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1.
Clin Med (Lond) ; 23(5): 467-477, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37775167

RESUMEN

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.


Asunto(s)
Bronquiectasia , COVID-19 , Fibrosis Pulmonar , Adulto , Humanos , Fibrosis Pulmonar/diagnóstico por imagen , COVID-19/diagnóstico por imagen , Estudios Retrospectivos , Estudios de Seguimiento , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Progresión de la Enfermedad , Disnea
2.
Future Healthc J ; 9(3): 335-342, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36561827

RESUMEN

In response to the first COVID-19 surge in 2020, secondary care outpatient services were rapidly reconfigured to provide specialist review for disease sequelae. At our institution, comprising hospitals across three sites in London, we initially implemented a COVID-19 follow-up pathway that was in line with expert opinion at the time but more intensive than initial clinical guidelines suggested. We retrospectively evaluated the resource requirements for this service, which supported 526 patients from April 2020 to October 2020. At the 6-week review, 193/403 (47.9%) patients reported persistent breathlessness, 46/336 (13.7%) desaturated on exercise testing, 167/403 (41.4%) were discharged from COVID-19-related secondary care services and 190/403 (47.1%) needed 12-week follow-up. At the 12-week review, 113/309 (36.6%) patients reported persistent breathlessness, 30/266 (11.3%) desaturated on exercise testing and 150/309 (48.5%) were discharged from COVID-19-related secondary care services. Referrals were generated to multiple medical specialties, particularly respiratory subspecialties. Our analysis allowed us to justify rationalising and streamlining provisions for subsequent COVID-19 waves while reassured that opportunities for early intervention were not being missed.

3.
JCI Insight ; 7(15)2022 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-35763349

RESUMEN

Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared with control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and is further induced by a viral mimetic, whereas IL-36Ra is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ, thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, which was inhibited by exogenous IL-36Ra. The use of a therapeutic antibody that inhibits binding to the IL-36R attenuated IL-36γ-driven inflammation and cellular crosstalk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and have shown that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising therapeutic strategy in the treatment of COPD.


Asunto(s)
Interleucina-1 , Enfermedad Pulmonar Obstructiva Crónica , Receptores de Interleucina/agonistas , Citocinas/metabolismo , Humanos , Inflamación/metabolismo , Interleucina-1/metabolismo , Interleucinas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
4.
Postgrad Med J ; 98(1159): 328-330, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34344700

RESUMEN

The COVID-19 pandemic has had a significant impact on postgraduate medical training across all specialties. Although some traditional learning opportunities have been curtailed, there have been numerous examples of highly valuable educational experiences that have arisen during this time. Here, from a trainee perspective, we consider the educational merits of the re-emergence of 'firm-based' teams, new online learning opportunities, use of digital technologies and the rise of telephone clinics and new COVID-19 clinical services. As health services continue to recover from surges in COVID-19 cases, it is important to reflect on and recognise the value of these educational experiences so that helpful elements can be retained and embedded into training programmes for the benefit of both trainees and patients.


Asunto(s)
COVID-19 , Educación a Distancia , COVID-19/epidemiología , Humanos , Aprendizaje , Pandemias
5.
J Asthma Allergy ; 13: 429-437, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33116651

