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1.
BMJ Open Respir Res ; 11(1)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39222968

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is comprised of a heterogeneous group of pulmonary diseases. Oxygen therapy is used in patients with advanced lung disease; however, there are challenges associated with initiation of oxygen therapy specific to individuals with ILD. The key objectives of this study were to create a common understanding of the facilitators and barriers to oxygen therapy for patients with ILD, and healthcare professionals (HCP) caring for patients with ILD. METHODS: This qualitative study included 1 hour semistructured focus groups/interviews. An iterative and concurrent process was used for data collection and analysis to allow for supplementary development of themes and concepts generated. Data analysis used a three-phase approach: coding, categorising and development of themes. RESULTS: A total of 20 patients and/or caregivers and 31 HCP took part in 34 focus groups/interviews held over 3 months (November 2022-January 2023). Facilitators to oxygen therapy were identified including support from HCP and support groups, the perseverance and self-advocacy of patients, a straightforward administrative process and vendors/private industry that expedite access to oxygen therapy. There were also several barriers to accessing oxygen therapy for patients with ILD. The themes identified include rural disparity, testing requirements and qualifying for funding and the need for ILD-specific evidence base for oxygen therapy. CONCLUSION: Further research is needed to facilitate development of specific exertional oxygen criteria for patients with ILD, to create supports for oxygen use and monitoring and to enable providers to tailor therapy to patients. Oxygen therapy education for ILD should address the benefits and risks of oxygen therapy.


Assuntos
Grupos Focais , Doenças Pulmonares Intersticiais , Oxigenoterapia , Pesquisa Qualitativa , Humanos , Doenças Pulmonares Intersticiais/terapia , Oxigenoterapia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Acessibilidade aos Serviços de Saúde , Adulto , Cuidadores
2.
Cureus ; 15(12): e50738, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38111819

RESUMO

High-flow nasal cannula (HFNC) oxygen therapy is gaining traction globally as a treatment for respiratory failure. There are several physiological benefits, and there is a growing body of evidence showing improved quality of life and patient comfort with HFNC, both in acute and home settings. Due to the increased burden of long-term respiratory conditions such as chronic obstructive pulmonary disease (COPD) on healthcare systems worldwide, the role of ward-based and post-discharge interventions in the prevention of hospital readmissions is an area of increasing interest. In this narrative review, we outline the physiological effects of HFNC and assess its applications in both the hospital and home settings for acute and chronic respiratory failure. We also consider the evidence of non-invasive ventilation (NIV) versus HFNC in the hospital setting and the application of HFNC at home in stable hypercapnic respiratory failure to improve the quality of life and prevent readmissions. We also look at applications of HFNC in specific circumstances, such as the perioperative period, emergency department, and acute (mainly critical care) setting including in immunocompromised patients and palliative care.

3.
Int J Chron Obstruct Pulmon Dis ; 18: 2543-2553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022833

RESUMO

Background and Methods: Constant-minute-volume and constant-bolus devices serve as two different means of portable oxygen conservation. A prospective randomised crossover study was conducted in COPD GOLD IV patients to investigate the effect of these two devices on dyspnea, oxygenation and 6-minute walking test (6MWT) distance. The primary endpoint was the final operating level required (operating level range 1-5 for both devices) by either device to meet the success criteria for mobile oxygen therapy, as outlined in the British Thoracic Society guidelines (SpO2 ≥90% throughout 6MWT; ≥10% increase in walking distance from baseline; improvement in BORG of at least 1 point from baseline). Results: Twenty-five patients were enrolled in the study and randomly assigned to one of two sequences involving the use of each type of portable oxygen conservation device. 14 female, 67.9 years (±7.8); FEV1: 27.3%pred. (±8.4); PaO2 at rest without oxygen: 50.3mmHg (±5.9). For both systems, 24/25 patients (96%) were successfully recruited. The mean operating-level difference when success criteria were met was -0.58 in favor of the constant bolus device (95% CI: -0.88 to -0.28, P <0.001). Secondary endpoints (walking distance, respiratory rate and BORG dyspnea) showed no statistically significant or clinically relevant differences. An algorithm created especially for this study showed a high success rate in terms of titration for the required operating level. Conclusion: Both portable oxygen-conserving devices met the success criteria in 96% of patients in the 6MWT when they were titrated to the correct level. The constant-bolus device required a significantly lower operating level to achieve the success criteria, hereby reducing energy consumption. Individual titration of the respective device is recommended, which can be facilitated by the novel titration algorithm described here.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Cross-Over , Estudos Prospectivos , Oxigênio , Dispneia/diagnóstico , Dispneia/terapia , Caminhada
4.
BMJ Open Respir Res ; 10(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37419519

