an HSR after subsequent LOCM exposures was assessed using multivariate general estimating equation analysis according to age, sex, the severity of the index HSR, premedication, and substituting LOCM based on common carbamoyl side chains, including the N-(2,3-dihydroxypropyl)-carbamoyl and N-(2,3-dihydroxypropyl)-N-methyl-carbamoyl moieties. Results The evaluation included 3800 subsequent LOCM exposures in 1066 patients (mean age, 56.2 years ± 13.5 [SD]; 567 [53%] female and 499 [47%] male patients). The general estimating equation analysis, using 1:1 propensity score matched data for age, sex, HSR severity, and LOCM selection, showed that premedication with corticosteroids significantly reduced recurrent HSR (odds ratio [OR], 0.72; 95% CI: 0.52, 1.00; P = .049). The change to another LOCM with a common side chain had a similar recurrence rate as using the same LOCM (OR, 0.98; 95% CI: 0.64, 1.50; P = .93), whereas the use of a different LOCM without a common side chain significantly lowered HSR recurrence (OR, 0.51; 95% CI: 0.37, 0.69; P < .001) in multivariate general estimating equation analysis. Substitution of an LOCM without a common side chain was effective regardless of the index HSR severity but was more pronounced in moderate-to-severe reactions (OR, 0.30; 95% CI: 0.16, 0.55; P < .001). Conclusion For patients with a previous immediate HSR of any severity to LOCM, alternative LOCM without a common carbamoyl side chain reduced recurrent HSR during subsequent exposures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by McDonald in this issue.
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Hipersensibilidade Imediata , Hipersensibilidade , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Meios de Contraste/efeitos adversos , Estudos Retrospectivos , Análise MultivariadaRESUMO
PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.
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Refluxo Gastroesofágico , Hipersensibilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Crônica , Tosse/diagnóstico , Tosse/epidemiologia , Tosse/etiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Estudos Prospectivos , Qualidade de Vida , República da Coreia/epidemiologiaRESUMO
Background: While tools exist for objective cough counting in clinical studies, there is no available tool for objective cough measurement in clinical practice. An artificial intelligence (AI)-based cough count system was recently developed that quantifies cough sounds collected through a smartphone application. In this prospective study, this AI-based cough algorithm was applied among real-world patients with an acute exacerbation of asthma. Methods: Patients with an acute asthma exacerbation recorded their cough sounds for 7 days (2 consecutive hours during awake time and 5 consecutive hours during sleep) using CoughyTM smartphone application. During the study period, subjects received systemic corticosteroids and bronchodilator to control asthma. Coughs collected by application were counted by both the AI algorithm and two human experts. Subjects also provided self-measured peak expiratory flow rate (PEFR) and completed other outcome assessments [e.g., cough symptom visual analogue scale (CS-VAS), awake frequency, salbutamol use] to investigate the correlation between cough and other parameters. Results: A total of 1,417.6 h of cough recordings were obtained from 24 asthmatics (median age =39 years). Cough counts by AI were strongly correlated with manual cough counts during sleep time (rho =0.908, P<0.001) and awake time (rho =0.847, P<0.001). Sleep time cough counts were moderately to strongly correlated with CS-VAS (rho =0.339, P<0.001), the frequency of waking up (rho =0.462, P<0.001), and salbutamol use at night (rho =0.243, P<0.001). Weak-to-moderate correlations were found between awake time cough counts and CS-VAS (rho =0.313, P<0.001), the degree of activity limitation (rho =0.169, P=0.005), and salbutamol use at awake time (rho =0.276, P<0.001). Neither awake time nor sleep time cough counts were significantly correlated with PEFR. Conclusions: The strong correlation between cough counts using the AI-based algorithm and human experts, and other indicators of patient health status provides evidence of the validity of this AI algorithm for use in asthma patients experiencing an acute exacerbation. Study findings suggest that CoughyTM could be a novel solution for objectively monitoring cough in a clinical setting.
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BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.
