RESUMO
Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.
Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Rinite Alérgica , Rinite , Sinusite , Adulto , Humanos , Rinite/complicações , Rinite/tratamento farmacológico , Rinite/epidemiologia , Estudos de Coortes , Asma/complicações , Asma/tratamento farmacológico , Asma/epidemiologia , Comorbidade , Doença Crônica , Sinusite/tratamento farmacológico , Sinusite/epidemiologia , Produtos Biológicos/uso terapêutico , Rinite Alérgica/complicações , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/epidemiologia , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/epidemiologiaRESUMO
RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
RESUMO
BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female). RESULTS: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes. CLINICAL TRIAL REGISTRATION: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121).
Assuntos
Asma , Sinusite , Adulto , Humanos , Masculino , Feminino , Multimorbidade , Estudos Transversais , Asma/epidemiologia , Comorbidade , Sinusite/epidemiologia , Doença Crônica , Sistema de RegistrosRESUMO
BACKGROUND: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm. METHODS: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety. FINDINGS: Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals. INTERPRETATION: DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04382053.
Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Humanos , SARS-CoV-2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Síndrome do Desconforto Respiratório/tratamento farmacológicoRESUMO
Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.
Assuntos
Tratamento Farmacológico da COVID-19 , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Cuidados para Prolongar a Vida , Idoso , COVID-19/complicações , COVID-19/mortalidade , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Respiração Artificial , Choque Séptico/etiologia , Método Simples-CegoRESUMO
Asthma has been linked with prolonged time to pregnancy. Our aim was to explore a possible association between asthma and need for fertility treatment among women with live births.All women enrolled in the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital, Denmark were each matched with the next three consecutive women giving birth at Hvidovre Hospital. Information from the Danish National Assisted Reproductive Technology (ART) registry was cross-linked with the Danish Medical Birth registry to identify live births. The primary outcome of interest was births following fertility treatment.Our sample comprised pregnancies from asthmatic mothers (n=932, described as "cases") and non-asthmatic mothers (n=2757, described as "controls"), with 12% (n=114) and 8% (n=212), respectively, having had fertility treatment (OR 1.67, 95% CI 1.32-2.13; p<0.001). This association remained statistically significant after adjusting for confounders, including body mass index (OR 1.31, 95% CI 1.00-1.70; p=0.047). In women ≥35â years, 25% of cases (n=63) and 13% of controls (n=82) received fertility treatment (OR 2.12, 95% CI 1.47-3.07; p<0.001), which also remained statistically significant after adjusting for confounders (OR 1.65, 95% CI 1.11-2.46; p=0.013).A higher proportion of the births from asthmatic mothers involved fertility treatment compared to non-asthmatic mothers, not least among women aged ≥35â years.
Assuntos
Asma/terapia , Infertilidade Feminina/terapia , Adulto , Asma/complicações , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Fertilidade , Humanos , Infertilidade Feminina/complicações , Estilo de Vida , Nascido Vivo , Óxido Nítrico/metabolismo , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Sistema de Registros , Técnicas de Reprodução AssistidaRESUMO
BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in severe acute and chronic medical conditions and has been associated with short-term mortality. The role of suPAR in predicting risk of death following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has never been studied. We hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure. METHODS: This retrospective cohort study from a university hospital in the Capital Region of Denmark included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis, who had plasma suPAR measured at the time of admission between November 18th, 2013 to September 30th, 2015 and followed until December 31st, 2015. Primary outcomes were 30- and 90-days all-cause mortality. Association of suPAR and mortality was investigated by Cox regression analyses adjusted for age, sex, CRP values and Charlson comorbidity index. RESULTS: For patients with AECOPD or underlying COPD, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P < 0.0001). Increasing suPAR levels independently predicted 30-day mortality in patients with COPD with a hazard ratio of 2.0 (95% CI 1.7-2.4) but not respiratory failure. CONCLUSIONS: In this large group of acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality. The study supports the value of suPAR as a marker of poor prognosis.
Assuntos
Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/mortalidade , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: Asthma has traditionally been regarded as a contraindication to self-contained underwater breathing apparatus (SCUBA) diving, although large numbers of patients with asthma dive. The aim of the review is to provide an update on current knowledge on potential disease-related hazards in SCUBA divers with asthma. METHODS: Systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven studies met the criteria for inclusion in the review (comprising a total of 560 subjects). Five studies reported an increased risk for developing diving-related injuries in divers with asthma, based on case reports (n = 1), case history combined with objective assessment (n = 1), and dives and/or simulated dives (n = 3). The remaining studies (n = 2) were based on self-reported diving habits in divers suffering from asthma, obtained from anonymous questionnaires in diving magazines, reported no diving-related injuries among respondents. CONCLUSION: Due to limited evidence it is difficult to draw valid conclusions, but there are indications that recreational divers with asthma may be at increased risk for diving-related injuries compared to non-asthmatic divers. However, it is of at most importance to obtain further evidence from large-scale, well-designed studies.