RESUMEN

BACKGROUND: Guidelines recommend that asthma treatment should be stepped down to the minimally effective dose that achieves symptom control to prevent medication side effects and reduce unnecessary costs. Little is known about the practice of stepping down and the challenges in primary care, where most asthma patients are managed. OBJECTIVE: To explore views, experiences, barriers and ideas, of doctors, nurses and pharmacists working in primary care, related to step down of asthma medication. METHODS: Primary care practitioners from across the UK participated in a survey and/or semi-structured interview. Questions explored four main areas: how asthma medication is reviewed, views on asthma guidelines, perceived barriers faced by healthcare workers and facilitators of stepping down. Qualitative content analysis enabled data coding of interview transcripts to identify major themes. RESULTS: A total of 274 participants responded to the survey, 29 participated in an interview (12 doctors, 9 nurses, and 8 pharmacists), working in GP practices from across the UK. Nearly half of the survey participants infrequently step down asthma medication (doctors=42.7%, nurses=46.3%). Four major themes related to barriers to stepping down were (i) lack of awareness of the need to step down, (ii) inertia to step down, driven by low confidence in ability, fear of consequences, and concern for who is responsible for stepping down, (iii) self-efficacy of ability to step down, influenced by lack of clear, applied guidance and limited training, and (iv) feasibility of step down, driven by a lack of systematic acceptance of stepping down and time. Strategies proposed to reduce overtreatment included education and training, improved gathering of evidence and guidance, and integrating step down into routine asthma care. CONCLUSION: Failure to implement this guideline recommendation into everyday asthma management is influenced by several contributing factors. Future directions should include addressing evidence gaps, implementing clear and practical guidance, integration of step-down assessment into the asthma review, and education of professionals and patients.

6.
Future Healthc J ; 7(3): e88-e92, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33094266

RESUMEN

Integration of primary and secondary care for the management of respiratory disease is a long-held ambition. Here, we describe how respiratory specialists at a large NHS trust, working with primary care clinicians in the area, set up a GP hotline and respiratory support service in response to the COVID-19 pandemic, with the aim of enhancing delivery of care to patients in this unprecedented time. Working across traditional organisational boundaries in this way confers benefits to patients and clinicians, illustrating the value of new, integrated models of care.

7.
Int J Chron Obstruct Pulmon Dis ; 15: 1377-1390, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32606647

RESUMEN

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD. Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like. Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required. Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.


Asunto(s)
Osteoporosis , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Consenso , Humanos , Osteoporosis/diagnóstico , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Participación del Paciente , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Factores de Riesgo , Reino Unido/epidemiología
8.
Am J Respir Crit Care Med ; 202(4): 549-557, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32267724

RESUMEN

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.Methods: In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.Measurements and Main Results: Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (n = 72) or placebo (n = 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68; P = 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).


Asunto(s)
Ciprofloxacina/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Anciano , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Retratamiento , Factores de Tiempo , Resultado del Tratamiento
9.
ERJ Open Res ; 5(2)2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31249841

RESUMEN

RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia are two of the most common reasons for acute hospital admissions. Acute exacerbations and pneumonia present with similar symptoms in COPD patients, representing a diagnostic challenge with a significant impact on patient outcomes. The objectives of this study were to compare the prevalence of radiographic consolidation with the discharge diagnoses of hospitalised COPD patients. METHODS: COPD patients admitted to three UK hospitals over a 3-year period were identified. Participants were included if they were admitted with an acute respiratory illness, COPD was confirmed by spirometry and a chest radiograph was performed within 24 h of admission. Pneumonia was defined as consolidation on chest radiograph reviewed by two independent observers. RESULTS: There were 941 admissions in 621 patients included in the final analysis. In 235 admissions, consolidation was present on chest radiography and there were 706 admissions without consolidation. Of the 235 admissions with consolidation, only 42.9% had a discharge diagnosis of pneumonia; 90.7% of patients without consolidation had a discharge diagnosis of COPD exacerbation. The presence of consolidation was associated with increased rate of high-dependency care admission, increased mortality and prolonged length of stay. Inhaled corticosteroid use was associated with recurrent pneumonia. CONCLUSIONS: Pneumonia is underdiagnosed in patients with COPD. Radiographic consolidation is associated with worse outcomes and prolonged length of stay. Incorrect diagnosis could result in inappropriate use of inhaled corticosteroids. Future guidelines should specifically address the diagnosis and management of pneumonia in COPD.