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Hipersensibilidade a Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersensibilidade Imediata , Hipersensibilidade , Compostos de Iodo , Humanos , Meios de Contraste/efeitos adversos , Estudos Prospectivos , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade Imediata/induzido quimicamente , Testes Cutâneos/efeitos adversos , Compostos de Iodo/efeitos adversos , Hipersensibilidade/complicaçõesRESUMO
PURPOSE: Chronic cough (CC) is associated with health-related quality of life (HRQoL) impairment. However, the determinants of HRQoL are under-investigated. METHODS: Patients aged 19-80 years with CC were prospectively recruited from 10 referral clinics. Comparisons were made with age- and sex-matched controls (1:4 ratio) selected from a Korean general population survey database; 1) a group without current cough (non-cough controls) and 2) another group without major chronic illnesses (healthy controls). HRQoL was assessed using the EuroQoL 5-dimension (EQ-5D) index. In CC patients, cough-specific patient-reported outcomes (PROs) were additionally measured. Cross-sectional analyses were performed to evaluate demographic and clinical parameters associated with the EQ-5D index of CC patients. RESULTS: A total of 200 CC patients (137 newly referred with CC and 63 refractory or unexplained CC [RUCC] patients), 800 non-cough controls, and 799 healthy controls were analyzed. The EQ-5D index of CC patients was significantly lower than that of non-cough controls or healthy controls (0.82 ± 0.14 vs 0.92 ± 0.14/0.96 ± 0.08; P < 0.001, respectively). The index was also associated with older age (≥ 60 years), female sex, and comorbidities such as asthma or depression. Among the patients with CC, the index was significantly lower in patients with RUCC than in those with newly referred CC, being treated with codeine or cough neuromodulators, or with cough-related fatigue. In Spearman analyses, the EQ-5D index correlated with cough-specific quality of life and cough severity scores, not with throat sensation or cough trigger scores. CONCLUSIONS: The HRQoL impairment of CC patients was associated with older age, female sex, and comorbidities but it was also affected by cough severity, complications, treatments, and treatment responses. Longitudinal studies are warranted to further understand and improve the HRQoL of CC patients.
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BACKGROUND: Accumulating evidence suggests that the gut microbiome is associated with asthma. However, altered gut microbiome in adult asthma is not yet well established. We aimed to investigate the gut microbiome profiles of adult asthmatic patients with symptomatic eosinophilic inflammation. METHODS: The 16 s rRNA gene metagenomic analysis of feces in the symptomatic eosinophilic asthma group (EA, n = 28) was compared with the healthy control (HC, n = 18) and the chronic cough control (CC, n = 13). A correlation analysis between individual taxa and clinical markers was performed within the EA group. Changes in the gut microbiome were examined in patients with significant symptom improvement in the EA group. RESULTS: The relative abundances of Lachnospiraceae and Oscillospiraceae significantly decreased and Bacteroidetes increased in the EA group. Within EA group, Lachnospiraceae was negatively correlated with indicators of type 2 inflammation and lung function decline. Enterobacteriaceae and Prevotella was positively associated with type 2 inflammation and lung function decline, respectively. The abundance of predicted genes associated with amino acid metabolism and secondary bile acid biosynthesis was diminished in the EA group. These functional gene family alterations could be related to gut permeability, and the serum lipopolysaccharide concentration was actually high in the EA group. EA patients with symptom improvement after 1 month did not show a significant change in the gut microbiome. CONCLUSIONS: Symptomatic eosinophilic adult asthma patients showed altered the gut microbiome composition. Specifically, a decrease in commensal clostridia was observed, and a decrease in Lachnospiraceae was correlated with blood eosinophilia and lung function decline.
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Asma , Microbioma Gastrointestinal , Eosinofilia Pulmonar , Humanos , Adulto , Asma/genética , Inflamação/genética , Metagenoma , RNA Ribossômico 16S/genéticaRESUMO
Growing evidence suggests that there is an essential link between the gut and lungs. Asthma is a common chronic inflammatory disease and is considered a heterogeneous disease. While it has been documented that eosinophilic asthma affects gut immunity and the microbiome, the effect of other types of asthma on the gut environment has not been examined. In this study, we utilized an OVA/poly I:C-induced mixed granulocytic asthma model and found increased Tregs without significant changes in other inflammatory cells in the colon. Interestingly, an altered gut microbiome has been observed in a mixed granulocytic asthma model. We observed an increase in the relative abundance of the Faecalibaculum genus and Erysipelotrichaceae family, with a concomitant decrease in the relative abundance of the genera Candidatus arthromitus and Streptococcus. The altered gut microbiome leads to changes in the abundance of genes associated with microbial metabolism, such as glycolysis. We found that mixed granulocytic asthma mainly affects the gut microbial composition and metabolism, which may have important implications in the severity and development of asthma and gut immune homeostasis. This suggests that altered gut microbial metabolism may be a potential therapeutic target for patients with mixed granulocytic asthma.
