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1.
Am J Case Rep ; 21: e926921, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219200

RESUMO

BACKGROUND Since December 2019, an outbreak caused by a novel coronavirus infection (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) occurred in Wuhan, China, and it rapidly spread all over the world. The clinical spectrum of coronavirus disease 2019 (COVID-19) is wide, with acute respiratory distress syndrome (ARDS) occurring in 15% of patients affected, requiring high oxygen support. Currently, there is no clearly effective antiviral therapy. Steroids and immunomodulators are under investigation for potential activity. Little is known about middle and long-term sequelae on respiratory function. According to some authors, COVID-19 could cause pulmonary fibrosis. We report 3 cases of pulmonary fibrosis detected on follow-up computed tomography (CT) imaging in 3 female patients who recovered from COVID-19 pneumonia in Italy (L'Aquila, Abruzzo). CASE REPORT All patients were female and had no significant previous respiratory disease or history of smoke exposure, and none had received high-flow oxygen support during treatment of the disease. In all cases, late onset of mild dyspnea, slow and incomplete respiratory recovery, and early evidence of fibrous signs on chest CT scan were characteristic of the clinical course. CONCLUSIONS This report focuses on a possible scenario of long-term lung damage in COVID-19 pneumonia survivors. Limitations are lack of long-term follow-up and functional data in the very early phase. It is advantageous that all COVID-19 pneumonia patients undergo serial chest CT and spirometry long-term follow-up for at least 1 year to assess residual damage. This is particularly relevant in those with slow respiratory recovery and long hospitalization.


Assuntos
/diagnóstico , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , /epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pandemias , Fibrose Pulmonar/complicações , Radiografia Torácica
3.
PLoS One ; 15(9): e0239066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941486

RESUMO

BACKGROUND: Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial fibrosis. However, ambiguous diagnostic criteria and, particularly, the absence of objective methods to quantify emphysematous/fibrotic lesions in patients with CPFE confound the interpretation of the pathophysiology of this syndrome. We analyzed the relationship between objectively quantified computed tomography (CT) measurements and the results of pulmonary function testing (PFT) and clinical events in CPFE patients. MATERIALS AND METHODS: We enrolled 46 CPFE patients who underwent CT and PFT. The extent of emphysematous lesions was obtained by calculating the percent of low attenuation area (%LAA). The extent of fibrotic lesions was calculated as the percent of high attenuation area (%HAA). %LAA and %HAA values were combined to yield the percent of abnormal area (%AA). We assessed the relationships between CT parameters and other clinical indices, including PFT results. Multivariate analysis was performed to examine the association between the CT parameters and clinical events. RESULTS: A greater negative correlation with percent predicted diffusing capacity of the lung for carbon monoxide (DLCO %predicted) existed for %AA (r = -0.73, p < 0.001) than for %LAA or %HAA alone. The %HAA value was inversely correlated with percent predicted forced vital capacity (r = -0.48, p < 0.001), percent predicted total lung capacity (r = -0.48, p < 0.01), and DLCO %predicted (r = -0.47, p < 0.01). Multivariate logistic regression analysis found that %AA showed the strongest association with hospitalization events (odds ratio = 1.20, 95% confidence interval = 1.01-1.54, p = 0.029). CONCLUSION: Quantitative CT measurements reflected deterioration in pulmonary function and were associated with hospitalization in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and the clinical course of patients with CPFE.


Assuntos
Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Feminino , Humanos , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Enfisema Pulmonar/complicações , Enfisema Pulmonar/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Testes de Função Respiratória
4.
J Proteome Res ; 19(11): 4327-4338, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32883081

RESUMO

The COVID-19 pandemic rapidly became a worldwide healthcare emergency affecting millions of people, with poor outcomes for patients with chronic conditions and enormous pressure on healthcare systems. Pulmonary fibrosis (PF) has been cited as a risk factor for a more severe evolution of COVID-19, primarily because its acute exacerbations are already associated with high mortality. We reviewed the available literature on biochemical, pathophysiological, and pharmacological mechanisms of PF and COVID-19 in an attempt to foresee the particular risk of infection and possible evolution of PF patients if infected with SARS-COV-2. We also analyzed the possible role of medication and risk factors (such as smoking) in the disease's evolution and clinical course. We found out that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/interstitial lung disease (ILD) and COVID-19 disease. Also, patients recovering from severe COVID-19 disease are at serious risk of developing PF. Smokers seem to have, in theory, a chance for a better outcome if they develop a severe form of COVID-19 but statistically are at much higher risk of dying if they become critically ill.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Fibrose Pulmonar , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/fisiopatologia , Fatores de Risco , Fumar
5.
Pulm Med ; 2020: 6175964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850151