10.
Artículo en Inglés | MEDLINE | ID: mdl-31114182

RESUMEN

Purpose: COPD patients often do not report acute exacerbations to healthcare providers - unreported exacerbations. It is not known whether variances in symptoms, airway obstruction, aetiology and inflammatory responses account for differences in reporting of COPD exacerbations. The aims of the study were to compare symptoms, lung function changes, aetiology and inflammatory markers between exacerbations that were reported to healthcare providers or treated, with those that were unreported and untreated. Patients and methods: We recruited a cohort of COPD patients and collected clinical data and blood and airway samples when stable and during acute exacerbations. Virological and bacterial analyses were carried out and inflammatory markers measured. Results: We found no differences in symptoms, lung function, incidence of infection and inflammatory markers between reported and unreported exacerbations. Subjects who reported all exacerbations had higher BODE scores, lower FEV1 and more exacerbations compared with those who did not. Conclusion: The failure to report exacerbations is not related to the severity, aetiology or inflammatory profile of the exacerbation. Patients with less severe COPD and less frequent exacerbations are less likely to report exacerbations. The decision to report an exacerbation is not an objective marker of exacerbation severity and therefore studies that do not count unreported exacerbations will underestimate the frequency of clinically significant exacerbations. A better understanding of the factors that determine non-reporting of exacerbations is required to improve exacerbation reporting. Trial registration: ClinicalTrials.gov Identifier: NCT01376830. Registered June 17, 2011.


Asunto(s)
Pulmón/fisiopatología , Neumonía/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Anciano , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Estado de Salud , Humanos , Mediadores de Inflamación/sangre , Pulmón/inmunología , Pulmón/microbiología , Pulmón/virología , Masculino , Persona de Mediana Edad , Neumonía/inmunología , Neumonía/fisiopatología , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/fisiopatología , Infecciones del Sistema Respiratorio/virología , Capacidad Vital
11.
J Allergy Clin Immunol ; 142(3): 815-823.e6, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29310905

RESUMEN

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear. OBJECTIVES: The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection. METHODS: We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function. Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations. Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined. RESULTS: Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD. In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values. There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load. Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro. CONCLUSIONS: Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations. Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD. This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD.


Asunto(s)
Glucosa/metabolismo , Infecciones por Pseudomonas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , Anciano , Carga Bacteriana , Líquido del Lavado Bronquioalveolar/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Líquido del Lavado Nasal/química , Infecciones por Picornaviridae/metabolismo , Infecciones por Picornaviridae/microbiología , Infecciones por Pseudomonas/microbiología , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Sistema Respiratorio/metabolismo , Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/microbiología , Fumar/metabolismo , Esputo/metabolismo , Carga Viral
12.
PLoS One ; 12(8): e0183864, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28859129

RESUMEN

Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.


Asunto(s)
Asma/inmunología , Quimiocina CX3CL1/inmunología , Interacciones Huésped-Patógeno , Leucocitos Mononucleares/inmunología , Infecciones por Picornaviridae/inmunología , Rhinovirus/inmunología , Adulto , Asma/complicaciones , Asma/genética , Asma/virología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virología , Estudios de Casos y Controles , Quimiocina CX3CL1/genética , Femenino , Expresión Génica , Humanos , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/virología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/patología , Macrófagos Alveolares/virología , Masculino , Infecciones por Picornaviridae/complicaciones , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/virología , ARN Mensajero/genética , ARN Mensajero/inmunología , Sistema Respiratorio/inmunología , Sistema Respiratorio/patología , Sistema Respiratorio/virología , Rhinovirus/crecimiento & desarrollo , Índice de Severidad de la Enfermedad
13.
COPD ; 13(5): 639-41, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26263193