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Background and Aim: Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling. Methods: Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud. Results: The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group. Conclusion: Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.
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Clostridioides difficile , Infecções por Clostridium , Microbioma Gastrointestinal , Deficiência de Vitamina D , Bactérias/genética , Colecalciferol , Infecções por Clostridium/microbiologia , Suplementos Nutricionais , Humanos , Estudos Prospectivos , RNA Ribossômico 16S/genética , Vancomicina , Vitamina D , Deficiência de Vitamina D/microbiologiaRESUMO
BACKGROUND: Probiotics have been shown to prevent various allergic diseases by producing extracellular vesicles (EVs). However, the role of EVs in allergic asthma has not yet been completely determined. METHODS: Gut microbial composition, mainly genera related to probiotics, was investigated in allergic asthmatic mice. Moreover, EVs were isolated from Lactococcus lactis (L. lactis, a selected bacterium) and EV proteins were identified by peptide mass fingerprinting. EV functions in immune responses were evaluated in vivo or ex vivo. Furthermore, the levels of specific IgG antibodies (an alternative marker for EV quantification) to L. lactis-EVs were measured by ELISA in the sera of 27 asthmatic patients and 26 healthy controls. RESULTS: Allergic asthmatic mice showed a lower proportion of Lactococcus compared to healthy mice. L. lactis was cultured and its EVs abundantly contained pyruvate kinase. When allergic asthmatic mice were intranasally treated with EVs, airway hyperresponsiveness, eosinophil number, cytokine secretion, and mucus production were significantly decreased. Moreover, L. lactis-EV treatment shifted immune responses from Th2 to Th1 by stimulating dendritic cells to produce IL-12. In addition, significantly lower levels of serum specific IgG4 (but not IgG1) to L. lactis-EVs were noted in asthmatic patients than in healthy controls. A positive correlation between the levels of EV-specific IgG4 and FEV1 (%), but a negative correlation between the levels of EV-specific IgG4 and IL-13 were observed. CONCLUSION: These findings suggest that L. lactis-EVs may have immune-regulating effects on airway inflammation mediated by dendritic cell activation, providing a potential benefit for allergic asthma.
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BACKGROUND: Staphylococcus aureus (SA) nasal carriage (SA carriage) and IgE-sensitization to SA enterotoxin (SE IgE-sensitization) are known to be associated with chronic airway disease. OBJECTIVE: This study aimed to evaluate the differences in risk factors, type 2 inflammation and respiratory symptoms between SA carriage and SE IgE-sensitization. METHODS: We conducted a cross-sectional study of a community-based adult population to evaluate the environmental exposure and health impact of the Pohang Industrial Complex, Korea. Participants were examined based on self-reported questionnaires, nasal swab, and blood sampling. RESULTS: There were 307 participants, and the overall prevalence of SA carriage and SE IgE-sensitization was 26.1% (80/307) and 25.7% (79/307), respectively. An urban environment was significantly correlated with SA carriage, whereas age and obesity were significantly correlated with SE IgE-sensitization. SA carriage was not associated with an increase in total IgE and blood eosinophil count, whereas SE IgE-sensitization was associated with an increased total IgE and blood eosinophil count. SA carriage was significantly correlated with cough persisting for more than three weeks (OR, 3.044; 95% CI, 1.137-8.153) and sputum (OR, 2.429; 95% CI, 1.008-5.854). SE IgE-sensitization was a significant correlation with only sputum (OR, 2.452; 95% CI, 1.066-5.640). SA carriage and SE IgE-sensitization showed a synergistic effect on the prevalence of cough and sputum. CONCLUSION: SA carriage was associated with the urban environment, and SE IgE-sensitization was associated with the elderly and obesity. SA carriage and SE IgE-sensitization had different correlation with type 2 inflammation and airway symptoms.
