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INTRODUCTION: After puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors. AIM: To evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting. METHODS: Demographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice. RESULTS: 3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58). CONCLUSIONS: Females had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.
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Asma , Humanos , Feminino , Masculino , Estudos Retrospectivos , Estudos Transversais , Asma/tratamento farmacológico , Asma/epidemiologia , Biomarcadores , Obesidade , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood. METHODS: Clinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real-world UK multi-centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed. RESULTS: In total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82-0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89-0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87-0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89-0.99, p < 0.05). CONCLUSIONS: In this long-term, real-world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission.
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Rationale: Pneumococcal pneumonia remains a global health problem. Pneumococcal colonization increases local and systemic protective immunity, suggesting that nasal administration of live attenuated Streptococcus pneumoniae (Spn) strains could help prevent infections. Objectives: We used a controlled human infection model to investigate whether nasopharyngeal colonization with attenuated S. pneumoniae strains protected against recolonization with wild-type (WT) Spn (SpnWT). Methods: Healthy adults aged 18-50 years were randomized (1:1:1:1) for nasal administration twice (at a 2-wk interval) with saline solution, WT Spn6B (BHN418), or one of two genetically modified Spn6B strains, SpnA1 (Δfhs/piaA) or SpnA3 (ΔproABC/piaA) (Stage I). After 6 months, participants were challenged with SpnWT to assess protection against the homologous serotype (Stage II). Measurements and Main Results: 125 participants completed both study stages per intention to treat. No serious adverse events were reported. In Stage I, colonization rates were similar among groups: SpnWT, 58.1% (18 of 31); SpnA1, 60% (18 of 30); and SpnA3, 59.4% (19 of 32). Anti-Spn nasal IgG levels after colonization were similar in all groups, whereas serum IgG responses were higher in the SpnWT and SpnA1 groups than in the SpnA3 group. In colonized individuals, increases in IgG responses were identified against 197 Spn protein antigens and serotype 6 capsular polysaccharide using a pangenome array. Participants given SpnWT or SpnA1 in Stage I were partially protected against homologous challenge with SpnWT (29% and 30% recolonization rates, respectively) at stage II, whereas those exposed to SpnA3 achieved a recolonization rate similar to that in the control group (50% vs. 47%, respectively). Conclusions: Nasal colonization with genetically modified live attenuated Spn was safe and induced protection against recolonization, suggesting that nasal administration of live attenuated Spn could be an effective strategy for preventing pneumococcal infections. Clinical trial registered with the ISRCTN registry (ISRCTN22467293).
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Infecções Pneumocócicas , Streptococcus pneumoniae , Adulto , Humanos , Virulência , Nariz , Infecções Pneumocócicas/prevenção & controle , Imunização , Anticorpos Antibacterianos , Imunoglobulina G , Vacinas Pneumocócicas/uso terapêuticoRESUMO
BACKGROUND: Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. METHODS: This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1â s above lower limit of normal or no more than 100â mL less than baseline. RESULTS: 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. CONCLUSIONS: 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.
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Antiasmáticos , Asma , Produtos Biológicos , Humanos , Feminino , Masculino , Estudos Retrospectivos , Asma/tratamento farmacológico , Biomarcadores , Sistema de Registros , Terapia Biológica , Produtos Biológicos/uso terapêutico , Reino Unido , Antiasmáticos/uso terapêuticoRESUMO
Rationale: Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 µl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Measurement and Main Results: Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Criança , Lactente , Adulto Jovem , Adulto , Sorogrupo , Portador Sadio , Vacinas Pneumocócicas/uso terapêutico , Infecções Pneumocócicas/prevenção & controle , Nasofaringe/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologiaRESUMO
BACKGROUND: several biological treatments have become available for management of severe asthma. There is a significant overlap in the indication of these treatments with lack of consensus on the first-line biologic choice and switching practice in event of treatment failure. AIMS: to evaluate outcomes of biologic treatments through analysis of the UK Severe Asthma Registry (UKSAR), and survey of the UK severe asthma specialists' opinion. METHODS: patients registered in the UKSAR database and treated with biologics for severe asthma in the period between January 2014 and August 2021, were studied to explore biologic treatments practice. This was complemented by survey of opinion of severe asthma specialists. RESULTS: a total of 2,490 patients from 10 severe asthma centres were included in the study (mean age 51.3 years, 61.1% female, mean BMI 30.9kg/m2 ). Biologics use included mepolizumab 1,115 (44.8%), benralizumab 925 (37.1%), omalizumab 432 (17.3%), dupilumab 13 (0.5%), and reslizumab 5 (0.2%). Patients on omalizumab were younger and had earlier age of onset asthma than those prescribed mepolizumab or benralizumab. Patients prescribed mepolizumab and benralizumab had similar clinical characteristics. Those on benralizumab were more likely to continue treatment at approximately one year follow up (93.9%), than those on mepolizumab (80%), or omalizumab (69.6%). The first choice biologic differed between centres and changed over the study time period. Experts' opinion also diverged in terms of biologic initiation choice and switching practice. CONCLUSION: We observed significant variation and divergence in the prescribing practices of biologics in severe asthma that necessitates further research and standardisation.