RESUMO

Although pulmonary fibrosis can occur in the absence of a clear-cut inciting agent, and without a clinically clear initial acute inflammatory phase, it is more commonly associated with severe lung injury. This may be due to respiratory infections, chronic granulomatous diseases, medications, and connective tissue disorders. Pulmonary fibrosis is associated with permanent pulmonary architectural distortion and irreversible lung dysfunction. Available clinical, radiographic, and autopsy data has indicated that pulmonary fibrosis is central to severe acute respiratory distress syndrome (SARS) and MERS pathology, and current evidence suggests that pulmonary fibrosis could also complicate infection by SARS-CoV-2. The aim of this review is to explore the current literature on the pathogenesis of lung injury in COVID-19 infection. We evaluate the evidence in support of the putative risk factors for the development of lung fibrosis in the disease and propose risk mitigation strategies. We conclude that, from the available literature, the predictors of pulmonary fibrosis in COVID-19 infection are advanced age, illness severity, length of ICU stay and mechanical ventilation, smoking and chronic alcoholism. With no proven effective targeted therapy against pulmonary fibrosis, risk reduction measures should be directed at limiting the severity of the disease and protecting the lungs from other incidental injuries.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Fibrose Pulmonar/complicações , Comportamento de Redução do Risco , Sobreviventes/estatística & dados numéricos , Fatores Etários , Alcoolismo/complicações , Humanos , Tempo de Internação/estatística & dados numéricos , Pandemias , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Tabagismo/complicações
6.
Chest ; 158(6): 2270-2274, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32693101
7.
Rev Mal Respir ; 37(7): 561-571, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32684338

RESUMO

INTRODUCTION: Common major pathogens like Pseudomonas aeruginosa are identified in the airways of patients with cystic fibrosis (CF) and non-CF bronchiectasis. However, other opportunistic bacterial pathogens like Achromobacter xylosoxidans complex, Stenotrophomonas maltophilia and non-tuberculous mycobacteria are currently emerging in CF and are also reported in non-CF bronchiectasis. BACKGROUND: The emergence of opportunistic bacterial pathogens has been recognized in CF through annual national reports of sputum microbiology data. Despite common factors driving the emergence of bacteria identified in CF and non-CF bronchiectasis patients, bronchiectasis registries have been created more recently and no longitudinal analysis of recorded microbiological data is currently available in the literature, thereby preventing the recognition of emerging bacteria in patients with non-CF bronchiectasis. OUTLOOK: A longitudinal follow-up of microbiological data is still needed in non-CF bronchiectasis to identify emerging opportunistic bacterial pathogens. Homogeneity in practice of sputum microbiological examination is also required to allow comparative analysis of data in CF and non-CF bronchiectasis. CONCLUSION: Bacterial pathogens recognized as emerging in CF have to be more carefully monitored in non-CF bronchiectasis in view of their association with deterioration of the lung disease.


Assuntos
Bronquiectasia/microbiologia , Fibrose Cística/microbiologia , Microbiologia/tendências , Fibrose Pulmonar/microbiologia , Infecções Respiratórias/microbiologia , Bronquiectasia/complicações , Bronquiectasia/epidemiologia , Bronquiectasia/terapia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Doenças Transmissíveis Emergentes/terapia , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Humanos , Técnicas Microbiológicas/estatística & dados numéricos , Técnicas Microbiológicas/tendências , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Monitorização Fisiológica/tendências , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/terapia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/terapia , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/terapia , Escarro/microbiologia
8.
J Xray Sci Technol ; 28(3): 383-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474479