RESUMO

Many patients with fibrosing interstitial lung disease (fILD) will need to use supplemental oxygen (O2) to maintain normoxia at some point in their illness. If it is not needed at the time of diagnosis, then if fILD progresses-or if a comorbid condition like pulmonary hypertension develops-O2 will become necessary, often, initially, during exertion and all-too-often, eventually, at rest as well. But presumably, if all else remains stable, if fILD progression is halted or slowed, O2 needs follow in parallel. Despite perceived or unnoticed benefits of O2, and prescribers' good intentions to improve patients' sense of well-being, patients with fILD generally view O2 with frustration and fear, as it threatens their already-impaired quality of life. Because of how meaningful and impactful O2 is to the lives of patients with fILD, 'O2 need' is a critically important-and perhaps the most-patient-centred metric that should be considered for incorporation as an endpoint in therapeutic trials. It is unclear how this should be done, but in this paper, we offer some possible approaches that merit consideration.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Humanos , Oxigênio , Qualidade de Vida , Doenças Pulmonares Intersticiais/diagnóstico , Fibrose
5.
Pulm Ther ; 9(2): 255-270, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37093408

RESUMO

INTRODUCTION: The aim of this work is to evaluate whether the addition of home oxygen therapy (HOT) would reduce readmission in chronic obstructive pulmonary disease (COPD) patients. METHODS: PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following keywords "chronic obstructive pulmonary disease", the intervention "long-term oxygen therapy", and the outcome "readmission" combined with the AND operator. The Newcastle-Ottawa Scale and Jadad Scale were used for assessing the quality of cohort studies and clinical trials, respectively. A random-effects model was employed in this study after calculating the standard errors by 95% confidence intervals. The I2 statistic and Cochran's Q-test were used to measure heterogeneity. To address heterogeneity, subgroup analyses were carried out according to the length of LTOT, which was classified as "over 8 months" and "under 8 months". RESULTS: Seven studies were included in the analysis. In the pooled analysis, the RR [CI95%, p value], heterogeneity criteria for readmission reduced by 1.542 [1.284-1.851, < 0.001], I2 = 60%, and 1.693 [1.645-1.744, < 0.001], I2 = 60% for patients with a length of LTOT treatment under and above 8 months, respectively. A sensitivity analysis was conducted by systematically omitting each study, and it showed no influential studies. Egger's test indicated no publication bias (p = 0.64). CONCLUSIONS: Based on our results in this systematic review, long-tern oxygen therapy (LTOT) at home was associated with a significantly lower risk ratio of hospital readmission. However, the sample sizes in the studies necessitate larger RCTs to evaluate the effect of LTOT on readmission in COPD patients.

6.
Respir Med Case Rep ; 42: 101829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936868

RESUMO

RNF213 p.Arg4810Lys is linked to various vascular diseases, including pulmonary arterial hypertension (PAH); however, its pathogenesis remains unclear. Here, we report the unique features of two cases of severe PAH with this variant: one is the first reported case with stenosis of the thoracic and abdominal aorta, femoral arteries, and subclavian veins. Coexistence of severe and continuous eosinophilic inflammation, which has been suspected to be implicated in the pathogenesis of PAH in previous fundamental studies, was also present in both cases. Further studies are needed to clarify the pathogenetic mechanisms in vascular lesions with this variant.