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Antiasmáticos , Asma , Indução de Remissão , Humanos , Asma/tratamento farmacológico , Antiasmáticos/uso terapêutico , Índice de Gravidade de Doença , Masculino , Feminino , Terapia Biológica/métodos , Pessoa de Meia-Idade , Produtos Biológicos/uso terapêutico , Adulto , Resultado do TratamentoRESUMO
PURPOSE: Patients with obstructive pulmonary disease (asthma or chronic obstructive pulmonary disease-COPD) who smoke illicit drugs are at an increased risk of hospital admissions. We compared hospital readmission rates due to exacerbations of obstructive pulmonary disease amongst patients who were current/ex-illicit drug smokers versus current/ex-tobacco smokers. METHODS: We reviewed all the admissions between January 2009 and September 2011 with a presumptive diagnosis of an 'exacerbation of COPD' retrospectively from our COPD admission database. RESULTS: There were 950 sequential hospital admissions in 709 patients over a 33-month period; 250 ex-tobacco smokers, 370 current tobacco smokers and 89 current/ex-illicit drug smokers. Recurrent hospital admission rates with exacerbation of obstructive pulmonary disease were higher in the illicit drug smokers compared with current/ex-tobacco smokers (1.00 versus 0.22/0.26, p < 0.001). Illicit drug smokers were younger [50 versus 72.9/69.9 (mean 71.2) years, p < 0.001] and had shorter length of hospital stay [7.44 versus 9.28/10.69 (mean 9.87) days, p = 0.038]. Illicit drug smokers with FEV1 < 1 litre (L) had higher readmissions than ex/current tobacco smokers with FEV1 < 1 L (p < 0.001). Admissions requiring non-invasive ventilation for type 2 respiratory failure were more common in illicit drug smokers (8.4 versus 3 %, p < 0.002). CONCLUSION: We have shown that readmission rates in illicit drug smokers with FEV1 < 1 L are higher than in tobacco smokers. Studies are needed to determine whether targeting these illicit drug users with an intensive community intervention package (to include early therapy, pulmonary rehabilitation) will reduce readmission rates in this often neglected population.
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Pulmão/fisiopatologia , Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumar/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Idoso , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Bases de Dados Factuais , Progressão da Doença , Inglaterra , Feminino , Volume Expiratório Forçado , Dependência de Heroína/complicações , Dependência de Heroína/fisiopatologia , Humanos , Tempo de Internação , Masculino , Abuso de Maconha/complicações , Abuso de Maconha/fisiopatologia , Fumar Maconha/efeitos adversos , Fumar Maconha/fisiopatologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Abandono do Hábito de Fumar , Prevenção do Hábito de Fumar , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Type 2 (T2) low severe asthma phenotype is often a result of corticosteroid-overtreated T2-disease due to persistent symptoms, often not related to asthma, and unlikely to respond to high-dose corticosteroid treatment. OBJECTIVE: This study aimed to characterise severe asthma patients with low eosinophil counts (<300 cells/µl) and describe their disease burden and treatment across healthcare settings in the UK. METHODS: A retrospective cohort study of severe asthma patients using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients on latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and healthcare resource use (HCRU) were described by baseline BEC (≤150 and >150 to <300 cells/µl). RESULTS: Analysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; with 60.5% and 59.4% having BECs ≤150 cells/µl at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (≥2 exacerbations) at follow-up (12-months post-index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance OCS use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 µg SABA or >500 µg terbutaline/day in CPRD-HES: 48.8%; median ACQ-6 score in UKSAR: 2.0 [1.0-3.3]). HCRU were similar across BEC groups. CONCLUSION: Most patients managed in primary care were infrequent exacerbators, whilst UKSAR patients exacerbated frequently. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance OCS, increasing risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.