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INTRODUCTION: Although factors initiating the inflammatory response to monosodium urate crystals have been identified, the role of the gut microbiota and their metabolites on gout remains unknown. This study aimed to investigate the changes in both gut microbiota and short-chain fatty acids (SCFAs) according to inflammatory states of gout in the same patients. METHODS: This study enrolled 20 patients with gout in the acute state who had active joints and were followed up until the recovery state with no active joints. Blood and fecal samples were simultaneously collected within 3 days for each disease state. The stool microbiome was analyzed using 16S rRNA sequencing, and serum SCFAs were measured by gas chromatography-mass spectrometry. Differences in the gut microbiome and serum SCFAs were compared between the acute and recovery states. RESULTS: Beta diversity of the microbiome was significantly different between the acute and recovery states in terms of weighted UniFrac distance. In the recovery state, Prevotellaceae (p = 0.006) and the genus Prevotella (p = 0.009) were significantly enriched, whereas Enterobacteriaceae (p = 0.019) and its derivative genus Shigella (p = 0.023) were significantly decreased compared to the acute state. Similarly, the levels of acetate were dramatically increased in the recovery state compared to the acute state (p < 0.010). The levels of propionate and butyrate tended to increase but without statistical significance. CONCLUSION: Substantial alterations of bacterial composition with the promotion of SCFA formation (especially acetate) were found after treatment in patients with gouty arthritis.
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Artrite Gotosa , Microbioma Gastrointestinal , Artrite Gotosa/tratamento farmacológico , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: The associations between long-term changes in body mass composition and decline in lung function in healthy adults are unknown. METHODS: Using a well-defined health check-up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m)2 ] or FM index (FMI) [FM (kg)/height (m)2 ] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups. RESULTS: A total of 15 476 middle-aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5-9) over an average follow-up period of 8.95 years (IQR: 6.73-11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m2 in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m2 in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10-10 and P < 2.0 × 10-16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss). CONCLUSIONS: Change in body composition over time can be used to identify healthy middle-aged individuals at high risk for rapid FEV1 decline.
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Composição Corporal , Músculo Esquelético , Adulto , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Pulmão , Masculino , Pessoa de Meia-IdadeRESUMO
Exacerbation is a defining feature of severe asthma, and oral corticosteroids (OCSs) are frequently prescribed to manage exacerbations. This qualitative study was conducted to examine the experience of patients with severe asthma, with a focus on asthma exacerbation and OCS treatment. Adults with severe asthma were recruited from three tertiary hospitals in South Korea. Data were collected through in-depth qualitative interviews. Verbatim transcripts were analysed using Colaizzi's phenomenological method to uncover the meaning of the participants' experience. Recruitment of participants continued until thematic saturation. 14 patients with severe asthma were recruited. Four theme clusters emerged: 1) experience of asthma exacerbation; 2) impact on life; 3) OCS treatments; and 4) disease perception. The patients experienced severe physical and psychosocial distress from asthma exacerbations, felt helpless due to failed efforts to prevent exacerbation and were living a restricted life due to fear of exacerbation. They feared OCS side-effects but had no other choice than to rely on OCSs because other interventions were ineffective. Most had poor knowledge and understanding of severe asthma and the long-term health consequences. Asthma exacerbation affects wide aspects of life in patients with severe asthma. Several components may underlie reliance on OCSs, including experience of distress during exacerbation, fear of future exacerbation and lack of proper knowledge about the long-term health consequences of severe asthma and OCS treatments. A multi-disciplinary approach is warranted to support the patients and to provide systematic education about the long-term health implications of severe asthma.
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ST-segment elevation myocardial infarction (STEMI) is characterized by thrombotic coronary artery occlusions caused by atherosclerotic plaque rupture. The gut microbiome potentially contributes to the pathogenesis of coronary artery diseases. This study investigated the microbial diversity and composition of coronary thrombi in STEMI patients and the composition of the thrombus microbiome relative to that of the oral and gut microbiomes. A case-control study was performed with 22 STEMI patients and 20 age- and sex-matched healthy controls. Coronary thrombi were acquired from STEMI patients via manual thrombus aspiration during primary coronary intervention. Oral swab and stool samples were collected from both groups, and 16S rRNA sequencing and metagenomic microbiome analyses were performed. Microbial DNA was detected in 4 of 22 coronary thrombi. Proteobacteria (p) and Bacteroidetes (p) were the most abundant phyla. The oral and gut microbiomes significantly differed between patients and healthy controls. The patient group presented microbial dysbiosis, as follows: a higher relative abundance of Proteobacteria (p) and Enterobacteriaceae (f) in the gut microbiome and a lower abundance of Firmicutes (p) and Haemophilus (g) in the oral microbiome. Furthermore, 4 significantly abundant genera were observed in the coronary thrombus in the patients: Escherichia, 1.25%; Parabacteroides, 0.25%; Christensenella, 0.0%; and Bacteroides, 7.48%. The present results indicate that the relative abundance of the gut and oral microbiomes was correlated with that of the thrombus microbiome.