RESUMO

PURPOSE: To analyze clinical and thin-section computed tomographic (CT) data from the patients with coronavirus disease (COVID-19) to predict the development of pulmonary fibrosis after hospital discharge. MATERIALS AND METHODS: Fifty-nine patients (31 males and 28 females ranging from 25 to 70 years old) with confirmed COVID-19 infection performed follow-up thin-section thorax CT. After 31.5±7.9 days (range, 24 to 39 days) of hospital admission, the results of CT were analyzed for parenchymal abnormality (ground-glass opacification, interstitial thickening, and consolidation) and evidence of fibrosis (parenchymal band, traction bronchiectasis, and irregular interfaces). Patients were analyzed based on the evidence of fibrosis and divided into two groups namely, groups A and B (with and without CT evidence of fibrosis), respectively. Patient demographics, length of stay (LOS), rate of intensive care unit (ICU) admission, peak C-reactive protein level, and CT score were compared between the two groups. RESULTS: Among the 59 patients, 89.8% (53/59) had a typical transition from early phase to advanced phase and advanced phase to dissipating phase. Also, 39% (23/59) patients developed fibrosis (group A), whereas 61% (36/59) patients did not show definite fibrosis (group B). Patients in group A were older (mean age, 45.4±16.9 vs. 33.8±10.2 years) (P = 0.001), with longer LOS (19.1±5.2 vs. 15.0±2.5 days) (P = 0.001), higher rate of ICU admission (21.7% (5/23) vs. 5.6% (2/36)) (P = 0.061), higher peak C-reactive protein level (30.7±26.4 vs. 18.1±17.9 mg/L) (P = 0.041), and higher maximal CT score (5.2±4.3 vs. 4.0±2.2) (P = 0.06) than those in group B. CONCLUSIONS: Pulmonary fibrosis may develop early in patients with COVID-19 after hospital discharge. Older patients with severe illness during treatment were more prone to develop fibrosis according to thin-section CT results.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pulmão/diagnóstico por imagem , Alta do Paciente , Pneumonia Viral/complicações , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos
9.
Respir Med ; 169: 105997, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32442108

RESUMO

INTRODUCTION: Pulmonary fibrosing sarcoidosis is associated with increased mortality. This study was aimed to explore the prognosis value of a panel of parameters for predicting mortality. METHODS: This retrospective study included 216 patients with confirmed stage 4 pulmonary sarcoidosis. Stage 4 diagnosis date served as baseline. The following information was systematically present at baseline: epidemiological characteristics; treatments; pulmonary function; composite physiologic index (CPI); systolic pulmonary artery pressure at echocardiography; pulmonary fibrosis extent, main pulmonary artery/ascending aorta diameters ratio (MPAD/AAD) and MPAD/body surface area (BSA) measured and calculated using computed tomography, Walsh's algorithm based on CPI, lung fibrosis extent and MPAD/AAD ratio, and modified Walsh's algorithm with MPAD/BSA replacing MPAD/AAD allowed to estimate good or bad prognosis profiles. The primary outcome of the study was all cause mortality and lung transplantation. The value of baseline parameters was tested as predictors of mortality using univariate and multivariate analyses. RESULTS: Median follow-up was 105 months. There were 41 deaths and 5 transplantations. At multivariate analysis, survival was independently predicted by several parameters including CPI, lung fibrosis extent, pulmonary hypertension at echography or MPAD/BSA ratio, Walsh's algorithm, and geographic origin. The modified Walsh's algorithm was most highly predictive. CONCLUSION: Survival was best predicted by geographic origin, lung fibrosis extent, PH at echography or MPAD/BSA ratio, as well as by various scores among them the modified Walsh's algorithm had very high predictive value thanks to MPAD/BSA ratio which accurately predicted mortality.


Assuntos
Algoritmos , Fibrose Pulmonar/mortalidade , Sarcoidose Pulmonar/mortalidade , Aorta/patologia , Superfície Corporal , Seguimentos , Hipertensão Pulmonar , Valor Preditivo dos Testes , Prognóstico , Artéria Pulmonar/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
11.
Transplant Proc ; 52(7): 2101-2109, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336653