RESUMEN

Over the last 10 years, community and hospital-based multidisciplinary teams (MDTs) have been set up for the management of patients with chronic obstructive pulmonary disease (COPD) in the UK. Meetings of the MDTs have become a regular occurrence, mostly on healthcare professionals' own initiatives. There are no standardized methods to conduct an MDT meeting, and although cancer MDT meetings are widely implemented, the value and purpose of COPD MDT meetings are less clear. Therefore, the aim of this study was to conduct a cross-sectional descriptive online survey to explore COPD MDT members' perceptions of the purpose and usefulness of MDT meetings, and to identify suggestions or requirements to improve the meetings. In total, we received 68 responses from 10 MDTs; six teams (n = 36 members) were located in London and four (n = 32 members) outside. Analysis of the replies by two independent researchers found that MDT meetings aim to optimise management and improve pathways for respiratory patients by improving communication between providers across settings and disciplines. Education of the MDT members also occurs with the aim of safer practice. Discussed patients are characterised by (multiple) co-morbidities, frequent exacerbations and admissions, social and mental health problems, unclear diagnosis and suboptimal responses to interventions. Members reported participating in a COPD MDT as very useful (74%) or useful (20%). Meetings could be improved by ensuring attendance through requirement in job plans, by clear documentation and sharing of derived plans with a wider audience including general practitioners and patients.


Asunto(s)
Actitud del Personal de Salud , Procesos de Grupo , Personal de Salud/psicología , Grupo de Atención al Paciente , Enfermedad Pulmonar Obstructiva Crónica/terapia , Comorbilidad , Estudios Transversales , Progresión de la Enfermedad , Humanos , Comunicación Interdisciplinaria , Trastornos Mentales/complicaciones , Participación del Paciente , Seguridad del Paciente , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Reino Unido
14.
Chest ; 149(1): 62-73, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25790167

RESUMEN

BACKGROUND: Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations. Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown. We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection. METHODS: Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus. Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages. In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured. RESULTS: Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD. O&NS markers correlated with virus load and inflammatory markers. Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress. Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation. Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines. CONCLUSIONS: O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations. Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.


Asunto(s)
Histona Desacetilasa 2/metabolismo , Estrés Oxidativo/fisiología , Infecciones por Picornaviridae/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Rhinovirus , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Nitrosación/fisiología , Infecciones por Picornaviridae/complicaciones , Esputo , Carga Viral
15.
PLoS One ; 10(2): e0116187, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25679218

RESUMEN

OBJECTIVES: We evaluated the impact of a COPD discharge care bundle on readmission rates following hospitalisation with an acute exacerbation. DESIGN: Interrupted time series analysis, comparing readmission rates for COPD exacerbations at nine trusts that introduced the bundle, to two comparison groups; (1) other NHS trusts in London and (2) all other NHS trusts in England. Care bundles were implemented at different times for different NHS trusts, ranging from October 2009 to April 2011. SETTING: Nine NHS acute trusts in the London, England. PARTICIPANTS: Patients aged 45 years and older admitted to an NHS acute hospital in England for acute exacerbation of COPD. Data come from Hospital Episode Statistics, April 2002 to March 2012. MAIN OUTCOME MEASURES: Annual trend readmission rates (and in total bed days) within 7, 28 and 90 days, before and after implementation. RESULTS: In hospitals introducing the bundle readmission rates were rising before implementation and falling afterwards (e.g. readmissions within 28 days +2.13% per annum (pa) pre and -5.32% pa post (p for difference in trends = 0.012)). Following implementation, readmission rates within 7 and 28 day were falling faster than among other trusts in London, although this was not statistically significant (e.g. readmissions within 28 days -4.6% pa vs. -3.2% pa, p = 0.44). Comparisons with a national control group were similar. CONCLUSIONS: The COPD discharge care bundle appeared to be associated with a reduction in readmission rate among hospitals using it. The significance of this is unclear because of changes to background trends in London and nationally.


Asunto(s)
Progresión de la Enfermedad , Análisis de Series de Tiempo Interrumpido , Admisión del Paciente , Paquetes de Atención al Paciente , Alta del Paciente/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Hospitales/estadística & datos numéricos , Humanos , Tiempo de Internación/estadística & datos numéricos , Londres/epidemiología , Persona de Mediana Edad , Programas Nacionales de Salud , Enfermedad Pulmonar Obstructiva Crónica/terapia , Estudios Retrospectivos
16.
J Surg Res ; 193(2): 704-12, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25282400

RESUMEN

BACKGROUND: Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury. METHODS: Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls. RESULTS: Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls. CONCLUSIONS: Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia.