7.
Thorax ; 78(6): 596-605, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36635039

RESUMO

BACKGROUND: This review aims to synthesise available evidence on the prevalence of chronic obstructive pulmonary disease (COPD), associated risk factors, hospitalisations and COPD readmissions in Africa. METHOD: Using the Met-Analyses and Systematic Reviews of Observational Studies guideline, electronic databases were searched from inception to 1 October 2021. The quality of studies was assessed using the Newcastle-Ottawa Scale. Evidence from retrieved articles was synthesised, and a random-effect model meta-analysis was conducted. The protocol was registered on PROSPERO. RESULTS: Thirty-nine studies met the inclusion criteria, with 13 included in the meta-analysis. The prevalence of COPD varied between the Global Initiative for Chronic Obstructive Lung Disease (2%-24%), American Thoracic Society/European Respiratory Society (1%-17%) and Medical Research Council chronic bronchitis (2%-11%) criteria, respectively. Increasing age, wheezing and asthma were consistent risk factors for COPD from studies included in the narrative synthesis. Our meta-analysis indicated that prior tuberculosis ((OR 5.98, 95% CI 4.18 to 8.56), smoking (OR 2.80, 95% CI: 2.19 to 3.59) and use of biomass fuel (OR 1.52, 95% CI: 1.39 to 1.67)) were significant risk factors for COPD. Long-term oxygen therapy (HR 4.97, 95% CI (1.04 to 23.74)) and frequent hospitalisation (≥3 per year) (HR 11.48, 95% CI (1.31 to 100.79)) were risk factors associated with 30-day COPD readmission. CONCLUSION: This study not only highlights specific risk factors for COPD risk in Africa but also demonstrates the paucity and absence of research in several countries in a continent with substantial COPD-related mortality. Our findings contribute towards the development of evidence-based clinical guidelines for COPD in Africa.PROSPERO registration numberCRD42020210581.


Assuntos
Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Hospitalização , Fatores de Risco , Fumar , Qualidade de Vida
8.
J Gen Intern Med ; 38(11): 2560-2567, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36697930

RESUMO

BACKGROUND: Individuals prescribed long-term opioid therapy (LTOT) have increased risk of readmission and death after hospital discharge. The risk of opioid overdose during the immediate post-discharge time period is unknown. OBJECTIVE: To examine the association between time since hospital discharge and opioid overdose among individuals prescribed LTOT. DESIGN: Self-controlled risk interval analysis. PARTICIPANTS: Adults prescribed LTOT with at least one hospital discharge at a safety-net health system and a non-profit healthcare organization in Colorado. MAIN MEASURES: We identified individuals prescribed LTOT who were discharged from January 2006 through June 2019. The outcome was a composite of fatal and non-fatal opioid overdoses during a 90-day post-discharge observation period, identified using electronic health record (EHR) and vital statistics data. Risk intervals included days 0-6 after index and subsequent hospital discharges. Control intervals ranged from days 7 to 89 after index discharge and included all other time during the observation period that did not fall within a risk interval or time readmitted during a subsequent hospitalization, which was excluded. Poisson regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for overdose events during risk in comparison to control intervals. KEY RESULTS: We identified 7695 adults (63.3% over 55 years, 59.4% female, 20.3% Hispanic) who experienced 9499 total discharges during the study period. Twenty-one overdoses occurred during their observation periods (1174 per 100,000 person-years [9 in risk, 12 in control]). Overdose risk was significantly higher during the risk interval in comparison to the control interval (IRR 6.92; 95% CI 2.92-16.43). CONCLUSION: During the first 7 days after hospital discharge, individuals prescribed LTOT appear to be at elevated risk for opioid overdose. Clarifying mechanisms of overdose risk may help inform in-hospital and post-discharge prevention strategies.


Assuntos
Overdose de Drogas , Overdose de Opiáceos , Adulto , Humanos , Feminino , Masculino , Analgésicos Opioides/uso terapêutico , Overdose de Opiáceos/complicações , Overdose de Opiáceos/tratamento farmacológico , Assistência ao Convalescente , Alta do Paciente , Overdose de Drogas/prevenção & controle , Hospitais
9.
COPD ; 20(1): 64-70, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36656666

RESUMO

Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p < 0.001) and one-year mortality (70% vs. 43%; p < 0.001). Multivariable logistic and Cox regression models adjusted for age, sex and SAPS3 score confirmed higher mortality in LTOT, odds ratio for 30-day mortality was 1.8 ([95% confidence interval] 1.5-2.3) and hazard ratio for one-year mortality was 1.8 (1.6-2.0). In summary, although need for LTOT is a negative prognostic marker for survival after AECOPD requiring intensive care, a majority of patients with LTOT survived the AECOPD and 30% were alive after one year.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos de Coortes , Prognóstico , Cuidados Críticos , Oxigênio
10.
Thorax ; 77(10): 1030-1035, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35907640

RESUMO

The Winter Meeting of the British Thoracic Society (BTS) is a platform for the latest clinical and scientific research in respiratory medicine. This review summarises the key symposia and presentations from the BTS Winter Meeting 2021 held online due to the COVID-19 pandemic.