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Mãos/microbiologia , Infecções Pneumocócicas/transmissão , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/microbiologia , Streptococcus pneumoniae/genética , Adulto JovemRESUMO
BACKGROUND: Biologic therapies such as mepolizumab and benralizumab offer treatment options for severe eosinophilic asthma (SEA), although long-term real-world data on their use are limited. OBJECTIVES: To evaluate the impact of benralizumab and mepolizumab treatment among biologic-naive patients with SEA over 36 months and describe the incidence of super-response at 12 and 36 months, identifying potential predictive factors. METHODS: We conducted a retrospective, single-center study of patients with SEA who were given mepolizumab or benralizumab from May 2017 to December 2019, and who completed 36 months of therapy. Baseline demographics, comorbidities, and medication use were described. Data on clinical outcomes, including maintenance oral corticosteroid (OCS) use, annual exacerbation rate (AER), mini Asthma Quality of Life Questionnaire, Asthma Control Questionnaire (ACQ-6), and eosinophil count were collected at baseline and at 12 and 36 months. Super-response was evaluated at 12 and 36 months. RESULTS: A total of 81 patients were included. Maintenance OCS use significantly improved from baseline (5.3 mg/d) to 12 months (2.4 mg/d, P < .0001) and 36 months (0.6 mg/d; P < .0001). Annual exacerbation rate decreased from baseline (5.8) to 12 months (0.9; P < .0001) and 36 months (1.2; P < .0001). Mini Asthma Quality of Life Questionnaire, ACQ-6, and eosinophil count significantly improved from baseline to 12 and 36 months. Twenty-nine patients demonstrated super-response at 12 months. Compared with those without a super-response, these patients had better baseline AER (4.7 vs 6.5; P = .009), mini Asthma Quality of Life Questionnaire (3.41 vs 2.54; P = .002), and ACQ-6 (3.38 vs 4.06; P = .03) scores. Most maintained a super-response up to 36 months. CONCLUSIONS: Mepolizumab and benralizumab are associated with significant improvements in OCS use, AER, and asthma control in real-world cohorts for up to 36 months, providing insight into long-term use for SEA.
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Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Antiasmáticos/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Asma/tratamento farmacológico , Asma/etiologia , Eosinofilia Pulmonar/tratamento farmacológico , Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
Dynamic chest radiography (DCR) is a real-time sequential high-resolution digital X-ray imaging system of the thorax in motion over the respiratory cycle, utilising pulsed image exposure and a larger field of view than fluoroscopy coupled with a low radiation dose, where post-acquisition image processing by computer algorithm automatically characterises the motion of thoracic structures. We conducted a systematic review of the literature and found 29 relevant publications describing its use in humans including the assessment of diaphragm and chest wall motion, measurement of pulmonary ventilation and perfusion, and the assessment of airway narrowing. Work is ongoing in several other areas including assessment of diaphragmatic paralysis. We assess the findings, methodology and limitations of DCR, and we discuss the current and future roles of this promising medical imaging technology.Critical relevance statement Dynamic chest radiography provides a wealth of clinical information, but further research is required to identify its clinical niche.
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BACKGROUND: The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown. METHODS: Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed. RESULTS: A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p<0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p<0.01)and increased with age (p<0.01). Reliability of the instrument was high (over 88%) in all subgroups studied. CONCLUSION: The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.