Asunto(s)
Pruebas Respiratorias , Esofagectomía , Gastrectomía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/metabolismo , Ácido Acético/análisis , Acetona/análisis , Anciano , Butadienos/análisis , Femenino , Hemiterpenos/análisis , Humanos , Cianuro de Hidrógeno/análisis , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Estado Nutricional , Estrés Oxidativo , Pentanos/análisis , Periodo Perioperatorio , Estudios Prospectivos
17.
Lancet Respir Med ; 2(11): 919-932, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25240963

RESUMEN

Inhaled corticosteroids are widely used in chronic obstructive pulmonary disease (COPD) and, in combination with long-acting ß2 agonists, reduce exacerbations and improve lung function and quality of life. However, inhaled corticosteroids have been linked with an increased risk of pneumonia in individuals with COPD, but the magnitude of this risk, the effects of different preparations and doses, and the mechanisms of this effect remain unclear. Therefore, making informed clinical decisions--balancing the beneficial and adverse effects of inhaled corticosteroids in individuals with COPD--is difficult. Understanding of the mechanisms of increased pneumonia risk with inhaled corticosteroids is urgently needed to clarify their role in the management of COPD and to aid the development of new, safer therapies.


Asunto(s)
Corticoesteroides/efectos adversos , Neumonía/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/inmunología , Corticoesteroides/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Factores de Confusión Epidemiológicos , Humanos , Estudios Observacionales como Asunto , Neumonía/diagnóstico , Neumonía/prevención & control , Infecciones del Sistema Respiratorio/complicaciones , Factores de Riesgo
20.
COPD ; 10(1): 40-54, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23272667

RESUMEN

Earlier diagnosis of COPD is a major public health challenge as symptoms may be attributed to the normal consequences of aging. The optimum strategy for identifying patients with COPD remains to be determined. People aged 35 and over (n = 1896) on a GP practice register were randomised to either invitation or an opportunistic lung health check which included spirometry, quadriceps strength and MRC dyspnoea score. Then, 101 participants subsequently completed the General Practice Physical Activity Questionnaire. A total of 335 attended over a 15-week period; 156 were in the invitation group and 179 from the opportunist group. In 25 persons, spirometry was unsatisfactory or contraindicated. Spirometry was normal in 204(65.8%) and restrictive in 36(11.6%). 70(22.6%) had airflow obstruction, corresponding to Global Initiative for Chronic Lung Disease (GOLD) stages I-IV in 18(5.8%), 35(11.3%), 14(4.5%) and 3(1.0%), respectively. The opportunist group were significantly more likely to have airflow obstruction 30.1% vs 14.3% (p = 0.001). Breathlessness was reported commonly (40.5%) and quadriceps strength correlated significantly with MRC dyspnoea score independent of age, sex, pack-years smoked, fat-free mass and FEV(1) percent predicted. This relationship was also present in the subgroup of healthy participants (n = 143). 51.5% of participants screened were classified as "inactive" and this group were weaker and more breathless than those who were more active. Airflow obstruction was more common in those screened opportunistically. Breathlessness and inactivity are common in patients taking part in spirometry screening. Breathlessness is significantly associated with leg strength independent of spirometry and should be amenable to interventions to increase physical activity.


Asunto(s)
Disnea/diagnóstico , Tamizaje Masivo/métodos , Debilidad Muscular/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Adulto , Anciano , Análisis de Varianza , Estudios Transversales , Disnea/complicaciones , Femenino , Volumen Espiratorio Forzado , Medicina General , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Dinamómetro de Fuerza Muscular , Debilidad Muscular/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Músculo Cuádriceps/fisiopatología , Conducta Sedentaria , Fumar , Espirometría , Encuestas y Cuestionarios
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