Assuntos
COVID-19 , Pneumologia , Humanos , Pandemias/prevenção & controle , COVID-19/epidemiologia , Sociedades Médicas
11.
Ann Am Thorac Soc ; 19(10): 1677-1686, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35657698

RESUMO

Rationale: Long-term oxygen therapy (LTOT) is prescribed for at least 15 hours per day and often used by patients for several years, but knowledge is limited regarding adverse effects, risk exposures, and health-related quality of life (HrQoL) among those treated. Objectives: To determine the prevalence of adverse effects, smoking, and alcohol consumption and their relations to HrQoL among patients treated with LTOT. Methods: This was a cross-sectional survey of a randomized sample of adults with ongoing LTOT in the Swedish National Registry for Respiratory Failure (Swedevox). Patient characteristics and the prevalence of 26 prespecified adverse effects, smoking, and alcohol consumption, were compared between respondents with better and worse HrQoL on the chronic obstructive pulmonary disease assessment test. Results: A total of 151 respondents were included (mean age, 74.7 yr [standard deviation, 8.6 yr]; 58.9% women; median LTOT duration, 2.2 yr [interquartile range, 1.0-3.8 yr]). Characteristics upon starting LTOT were similar between respondents and nonrespondents. Active smoking was very rare (n = 4, 2.6%). For alcohol use, 67.2% of participants reported no consumption during an average week, whereas risk use was reported by 25.8% of men and 16.9% of women. The most prevalent adverse effects were reduced mobility or physical activity (70.9%), dry mouth (69.5%), congestion or nasal drip (61.6%), increased tiredness (57.0%), and dry nose (53.0%). Patients with higher numbers of total and systemic adverse effects experienced worse HrQoL, whereas no associations were found for smoking status or alcohol consumption. The majority (54.8%) of adverse effects were untreated and unreported to health professionals. Conclusions: Adverse effects are common among patients with LTOT and are associated with worse HrQoL. As the majority of adverse effects had not been discussed or treated, structured assessment and management of risk exposures and adverse effects is warranted.


Assuntos
Consumo de Bebidas Alcoólicas , Oxigenoterapia , Qualidade de Vida , Fumar , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Oxigenoterapia/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia
12.
IDCases ; 29: e01528, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694274

RESUMO

Background: Patients having undergone B-cell-depletion with anti-CD20-antibodies have a higher risk of mortality, delayed viral clearance and prolonged infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report two cases of patients with persistent coronavirus disease 2019 (COVID-19) in association with B-cell-depletion that were treated with the monoclonal antibody Sotrovimab. Case presentation: Both patients presented with chronic symptoms of COVID-19 such as dyspnea, fatigue, and chest pain. Nasopharyngeal swabs remained positive months after the initial infection with fluctuating cycle threshold (Ct) values around 30. Both patients received a single infusion with the monoclonal SARS-CoV-2 antibody Sotrovimab, which resulted in a rapid improvement of symptoms and inflammation markers as well as negative SARS-CoV-2 swabs. A follow-up after a month showed ongoing improvement of symptoms, persistent negative SARS-CoV-2 swabs, and positive serum antibodies. Conclusion: Infusion with the monoclonal SARS-CoV-2 antibody led to rapid improvement in two patients with persistent COVID-19 after B-cell depletion.

13.
Int J Chron Obstruct Pulmon Dis ; 17: 1311-1322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686212

RESUMO

Purpose: To estimate the 5-year budget impact to Aotearoa New Zealand (NZ) hospitals of domiciliary nasal high flow (NHF) therapy to patients with chronic obstructive pulmonary disease (COPD) who require long term oxygen therapy. Methods: Hospital admission counts along with length of stay were obtained from hospital records of 200 COPD patients enrolled in a 12-month randomized clinical trial of NHF in Denmark, both over a 12-month baseline and then in the study period while on randomized treatment (control or NHF). NZ costings from similar COPD patients were estimated using data from Middlemore Hospital, Auckland and were applied to the Danish trial. The budget impact of NHF was estimated over the predicted 5-year lifetime of the device when used by patients sequentially. Results: Fifty-five of 100 patients in the NHF group and 44 of 100 patients in the control group were admitted to hospital with a respiratory diagnosis during the baseline year. They had 108 admissions in the treatment group vs 89 in the control group, with 632 vs 438 days in hospital, and modeled annual costs of $9443 vs $6512 per patient, respectively. During the study period there were 38 vs 44 patients with 67 vs 80 admissions and 302 vs 526 days in hospital, at a modeled annual cost of $6961 vs $9565 per patient respectively. Taking into account capital expenditure and running costs, this resulted in cost savings of $5535 per patient-year (95% CI, -$36 to -$11,034). With 90% usage over the estimated five-year lifetime of the NHF device, amortized capital costs of $594 per year and annual running costs of $662, we estimate a 5-year undiscounted cost saving per NHF device of $18,626 ($16,934 when discounted to net present value at 5% per annum). There would still be annual cost savings over a wide range of assumptions. Conclusion: Domiciliary NHF therapy for patients with severe COPD has the potential to provide substantial hospital cost savings over the five-year lifetime of the NHF device.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Redução de Custos , Custos Hospitalares , Hospitais , Humanos , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia
14.
Arch Bronconeumol ; 58(9): 642-648, 2022 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35312537

