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1.
Artigo em Inglês | MEDLINE | ID: mdl-38701495

RESUMO

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/).

2.
Allergy ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38923444

RESUMO

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

3.
Ann Allergy Asthma Immunol ; 132(5): 610-622.e7, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151100

RESUMO

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR 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 (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 (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).


Assuntos
Antiasmáticos , Asma , Humanos , Asma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Antiasmáticos/uso terapêutico , Estudos Longitudinais , Resultado do Tratamento , Índice de Gravidade de Doença , Corticosteroides/uso terapêutico , Sistema de Registros , Idoso
4.
BMC Pulm Med ; 24(1): 6, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166965

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) frequently coexists with other chronic diseases, namely comorbidities. They negatively impact prognosis, exacerbations and quality of life in COPD patients. However, no studies have been performed to explore the impact of these comorbidities on COPD clinical control criteria. RESEARCH QUESTION: Determine the relationship between individualized comorbidities and COPD clinical control criteria. STUDY DESIGN AND METHODS: Observational, multicenter, cross-sectional study performed in Spain involving 4801 patients with severe COPD (< 50 predicted forced expiratory volume in the first second [FEV1%]). Clinical control criteria were defined by the combination of COPD assessment test (CAT) scores (≤16 vs ≥17) and exacerbations in the previous three months (none vs ≥1). Binary logistic regression adjusted by age and FEV1% was performed to identify comorbidities potentially associated with the lack of control of COPD. Secondary endpoints were the relationship between individualized comorbidities with COPD assessment test and exacerbations within the last three months. RESULTS: Most frequent comorbidities were arterial hypertension (51.2%), dyslipidemia (36.0%), diabetes (24.9%), obstructive sleep apnea-hypopnea syndrome (14.9%), anxiety (14.1%), heart failure (11.6%), depression (11.8%), atrial fibrillation (11.5%), peripheral arterial vascular disease (10.4%) and ischemic heart disease (10.1%). After age and FEV1% adjustment, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; all p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; all p < 0.001), sleep disorders (p < 0.0001), anemia (p = 0.015) and gastroesophageal reflux (p < 0.0001). These comorbidities were also related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are frequent in patients with severe COPD, negatively impacting COPD clinical control criteria. They are related to health-related quality of life measured by the COPD assessment test. Our results suggest that comorbidities should be investigated and treated in these patients to improve their clinical control. TAKE-HOME POINTS: Study question: What is the impact of comorbidities on COPD clinical control criteria? RESULTS: Among 4801 patients with severe COPD (27.5% controlled and 72.5% uncontrolled), after adjustment by age and FEV1%, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; p < 0.001), obstructive sleep apnea-hypopnea syndrome (p < 0.0001), anaemia (p = 0.015) and gastroesophageal reflux (p < 0.0001), which were related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are related to health-related quality of life measured by the COPD assessment test scores and history of exacerbations in the previous three months.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Insuficiência Cardíaca , Hipertensão , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Estudos Transversais , Volume Expiratório Forçado , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/complicações , Hipertensão/complicações , Obesidade Abdominal/complicações , Doenças Vasculares Periféricas/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Apneia Obstrutiva do Sono/complicações
5.
Allergy ; 78(7): 1934-1948, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36929509

RESUMO

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Asma/induzido quimicamente , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Estudos Prospectivos
6.
Analyst ; 148(19): 4837-4843, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37622408

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) is a pathogen that persistently colonizes the respiratory tract of patients with chronic lung diseases. The risk of acquiring a chronic P. aeruginosa infection can be minimized by rapidly detecting the pathogen in the patient's airways and promptly administrating adequate antibiotics. However, the rapid detection of P. aeruginosa in the lungs involves the analysis of sputum, which is a highly complex matrix that is not always available. Here, we propose an alternative diagnosis based on analyzing breath aerosols. In this approach, nanoparticle immunosensors identify bacteria adhered to the polypropylene layer of a surgical facemask that was previously worn by the patient. A polypropylene processing protocol was optimized to ensure the efficient capture and analysis of the target pathogen. The proposed analytical platform has a theoretical limit of detection of 105 CFU mL-1 in aerosolized mock samples, and a dynamic range between 105 and 108 CFU mL-1. When tested with facemasks worn by patients, the biosensors were able to detect chronic and acute P. aeruginosa lung infections, and to differentiate them from respiratory infections caused by other pathogens. The results shown here pave the way to diagnose Pseudomonas infections at the bedside, as well as to identify the progress from chronic to acute infection.