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Asma , Masculino , Feminino , Humanos , Idoso , Reprodutibilidade dos Testes , Teorema de Bayes , Psicometria , Inquéritos e Questionários , Asma/diagnósticoRESUMO
INTRODUCTION: Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies. METHODS: A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation. RESULTS: In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety. DISCUSSION: No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated. CONCLUSION: Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Adulto , Humanos , Adulto Jovem , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Nasofaringe , Antibacterianos/efeitos adversosRESUMO
BACKGROUND: Benralizumab is an IL-5 receptor alpha-directed cytolytic mAb that depletes eosinophils, reducing exacerbations and oral corticosteroid (OCS) use, and improves asthma control for patients with severe eosinophilic asthma (SEA). Data on response in patients previously treated with other biologic therapies are limited. OBJECTIVE: To describe real-world clinical outcomes with benralizumab for patients with and without prior biologic use for uncontrolled SEA. METHODS: This retrospective study compared clinical outcomes before and after benralizumab initiation in adults with uncontrolled SEA with 3 or more asthma exacerbations in the previous 12 months or on maintenance OCS treatment. Outcomes included exacerbations, OCS use, patient-reported outcomes, and health care resource utilization, including emergency department visits and hospitalizations. RESULTS: In all, 208 patients were enrolled, including 90 (43.3%) with previous experience with an alternate biologic for SEA. Benralizumab led to an 81% reduction in exacerbation rate, with 48% of patients with previous exacerbations experiencing none after 48 weeks. Overall, 67% of patients requiring baseline maintenance OCS achieved greater than or equal to 50% reduction in daily OCS dosage, and 53% eliminated maintenance OCS. Clinically meaningful improvements in patient-reported outcomes were seen, with response at 4 weeks predicting longer-term benefits. Health care resource utilization also decreased. Improvements were observed irrespective of previous biologic experience, fractional exhaled nitric oxide concentrations, atopic status, or other baseline characteristics. CONCLUSIONS: In a multicenter real-world setting, patients with uncontrolled SEA achieved substantial improvements in all clinical outcome measures with benralizumab irrespective of previous biologic use, atopic status, or baseline fractional exhaled nitric oxide concentration.
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Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados , Asma/induzido quimicamente , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Eosinófilos , Humanos , Eosinofilia Pulmonar/tratamento farmacológico , Estudos RetrospectivosRESUMO
An increased incidence of pulmonary barotrauma in patients receiving CPAP for #COVID19 pneumonia was observed during the second peak of infections at this centre in the UK https://bit.ly/3qeSTp9.
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BACKGROUND: NHS England recommends non-invasive continuous positive airway pressure (CPAP) as a possible treatment for type 1 respiratory failure associated with COVID-19 pneumonitis, either to avoid intubation or as a ceiling of care. However, data assessing this strategy are sparse, especially for the use of CPAP as a ceiling of care, and particularly when delivered outside of a traditional critical care environment. We describe a cohort of patients from Liverpool, UK, who received CPAP on a dedicated respiratory surge unit at the start of the second wave of the COVID-19 pandemic in UK. METHODS: Retrospective cohort analysis of consecutive patients receiving CPAP for the treatment of respiratory failure secondary to COVID-19 on the respiratory surge unit at the Royal Liverpool Hospital, Liverpool, UK from 21 September until 30 November 2020. RESULTS: 88 patients were included in the analysis. 56/88 (64%) were deemed suitable for escalation to invasive mechanical ventilation (IMV) and received CPAP as a trial; 32/88 (36%) received CPAP as a ceiling of care. Median age was 63 years (IQR: 56-74) and 58/88 (66%) were men. Median SpO2/FiO2 immediately prior to CPAP initiation was 95 (92-152). Among patients for escalation to IMV, the median time on CPAP was 6 days (IQR 4-7) and survival at day 30 was 84% (47/56) with 14/56 (25%) escalated to IMV. Of those patients for whom CPAP was ceiling of care, the median duration of CPAP was 9 days (IQR 7-11) and 18/32 (56%) survived to day 30. Pulmonary barotrauma occurred in 9% of the cohort. There were no associations found on multivariant analysis that were associated with all-cause 30-day mortality. CONCLUSIONS: With adequate planning and resource redistribution, CPAP may be delivered effectively outside of a traditional critical care setting for the treatment of respiratory failure due to COVID-19. Clinicians delivering CPAP to patients with COVID-19 pneumonitis should be alert to the dangers of pulmonary barotrauma. Among patients who are for escalation of care, the use of CPAP may avoid the need for IMV in some patients. Our data support the NHS England recommendation to consider CPAP as a ceiling of care.