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1.
Respirology ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33876511

RESUMO

BACKGROUND AND OBJECTIVE: Physical frailty is associated with increased mortality and hospitalizations in older adults. We describe the prevalence of physical frailty and its prognostic impact in patients with a spectrum of fibrotic interstitial lung disease (ILD). METHODS: Patients with fibrotic ILD at the McMaster University ILD programme were prospectively followed up from November 2015 to March 2020. Baseline data were used to classify patients as non-frail (score = 0), pre-frail (score = 1-2) or frail (score = 3-5) based on modified Fried physical frailty criteria. The association between physical frailty and mortality was assessed using time-to-event models, adjusted for age, sex, lung function and diagnosis using the ILD Gender-Age-Physiology (ILD-GAP) score. RESULTS: We included 463 patients (55% male, mean [SD] age 68 [11] years); 82 (18%) were non-frail, 258 (56%) pre-frail and 123 (26%) frail. The most common ILD diagnoses were idiopathic pulmonary fibrosis (n = 183, 40%) and connective tissue disease-associated-ILD (n = 79, 17%). Mean time since diagnosis was 2.7 ± 4.6 years. There were 56 deaths within the median follow-up of 1.71 (interquartile range [IQR] 1.24, 2.31) years. Both frail and pre-frail individuals had a higher risk of death compared to those categorized as non-frail at baseline (adjusted hazard ratio [aHR] 4.14, 95% CI 1.27-13.5 for pre-frail and aHR 4.41, 95% CI 1.29-15.1 for frail). CONCLUSION: Physical frailty is prevalent in patients with ILD and is independently associated with an increased risk of death. Assessment of physical frailty provides additional prognostic value to recognized risk scores such as the ILD-GAP score, and may present a modifiable target for intervention.

2.
EBioMedicine ; 66: 103325, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33862585

RESUMO

BACKGROUND: The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition. METHODS: Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples. FINDINGS: The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis. INTERPRETATION: The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis.

3.
Thorax ; 2021 Apr 29.
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.

5.
Chest ; 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33905679

RESUMO

BACKGROUND: Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD is currently unknown. RESEARCH QUESTION: What are the epidemiology of hypoxemia and its additive prognostic value in current risk prediction model in fibrotic ILD? METHODS: We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis (IPF)) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-minute walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality/transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the "ILD-GAP-O2" model), which included oxygenation status as a predictor. RESULTS: The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1% for exertional hypoxemia, and 2.4%, 5.6%, and 16.5% for resting hypoxemia, which were significantly higher in IPF patients compared to non-IPF patients (p<0.001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality/transplantation prediction (p<0.001 for both). The ILD-GAP-O2 model had improved discrimination (C-index of 0.80 vs 0.75) and model fit (Akaike information criteria of 400 vs 422) in the validation cohort, with comparable calibration. INTERPRETATION: IPF patients have higher cumulative incidence of exertional and resting hypoxemia than non-IPF patients. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.

6.
Respir Physiol Neurobiol ; 288: 103644, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33647535

RESUMO

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV1 (p = 0.04), DLCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower DLCO, reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19.


Assuntos
/complicações , Dispneia/fisiopatologia , Tolerância ao Exercício , Fadiga/fisiopatologia , Troca Gasosa Pulmonar , Espirometria , Adulto , Idoso , Doença Crônica , Dispneia/sangue , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Testes de Função Respiratória , Índice de Gravidade de Doença , Sobreviventes , Capacidade Vital , Teste de Caminhada
7.
Sci Rep ; 11(1): 6874, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767311

RESUMO

Dyspnoea is a cardinal symptom of fibrotic interstitial lung disease (ILD), with a lack of proven effective therapies. With emerging evidence of the role of facial and nasal airflow for relieving breathlessness, this pilot study was conducted to examine the feasibility of conducting a clinical trial of a handheld fan (HHF) for dyspnoea management in patients with fibrotic ILD. In this mixed-methods, randomised, assessor-blinded, controlled trial, 30 participants with fibrotic ILD who were dyspnoeic with a modified Medical Research Council Dyspnoea grade ≥ 2 were randomised to a HHF for symptom control or no intervention for 2 weeks. Primary outcomes were trial feasibility, change in Dyspnoea-12 scores at Week 2, and participants' perspectives on using a HHF for dyspnoea management. Study recruitment was completed within nine months at a single site. Successful assessor blinding was achieved in the fan group [Bang's Blinding Index - 0.08 (95% CI - 0.45, 0.30)] but not the control group [0.47 (0.12, 0.81)]. There were no significant between-group differences for the change in Dyspnoea-12 or secondary efficacy outcomes. During qualitative interviews, participants reported that using the HHF relieved breathlessness and provided relaxation, despite initial scepticism about its therapeutic benefit. Oxygen-experienced participants described the HHF being easier to use, but not as effective for symptomatic relief, compared to oxygen therapy. Our results confirmed the feasibility of a clinical trial of a HHF in fibrotic ILD. There was a high level of patient acceptance of a HHF for managing dyspnoea, with patients reporting both symptomatic benefits and ease of use.