Assuntos
Técnicas Biossensoriais , Fibrose Cística , Infecções por Pseudomonas , Humanos , Pseudomonas aeruginosa , Máscaras/efeitos adversos , Polipropilenos , Imunoensaio , Pulmão , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/microbiologia
7.
Int J Mol Sci ; 24(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240045

RESUMO

COPD is a leading cause of mortality and morbidity worldwide and is associated with a high socioeconomic burden. Current treatment includes the use of inhaled corticosteroids and bronchodilators, which can help to improve symptoms and reduce exacerbations; however, there is no solution for restoring lung function and the emphysema caused by loss of the alveolar tissue. Moreover, exacerbations accelerate progression and challenge even more the management of COPD. Mechanisms of inflammation in COPD have been investigated over the past years, thus opening new avenues to develop novel targeted-directed therapies. Special attention has been paid to IL-33 and its receptor ST2, as they have been found to mediate immune responses and alveolar damage, and their expression is upregulated in COPD patients, which correlates with disease progression. Here we summarize the current knowledge on the IL-33/ST2 pathway and its involvement in COPD, with a special focus on developed antibodies and the ongoing clinical trials using anti-IL-33 and anti-ST2 strategies in COPD patients.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Enfisema Pulmonar/tratamento farmacológico , Progressão da Doença
8.
Int J Mol Sci ; 24(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37762552

RESUMO

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

9.
Respir Res ; 23(1): 49, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248041

RESUMO

BACKGROUND: Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD. METHODS: EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed. RESULTS: A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/µL (SD: 125) vs. 160 cells/µL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC. CONCLUSIONS: This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.


Assuntos
Eosinofilia/epidemiologia , Eosinófilos/patologia , Vigilância da População , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Eosinofilia/sangue , Eosinofilia/etiologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Espanha/epidemiologia
10.
Allergy ; 77(1): 150-161, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33978983

RESUMO

BACKGROUND: Clinically meaningful improvement in the Sino-Nasal Outcome Test-22 (SNOT-22) was observed in patients with severe, eosinophilic asthma, and nasal polyposis (NP) treated with benralizumab in the ANDHI trial. A post hoc assessment of the effects of benralizumab on SNOT-22 response and asthma efficacy measures in these patients was conducted for further characterization of the efficacy and safety of benralizumab for patients with severe asthma and NP. METHODS: Adults with severe, eosinophilic asthma who had experienced ≥2 prior-year exacerbations despite high-dosage inhaled corticosteroid plus additional controller[s] were randomized to 24 weeks of benralizumab or placebo. Patients with physician-diagnosed chronic rhinosinusitis with NP of any severity ongoing at baseline who consented to participate were included in the current ANDHI NP substudy population. Effect on NP symptoms was assessed by the SNOT-22, with an improvement of at least 8.9 defined as clinically significant (responder). Effects on chronic asthma outcomes were assessed by means of annualized asthma exacerbation rate (AER), St. George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in one second (FEV1 ), and Asthma Control Questionnaire-6 (ACQ-6). All p-values were nominal. RESULTS: Of the ANDHI population (n = 656), 23% (n = 153) participated in the NP substudy (n = 96 benralizumab; n = 57 placebo). Patients were 50% female, with mean age of 53 years, had prior-year AER = 3.3; mean pre-bronchodilator FEV1  = 55% predicted; and median blood eosinophil count â€‹= 510 cells/µl. For patients with high baseline SNOT-22 scores (>30), benralizumab treatment improved symptoms of NP as measured by SNOT-22 from baseline to Week 24 compared with placebo (Week 24: -10.44 [p = .0176]). Percentage of responders to SNOT-22 was greater for benralizumab vs. placebo (71.3% vs. 45.5%; p = .0036), and effect was enhanced for patients with high baseline SNOT-22 scores (>30). A 69% reduction vs. placebo in annualized AER (0.77 vs. 2.47; p < .0001) and greater clinically meaningful improvements from baseline in SGRQ total score (-16.7), FEV1 (+0.32 L), and ACQ-6 (-0.88) were observed (p < .0001). Benralizumab was well-tolerated. Frequency of adverse events (AEs) was similar for benralizumab (76.0%) and placebo (73.7%) groups. Most common AEs (frequency ≥5%) reported at a greater frequency in benralizumab vs. placebo included headache, sinusitis, pyrexia, and influenza. CONCLUSIONS: These substudy data from ANDHI demonstrated the efficacy profile of benralizumab for patients with severe, eosinophilic asthma and NP, with improvement in SNOT-22 and asthma outcomes.