Assuntos
Asma/epidemiologia , Mergulho/efeitos adversos , Humanos , Recreação , Fatores de RiscoRESUMO
RATIONALE: Physical activity enhances uptake of air pollutants in the lung, possibly augmenting their harmful effects on chronic lung disease during exercise. OBJECTIVES: To examine whether benefits of physical activity with respect to the risk of asthma and chronic obstructive pulmonary disease (COPD) are moderated by exposure to high air pollution levels in an urban setting. METHODS: A total of 53,113 subjects (50-65 yr) from the Danish Diet, Cancer, and Health cohort reported physical activity at recruitment (1993-1997) and were followed until 2013 in the National Patient Register for incident hospitalizations for asthma and COPD. Levels of nitrogen dioxide (NO2) were estimated at subject residences at the time of recruitment. We used Cox regression to associate physical activities and NO2 (high/medium/low) with asthma and COPD, and then introduced an interaction term between each physical activity and NO2. MEASUREMENTS AND MAIN RESULTS: A total of 1,151 subjects were hospitalized for asthma and 3,225 for COPD during 16 years. We found inverse associations of participation in sports (hazard ratio [95% confidence interval]: 0.85 [0.75-0.96]) and cycling (0.85 [0.75-0.96]) with incident asthma, and of participation in sports (0.82 [0.77-0.89]), cycling (0.81 [0.76-0.87]), gardening (0.88 [0.81-0.94]), and walking (0.85 [0.75-0.95]) with incident COPD admissions. We found positive associations between NO2 and incident asthma (1.23 [1.04-1.47]) and COPD (1.15 [1.03-1.27]) hospitalizations (comparing ≥21.0 µg/m3 to <14.3 µg/m3). We found no interaction between associations of any physical activity and NO2 on incident asthma or COPD hospitalizations. CONCLUSIONS: Increased exposure to air pollution during exercise does not outweigh beneficial effects of physical activity on the risk of asthma and COPD.
RESUMO
PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness, and more recently it has been shown that weight reduction following bariatric surgery has positive impact on small airway function, systemic inflammation and bronchial inflammation in this group of patients, which may explain the observed improvements in symptom control and lung function. SUMMARY: Weight reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma.
Assuntos
Asma/complicações , Asma/terapia , Obesidade/complicações , Asma/fisiopatologia , Humanos , Qualidade de Vida , Testes de Função Respiratória , Fatores de Risco , Redução de PesoRESUMO
BACKGROUND: Maintenance therapy with oral corticosteroid (OCS) is used, although not based on evidence, for patients with severe asthma, but OCS is associated with serious adverse effects; therefore, management strategies aimed at steroid sparing are important. OBJECTIVE: To provide an update on the evidence for OCS-sparing strategies in adults with severe asthma. METHODS: A systematic literature review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 21 studies (which comprised 3060 subjects) were included. Of the nonbiologic oral steroidsparing strategies (n = 5), the following lowered the OCS dose: Internet-based tapering strategy (44% reduction in OCS dose), inhaled corticosteroids (mometasone furoate [mean daily OCS dose reduction of 39% and 31% in patients treated with 800 mcg/day and 1600 mcg/day, respectively] and ciclesonide [OCS dose reduction of 47% and 63% in patients treated with 640 mcg/day and 1.280 mcg/day, respectively]), and methotrexate (OCS dose reduction of 55%). Of the biologic oral steroidtapering strategies (16 studies) the following agents lowered the OCS dose: cyclosporin A (62% reduction in OCS dose), masitinib (78% reduction in OCS dose), mepolizumab (50%83% reduction in OCS dose), and omalizumab (30%64% of enrolled patients achieved a reduction in OCS dose, and one study reported a dose reduction of 45%). CONCLUSIONS: In adults with severe asthma, several corticosteroid-sparing interventions were shown to be effective in reducing systemic steroid exposure, not least in studies of add-on biologic therapy. However, based on the available studies, ciclesonide, based on the low potential for systemic effect, especially seems to be a good candidate for reducing steroid exposure in these patients before possible initiation of biologic therapy.
Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Administração por Inalação , Administração Oral , Corticosteroides/administração & dosagem , Adulto , Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Biomarcadores , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Objectives: Endothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea. Methods: A prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model. Results: We did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: -3.9-12.9, p = 0.30), TM: 2.2 mL/year (95% CI: -6.0-10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: -6.0-14.2, p = 0.42), TM: 1.4 mL/year (95% CI: -8.3-11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89-2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65-1.71, p = 0.26). Conclusion: We did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.
RESUMO
BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.