RESUMO

INTRODUCTION: Secondary pulmonary hypertension (PH) is a serious complication of end-stage lung disease and is associated with unfavorable prognosis. The aim of the study was to evaluate the incidence and severity of secondary PH among patients qualified for lung transplantation (LTx). MATERIAL AND METHODS: The study population consisted of 143 patients qualified for LTx between 2004 and 2019. Analyzed medical records included results collected during the qualification process (eg, echocardiography parameters, right heart catherization [RHC]). There were 37.8% (n = 54) of patients with chronic obstructive pulmonary disease (COPD), 58.7% (n = 84) of patients with interstitial lung diseases (ILDs), and 3.5% (n = 5) of patients with combined pulmonary fibrosis and emphysema (CPFE). The inclusion criteria were ILDs, COPD or CPFE diagnosis, and the presence of RHC data preformed during qualification for LTx. The exclusion criteria were lack of RHC results and diagnosis of idiopathic pulmonary artery hypertension, pulmonary artery hypertension associated with connective tissue disease, cystic fibrosis, or bronchiectasis. RESULTS: PH was detected among 60.1% (n = 86) of patients qualified for LTx. The prevalence of PH was 39% (n = 18) vs 76.19% (n = 64) in the COPD vs ILDs groups, respectively. Both ILDs and COPD patients presented with similar mean artery pulmonary pressure (36.3 ± 9.61 vs 34.78 ± 11.47 mm Hg; not statistically significant). Severe PH was more frequent in the ILDs group than in the COPD group (60.94% vs 38.89%). CONCLUSIONS: PH is commonly diagnosed in patients with chronic lung diseases qualified for LTx and more often observed among patients qualified because of ILDs. It is important to assess the pulmonary pressure because of frequent occurrence of PH among patients referred for LTx.


Assuntos
Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Transplante de Pulmão , Adulto , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/cirurgia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/cirurgia , Recidiva , Estudos Retrospectivos
12.
Sci Rep ; 10(1): 4466, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161282

RESUMO

Intraflagellar transport protein 88 (Ift88) is required for ciliogenesis and shear stress-induced dissolution of cilia in embryonic endothelial cells coincides with endothelial-to-mesenchymal transition (EndMT) in the developing heart. EndMT is also suggested to underlie heart and lung fibrosis, however, the mechanism linking endothelial Ift88, its effect on EndMT and organ fibrosis remains mainly unexplored. We silenced Ift88 in endothelial cells (ECs) in vitro and generated endothelial cell-specific Ift88-knockout mice (Ift88endo) in vivo to evaluate EndMT and its contribution towards organ fibrosis, respectively. Ift88-silencing in ECs led to mesenchymal cells-like changes in endothelial cells. The expression level of the endothelial markers (CD31, Tie-2 and VE-cadherin) were significantly reduced with a concomitant increase in the expression level of mesenchymal markers (αSMA, N-Cadherin and FSP-1) in Ift88-silenced ECs. Increased EndMT was associated with increased expression of profibrotic Collagen I expression and increased proliferation in Ift88-silenced ECs. Loss of Ift88 in ECs was further associated with increased expression of Sonic Hedgehog signaling effectors. In vivo, endothelial cells isolated from the heart and lung of Ift88endo mice demonstrated loss of Ift88 expression in the endothelium. The Ift88endo mice were born in expected Mendelian ratios without any adverse cardiac phenotypes at baseline. Cardiac and pulmonary endothelial cells isolated from the Ift88endo mice demonstrated signs of EndMT and bleomycin treatment exacerbated pulmonary fibrosis in Ift88endo mice. Pressure overload stress in the form of aortic banding did not reveal a significant difference in cardiac fibrosis between Ift88endo mice and control mice. Our findings demonstrate a novel association between endothelial cilia with EndMT and cell proliferation and also show that loss of endothelial cilia-associated increase in EndMT contributes specifically towards pulmonary fibrosis.


Assuntos
Bleomicina/efeitos adversos , Transição Epitelial-Mesenquimal/genética , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Proteínas Supressoras de Tumor/deficiência , Animais , Biópsia , Movimento Celular , Proliferação de Células , Suscetibilidade a Doenças , Técnicas de Inativação de Genes , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Fibrose Pulmonar/complicações , Fibrose Pulmonar/metabolismo , Doença Cardiopulmonar/etiologia , Doença Cardiopulmonar/metabolismo , Doença Cardiopulmonar/patologia , Mucosa Respiratória/ultraestrutura , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt
13.
BMC Pulm Med ; 20(1): 51, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093665