8.
Sleep Med Rev ; 58: 101442, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33561604

RESUMO

Obstructive sleep apnea (OSA) is one of the most common comorbidities in patients with interstitial lung disease (ILD). Growing evidence highlights the significance of sleep disturbance on health outcomes in this population. The relationships between ILD and OSA are complex and possibly bidirectional, with multiple mechanisms postulated for the pathogenic and physiologic links. This review synthesizes current evidence and hypotheses regarding different aspects of the relationships between ILD and OSA, emphasizing the interactions between epidemiology, pathogenesis, and pathophysiology.

12.
Eur Respir J ; 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574070

RESUMO

INTRODUCTION: for the management of patients referred to respiratory triage during the early stages of the SARS-CoV-2 pandemic, either chest radiograph (CXR) or computed tomography (CT) were used as first-line diagnostic tools. The aim of this study was to compare the impact on triage, diagnosis and prognosis of patients with suspected COVID-19 when clinical decisions are derived from reconstructed CXR or from CT. METHODS: we reconstructed CXR (r-CXR) from high-resolution CT (HRCT) scan. Five clinical observers independently reviewed clinical charts of 300 subjects with suspected COVID-19 pneumonia, integrated with either r-CXR or HRCT report in two consecutive blinded and randomised sessions: clinical decisions were recorded for each session. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and prognostic value were compared between r-CXR and HRCT. The best radiological integration was also examined to develop an optimised respiratory triage algorithm. RESULTS: interobserver agreement was fair (Kendall's W=0.365; p<0.001) by r-CXR-based protocol and good (Kendall's W=0.654; p<0.001) by CT-based protocol. NPV assisted by r-CXR (31.4%) was lower than that of HRCT (77.9%). In case of indeterminate or typical radiological appearence for COVID-19 pneumonia, extent of disease on r-CXR or HRCT were the only two imaging variables that were similarly linked to mortality by adjusted multivariable models CONCLUSIONS: the present findings suggest that clinical triage is safely assisted by CXR. An integrated algorithm using first-line CXR and contingent use of HRCT can help optimise management and prognostication of COVID-19.

13.
Chest ; 159(3): 1107-1125, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33450293

RESUMO

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others.

15.
Radiology ; 298(3): 531-549, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33399507

RESUMO

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

16.
Eur Respir J ; 57(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33402372

RESUMO

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: a) Is noninvasive imaging capable of identifying PH? b) What is the role of imaging in establishing the cause of PH? c) How does imaging determine the severity and complications of PH? d) How should imaging be used to assess chronic thromboembolic PH before treatment? e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH.

17.
Radiology ; 298(3): 550-566, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33434111

RESUMO

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in Radiology and CHEST. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

18.
Ann Am Thorac Soc ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33493425

RESUMO

RATIONALE: Real-life pharmacological treatment patterns of patients with interstitial lung diseases (ILD) remain elusive. OBJECTIVES: The objective of this study was to determine how often and with what medications patients with ILD are treated in Canadian tertiary care clinics. METHODS: All patients with ILD prospectively enrolled in the Canadian Registry for Pulmonary Fibrosis were included in this observational study. All first instances of medication for each patient were compiled. Time between the diagnosis of ILD and the first initiation of an ILD-related medication was compared across diagnostic categories. Cox proportional hazards models were used to identify variables associated with time-to-treatment initiation, stratified by diagnostic category. RESULTS: Out of 2,652 patients, a total of 1,483 (56%) were treated with an ILD-related medication during the median follow-up of 3.0 years (1.4 to 5.9), including 349/646 (54%) patients with idiopathic pulmonary fibrosis (IPF) who received an antifibrotic. Patients with IPF were treated earlier and in greater proportion compared to those with non-IPF ILD (p=0.001). Male sex and lower lung function were associated with shorter time to treatment initiation in the full cohort. CONCLUSIONS: Overall, 56% of patients with ILD seen across seven Canadian specialized ILD clinics received pharmacological treatment over a median follow-up of 3 years. Further studies are needed to assess longitudinal patterns of treatment and their influence on key outcomes.

19.
Respir Res ; 21(1): 322, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287805

RESUMO

BACKGROUND: Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality. METHODS: Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters. RESULTS: Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (- 11.9% per year [95% CI - 15.3, - 8.5]) compared to females without any comorbidities (- 8.1% per year [95% CI - 13.6, - 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes. CONCLUSIONS: The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

20.
Thorax ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273023

RESUMO

The long-term respiratory morbidity of COVID-19 remains unclear. We describe the clinical, radiological and pulmonary function abnormalities that persist in previously hospitalised patients assessed 12 weeks after COVID-19 symptom onset, and identify clinical predictors of respiratory outcomes. At least one pulmonary function variable was abnormal in 58% of patients and 88% had abnormal imaging on chest CT. There was strong association between days on oxygen supplementation during the acute phase of COVID-19 and both DLCO-% (diffusion capacity of the lung for carbon monoxide) predicted and total CT score. These findings highlight the need to develop treatment strategies and the importance of long-term respiratory follow-up after hospitalisation for COVID-19.

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