RESUMO

BACKGROUND: Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear. AIM: To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution. STUDY DESIGN AND METHODS: This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020. RESULTS: A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3). INTERPRETATION: A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival.


Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Síndromes da Apneia do Sono , Análise por Conglomerados , Feminino , Humanos , Masculino , Obesidade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial
15.
Respir Investig ; 60(1): 137-145, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34583896

RESUMO

BACKGROUND: Some chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO2, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown. METHODS: We retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n = 76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n = 130). RESULTS: In the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p = 0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p = 0.006), lower %DLCO/VA (HR, 0.90, p = 0.008), higher RV/TLC (HR, 1.26, p = 0.012), higher LAA% (HR: 1.18, p = 0.001), and lower fractal D (HR: 3.27 × 10-8, p < 0.001) were associated with LTOT initiation. Multivariate analysis in the Kyoto University cohort confirmed that lower %DLCO and lower fractal D were independently associated with LTOT initiation, whereas LAA% was not. CONCLUSION: Fractal D, which is the index for morphometric complexity of LAA in CT analysis, is predictive of LTOT initiation in COPD patients.


Assuntos
Fractais , Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Humanos , Oxigênio , Oxigenoterapia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
Thorax ; 77(1): 47-57, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33883249

RESUMO

INTRODUCTION: Neonatal lung injury as a consequence of hyperoxia (HO) therapy and ventilator care contribute to the development of bronchopulmonary dysplasia (BPD). Increased expression and activity of lysyl oxidase (LOX), a key enzyme that cross-links collagen, was associated with increased sphingosine kinase 1 (SPHK1) in human BPD. We, therefore, examined closely the link between LOX and SPHK1 in BPD. METHOD: The enzyme expression of SPHK1 and LOX were assessed in lung tissues of human BPD using immunohistochemistry and quantified (Halo). In vivo studies were based on Sphk1-/- and matched wild type (WT) neonatal mice exposed to HO while treated with PF543, an inhibitor of SPHK1. In vitro mechanistic studies used human lung microvascular endothelial cells (HLMVECs). RESULTS: Both SPHK1 and LOX expressions were increased in lungs of patients with BPD. Tracheal aspirates from patients with BPD had increased LOX, correlating with sphingosine-1-phosphate (S1P) levels. HO-induced increase of LOX in lungs were attenuated in both Sphk1-/- and PF543-treated WT mice, accompanied by reduced collagen staining (sirius red). PF543 reduced LOX activity in both bronchoalveolar lavage fluid and supernatant of HLMVECs following HO. In silico analysis revealed STAT3 as a potential transcriptional regulator of LOX. In HLMVECs, following HO, ChIP assay confirmed increased STAT3 binding to LOX promoter. SPHK1 inhibition reduced phosphorylation of STAT3. Antibody to S1P and siRNA against SPNS2, S1P receptor 1 (S1P1) and STAT3 reduced LOX expression. CONCLUSION: HO-induced SPHK1/S1P signalling axis plays a critical role in transcriptional regulation of LOX expression via SPNS2, S1P1 and STAT3 in lung endothelium.