RESUMO

BACKGROUND: Patients with fibrotic interstitial lung disease (FILD) often experience gas exchange abnormalities and ventilatory limitations, resulting in reduced exercise capacity. High-flow nasal cannula (HFNC) oxygen therapy is a novel treatment, whose physiological beneficial effects have been demonstrated in various clinical settings. We hypothesized that HFNC oxygen therapy might be superior to conventional oxygen therapy for improving exercise capacity in FILD patients. METHODS: We performed a prospective randomized controlled crossover trial with a high-intensity constant work-rate endurance test (CWRET) using HFNC (50 L/min, FiO2 0.5) and a venturi mask (VM) (15 L/min, FiO2 0.5) for oxygen delivery in FILD patients. The primary outcome variable was endurance time. The secondary outcome variables were SpO2, heart rate, Borg scale (dyspnea and leg fatigue), and patient's comfort. RESULTS: Seven hundred and eleven patients were screened and 20 eligible patients were randomized. All patients completed the trial. The majority of patients were good responders to VM and HFNC compared with the baseline test (VM 75%; HFNC 65%). There was no significant difference in endurance time between HFNC and VM (HFNC 6.8 [95% CI 4.3-9.3] min vs VM 7.6 [95% CI 5.0-10.1] min, p = 0.669). No significant differences were found in other secondary endpoints. Subgroup analysis with HFNC good responders revealed that HFNC significantly extended the endurance time compared with VM (VM 6.4 [95%CI 4.5-8.3] min vs HFNC 7.8 [95%CI 5.8-9.7] min, p = 0.046), while no similar effect was observed in the VM good responders. CONCLUSIONS: HFNC did not exceed the efficacy of VM on exercise capacity in FILD, but it may be beneficial if the settings match. Further large studies are needed to confirm these findings. TRIAL REGISTRATION: UMIN-CTR: UMIN000021901.


Assuntos
Tolerância ao Exercício , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Oxigenoterapia/métodos , Fibrose Pulmonar/fisiopatologia , Fibrose Pulmonar/terapia , Idoso , Idoso de 80 Anos ou mais , Cânula , Estudos Cross-Over , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Fibrose Pulmonar/complicações
14.
Ann Thorac Surg ; 109(6): 1677-1683, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32105715

RESUMO

BACKGROUND: Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or perioperative revascularization on lung transplant survival outcomes is not adequately established. METHODS: We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012 to 2018 (n = 468). Patients were split into 4 groups: (1) patients who received a preoperative percutaneous coronary intervention (n = 34), (2) those who received coronary artery bypass grafting (CABG) before transplantation (n = 25), (3) those that received concomitant CABG during transplantation (n = 29), and (4) those who had lung transplantation with no need for revascularization (n = 380). Groups were compared for demographics, surgical procedure, and survival outcomes. RESULTS: The no-revascularization group was statistically younger than the rest (P = .001). The lung allocation score trended toward being higher in the concomitant coronary artery bypass group (P = .03). All groups were predominantly diagnosed with idiopathic pulmonary fibrosis. The proportion of patients with chronic obstructive pulmonary disease was greatest in the group not requiring revascularization (P = .001). Patients with previous CABG were more likely to receive a single lung transplant than a double one (21 versus 4; P = .054). Length of stay, posttransplant survival, and postoperative adverse events were similar among all groups. CONCLUSIONS: Results suggest that preoperative or intraoperative revascularization does not negatively affect survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Transplante de Pulmão/mortalidade , Intervenção Coronária Percutânea , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/cirurgia , Idoso , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida
16.
Ann Thorac Surg ; 110(1): e31-e33, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31926159

RESUMO

Characterized by pleural and subpleural fibrosis with alveolar septal elastosis, pleuroparenchymal fibroelastosis is a rare restrictive lung disease. Symptoms are often subtle, including dyspnea, cough, and weight loss; while acute presentations of spontaneous pneumothorax have been recorded. We report a patient who developed a spontaneous hemothorax, who upon evacuation of the chest was found to have a hemorrhagic lower lobe mass consistent with pleuroparenchymal fibroelastosis. Various conditions are associated with pleuroparenchymal fibroelastosis, suggesting chronic lung injury as a factor in pathogenesis. Hemothorax of this magnitude with relatively no known inciting risk factors, represents an exceptionally rare case presentation.