RESUMO
Asthma and infertility are the most common disorders among women of reproductive age. Time to pregnancy is prolonged in women with asthma, and importantly, age seems to be a more important risk factor regarding fertility in women with asthma compared to women without asthma. Some data have shown a higher frequency of miscarriages in women with asthma, although the data are conflicting on this issue as studies have observed no association between asthma and pregnancy loss. Furthermore, studies have shown no negative effect of asthma on the total number of offspring. Pregnancy may, thus, have a significant impact on women with asthma, as well as on their offspring. The age of the women has an important impact on ability to conceive, but also for the pregnancy itself, with higher risk of uncontrolled asthma as well as asthma exacerbations with increasing age. Well-controlled asthma decreases the risk of maternal and fetal complications, while poorly controlled and undertreated asthma is associated with a range of risks for both mother and fetus. Asthma treatment should follow the general guidelines for asthma therapy, irrespective of pregnancy status, including treatment with inhaled corticosteroids, ß2-agonists and muscarinic antagonists. Targeted treatment with biologics for severe asthma seems to be without important adverse effects. The use of systemic corticosteroids may be associated with adverse events during the first trimester; however, an exacerbation with the associated risk of hypoxaemia is worse for the fetus. Best possible asthma control may be achieved using repeated measurements of fractional exhaled nitric oxide (F ENO), as the use of F ENO compared with symptoms registration only has been shown to reduce exacerbation rate. In conclusion, women with asthma should be encouraged to conceive at an early age, might experience miscarriages, but the number of offspring are the same as in women without asthma. Well treated asthma is important for the well-being of both the mother and the unborn fetus.
RESUMO
Rationale: Moderate to severe asthma is associated with impaired asthma control and quality of life (QoL) despite access to specialist care and modern pharmacotherapy. Breathing exercises (BrEX) improve QoL in incompletely controlled mild asthma, but impact in moderate to severe asthma is unknown. Objectives: To investigate the effectiveness of BrEX as adjuvant treatment on QoL in patients with uncontrolled moderate to severe asthma. Methods: Adult patients with incompletely controlled asthma attending respiratory specialist clinics were randomized to usual specialist care (UC) or UC and BrEX (UC + BrEX) with three individual physiotherapist-delivered sessions and home exercises. Primary outcome was asthma-related QoL (Mini-Asthma Quality of Life Questionnaire [Mini-AQLQ]) at 6 months on the basis of intention-to-treat analysis. Secondary outcomes: Mini-AQLQ at 12 months, lung function, 6-minute-walk test, physical activity level, Nijmegen Questionnaire, Hospital Anxiety and Depression Scale, and adverse events. Repeated-measures mixed-effects models were used to analyze data. Poisson regression models were used to analyze adverse event incidence rate ratio. Results: A total of 193 participants were allocated to UC + BrEX (n = 94) or UC (n = 99). UC + BrEX was superior in the primary outcome (adjusted mean change difference, 0.35; 95% confidence interval [CI], 0.07 to 0.62). Superiority in Mini-AQLQ was sustained at 12 months (0.38; 95% CI, 0.12 to 0.65). A minor improvement in Hospital Anxiety and Depression Scale depression score at 6 months favoring UC + BrEX (-0.90; 95% CI, -1.67 to -0.14) was observed. Asthma-related adverse events occurred similarly in UC + BrEX and UC participants: 14.9% versus 18.1% (P = 0.38). Conclusions: BrEX as add-on to usual care improve asthma-related QoL in incompletely controlled asthma regardless of severity and with no evidence of harm. Clinical trial registered with www.clinicaltrials.gov (NCT03127059).
Assuntos
Asma , Qualidade de Vida , Adulto , Asma/terapia , Exercícios Respiratórios , Terapia por Exercício , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage. METHODS: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). RESULTS: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. DISCUSSION: Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.
Assuntos
Infecções por Pseudomonas , Doença Pulmonar Obstrutiva Crônica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/microbiologia , Sistema Respiratório/microbiologiaRESUMO
AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.
Assuntos
COVID-19 , Insuficiência Cardíaca , Disfunção Ventricular Direita , Idoso , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Função Ventricular DireitaRESUMO
The role of statins on the disease course of COPD is controversial. Observational studies have shown a reduction in mortality and exacerbations, but results of randomised clinical trials (RCTs) of statin treatment and its effect on adverse outcomes are conflicting. Recent meta-analyses suggest the need for further RCTs including COPD patients both with and without concurrent cardiovascular disease (CVD). As there are no known detrimental effects of statins in COPD patients, we conclude in this review, that statins should be prescribed more frequently in these patients due to the common co-morbidity with CVD.
Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inflamação/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
Introduction: The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. Methods: This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein. Results: suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/µL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/µL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/µL) group. Conclusion: In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.