Assuntos
Antiasmáticos , Asma , Eosinofilia Pulmonar , Adulto , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/induzido quimicamente , Asma/diagnóstico , Asma/tratamento farmacológico , Progressão da Doença , Método Duplo-Cego , Eosinófilos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Eosinofilia Pulmonar/tratamento farmacológico , Resultado do Tratamento
11.
Int J Mol Sci ; 23(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897707

RESUMO

Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.


Assuntos
Infecções por Pseudomonas , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/efeitos adversos , Budesonida/efeitos adversos , Humanos , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptor 2 Toll-Like
12.
Respir Res ; 22(1): 36, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541356

RESUMO

BACKGROUND: Control in COPD is a dynamic concept that can reflect changes in patients' clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences. METHODS: We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis. RESULTS: 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394-3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern. CONCLUSIONS: The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results. TRIAL REGISTRATION: Clinical Trials.gov: identifier NCT01122758.


Assuntos
Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Espanha/epidemiologia
13.
BMC Med Res Methodol ; 20(1): 212, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32819285

RESUMO

BACKGROUND: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. METHODS: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. CONCLUSIONS: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.


Assuntos
Asma , Adolescente , Adulto , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Humanos , Sistema de Registros
15.
BMC Pulm Med ; 19(1): 112, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234826

RESUMO

BACKGROUND: The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear. METHODS: Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing. The microbiome composition was analysed with QIIME. RESULTS: We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera. CONCLUSION: The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.


Assuntos
Eosinófilos/citologia , Microbiota , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/microbiologia , Sistema Respiratório/microbiologia , Idoso , Estudos Transversais , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Contagem de Leucócitos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença , Escarro/citologia , Escarro/microbiologia
16.
COPD ; 16(1): 8-17, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30870059

RESUMO

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up.


Assuntos
Progressão da Doença , Dispneia/etiologia , Pneumopatias Obstrutivas/mortalidade , Pneumopatias Obstrutivas/fisiopatologia , Idoso , Área Sob a Curva , Calibragem , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Pneumopatias Obstrutivas/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco/métodos , Exacerbação dos Sintomas , Fatores de Tempo
17.
Eur Respir J ; 52(6)2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30309976

RESUMO

There is increasing interest in the origins of chronic obstructive pulmonary disease (COPD), as it is envisaged that preventive efforts and treatment can modify its clinical course. The concept of early COPD is not new, but it has recently regained interest, given new population data, recent cellular and molecular advances and insights from clinical trials. To date, many knowledge gaps in the nature of early COPD still exist, mainly because COPD has always been considered a disease of the elderly, and little attention has been paid to the pathological changes occurring in the lungs of individuals at risk before they develop clinically evident COPD. Future studies should focus on identifying early pathological manifestations of COPD in order to prevent its progression in susceptible individuals. In this review, we aim to summarise what is known on early COPD, from the epidemiological, cellular and clinical perspectives.


Assuntos
Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idade de Início , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco
18.
BMC Med ; 16(1): 33, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29495970

RESUMO

BACKGROUND: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD. METHODS: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores. RESULTS: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUCADO - AUCBODE = 0.015 [95% confidence interval (CI) = -0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated - AUCBODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency. CONCLUSIONS: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença
19.
Respir Res ; 19(1): 118, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29903047

RESUMO

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-ß, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils.


Assuntos
Medula Óssea/imunologia , Medula Óssea/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Estudos de Coortes , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Mapas de Interação de Proteínas/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar/imunologia , Fumar/metabolismo , Fumar/patologia
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