Assuntos
Hiperóxia , Lesão Pulmonar , Animais , Células Endoteliais , Humanos , Camundongos , Fosfotransferases (Aceptor do Grupo Álcool) , Proteína-Lisina 6-Oxidase , Fator de Transcrição STAT3
17.
Thorax ; 77(10): 968-975, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34853156

RESUMO

RATIONALE: Dietary nitrate supplementation improves skeletal muscle oxygen utilisation and vascular endothelial function. We hypothesised that these effects might be sufficient to improve exercise performance in patients with COPD and hypoxia severe enough to require supplemental oxygen. METHODS: We conducted a single-centre, double-blind, placebo-controlled, cross-over study, enrolling adults with COPD who were established users of long-term oxygen therapy. Participants performed an endurance shuttle walk test, using their prescribed oxygen, 3 hours after consuming either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate) or placebo (nitrate-depleted BRJ). Treatment order was allocated (1:1) by computer-generated block randomisation. MEASUREMENTS: The primary outcome was endurance shuttle walk test time. The secondary outcomes included area under the curve to isotime for fingertip oxygen saturation and heart rate parameters during the test, blood pressure, and endothelial function assessed using flow-mediated dilatation. Plasma nitrate and nitrite levels as well as FENO were also measured. MAIN RESULTS: 20 participants were recruited and all completed the study. Nitrate-rich BRJ supplementation prolonged exercise endurance time in all participants as compared with placebo: median (IQR) 194.6 (147.5-411.7) s vs 159.1 (121.9-298.5) s, estimated treatment effect 62 (33-106) s (p<0.0001). Supplementation also improved endothelial function: NR-BRJ group +4.1% (-1.1% to 14.8%) vs placebo BRJ group -5.0% (-10.6% to -0.6%) (p=0.0003). CONCLUSION: Acute dietary nitrate supplementation increases exercise endurance in patients with COPD who require supplemental oxygen. Trial registration number ISRCTN14888729.


Assuntos
Nitratos , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estudos Cross-Over , Tolerância ao Exercício , Suplementos Nutricionais , Antioxidantes , Oxigênio , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Hipóxia , Método Duplo-Cego
18.
Eur Spine J ; 30(10): 2989-2998, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33893870

RESUMO

PURPOSE: No reference material exists on the scope of long-term problems in novel spinal pain opioid users. In this study, we evaluate the prevalence and long-term use of prescribed opioids in patients of the Spinal Pain Opioid Cohort. METHODS: The setting was an outpatient healthcare entity (Spine Center). Prospective variables include demographics, clinical data collected in SpineData, and The Danish National Prescription Registry. Patients with a new spinal pain episode lasting for more than two months, aged between 18 and 65 years, who had their first outpatient visit. Based on the prescription of opioids from 4 years before the first spine center visit to 5 years after, six or more opioid prescriptions in a single 1-year interval fulfilled the main outcome criteria Long-Term Opioid Therapy (LTOT). RESULTS: Overall, of 8356 patients included in the cohort, 4409 (53%) had one or more opioid prescriptions in the registered nine years period. Of opioid users, 2261 (27%) were NaiveStarters receiving their first opioid prescription after a new acute pain episode; 2148(26%) PreStarters had previously received opioids. The prevalence of LTOT in PreStarters/NaiveStarters was 17.2%/11.2% in their first outpatient year. Similar differences between groups were seen in all follow-up intervals. In the last follow-up year, LTOT prevalence in Prestarters/NaiveStarters was 12.5%/7.0%. CONCLUSIONS: Previous opioid treatment-i.e., before a new acute spinal pain episode and referral to a Spine Center-doubled the risk of LTOT 5 years later. The results underscore clinicians' obligation to carefully and individually weigh the benefits against the risks of prescribing opioid therapy. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.


Assuntos
Dor Aguda , Analgésicos Opioides , Adolescente , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prevalência , Estudos Prospectivos , Adulto Jovem
19.
Thorax ; 76(12): 1200-1208, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33927018

RESUMO

BACKGROUND: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD. METHODS: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible. RESULTS: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy. CONCLUSION: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.


Assuntos
Doenças Pulmonares Intersticiais , Apneia Obstrutiva do Sono , Humanos , Hipóxia/etiologia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/epidemiologia , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia
20.
Thorax ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653932

RESUMO

An application (app) for the Severe Respiratory Insufficiency Questionnaire (SRI) has been designed and developed for mobile devices. In a randomised controlled trial comprising 60 patients with chronic respiratory failure, the app was compared with the classic paper SRI. Thereby, it was shown that the SRI app is a practical tool that is well accepted. Missing values can be completely avoided by using the SRI app. Finally, reliability, convergent and discriminant validities were established. Accordingly, for the individual SRI subscales, Cronbach's alpha ranged between 0.56 and 0.81 (app) and between 0.54 and 0.83 (paper), respectively. The multilingual SRI app is accessible free of charge for non-profit research purposes.

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