Assuntos
Hemotórax/etiologia , Pulmão/diagnóstico por imagem , Pleura/diagnóstico por imagem , Doenças Pleurais/complicações , Fibrose Pulmonar/complicações , Adulto , Biópsia , Fibrose/complicações , Fibrose/diagnóstico , Hemotórax/diagnóstico , Hemotórax/cirurgia , Humanos , Masculino , Doenças Pleurais/diagnóstico , Fibrose Pulmonar/diagnóstico , Toracoscopia , Tomografia Computadorizada por Raios X
17.
Lancet Respir Med ; 8(2): 147-157, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578169

RESUMO

BACKGROUND: At present, no approved pharmacotherapies are available for unclassifiable interstitial lung disease (ILD), which is characterised by progressive fibrosis of the lung. We aimed to assess the efficacy and safety of pirfenidone in patients with progressive fibrosing unclassifiable ILD. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 70 centres in Australia, Belgium, Canada, Czech Republic, Denmark, Germany, Greece, Ireland, Israel, Italy, Poland, Portugal, Spain, and the UK. Eligible patients (aged ≥18-85 years) had progressive fibrosing unclassifiable ILD, a percent predicted forced vital capacity (FVC) of 45% or higher and percent predicted carbon monoxide diffusing capacity (DLco) of 30% or higher, more than 10% fibrosis on high-resolution CT, and a high-resolution CT from the previous 12 months. Patients were randomly assigned (1:1) to 2403 mg oral pirfenidone daily or placebo using a central validated interactive voice or web-based response system, stratified by concomitant mycophenolate mofetil use and presence or absence of interstitial pneumonia with autoimmune features. Investigators, site personnel, and patients were masked to treatment assignment. The primary endpoint was mean predicted change in FVC from baseline over 24 weeks, measured by daily home spirometry. Secondary endpoints were change in FVC measured by site spirometry, proportion of patients who had a more than 5% or more than 10% absolute or relative decline in percent predicted FVC measured by clinic-based spirometry, change in percent predicted DLco, change in 6-min walk distance (6MWD), change in University of California San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) score, change in Leicester Cough Questionnaire score, change in cough visual analogue scale, and changes in total and subscores of the St George's Respiratory Questionnaire (SGRQ), all of which were compared with baseline. Additional secondary endpoints included proportion of patients who had non-elective hospitalisation (respiratory and all-cause) and acute exacerbations, and progression-free survival. Efficacy was analysed in the intention-to-treat (ITT) population, which included all randomly assigned patients. Safety was assessed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03099187, and is no longer recruiting. FINDINGS: Between May 15, 2017, and June 5, 2018, 253 patients were randomly assigned to receive 2403 mg pirfenidone (n=127) or placebo (n=126) and were included in the ITT analysis set. Analysis of the primary endpoint was affected by intraindividual variability in home spirometry values, which prevented application of the prespecified statistical model. Over 24 weeks, predicted median change in FVC measured by home spirometry was -87·7 mL (Q1-Q3 -338·1 to 148·6) in the pirfenidone group versus -157·1 mL (-370·9 to 70·1) in the placebo group. Over 24 weeks, predicted mean change in FVC measured by site spirometry was lower in patients given pirfenidone than placebo (treatment difference 95·3 mL [95% CI 35·9 to 154·6], p=0·002). Compared with the placebo group, patients in the pirfenidone group were less likely to have a decline in FVC of more than 5% (odds ratio [OR] 0·42 [95% CI 0·25 to 0·69], p=0·001) or more than 10% (OR 0·44 [0·23 to 0·84], p=0·011). At week 24, mean change in DLco from baseline was -0·7% (SD 7·1) for the pirfenidone group and -2·5% (8·8) for the placebo group, and mean change in 6MWD from baseline was -2·0 m (68·1) for the pirfenidone group and -26·7 m (79·3) for the placebo group. Changes from baseline in UCSD-SOBQ, Leicester Cough Questionnaire score, cough visual analogue scale, and SGRQ scores were similar between the pirfenidone and placebo groups at week 24. Analysis of acute exacerbations, hospital admissions, and time to death from respiratory causes during the study yielded no meaningful results due to a small number of events. No differences in progression-free survival were identified between the pirfenidone and placebo groups, irrespective of the definition of progression-free survival used. Treatment-emergent adverse events were reported in 120 (94%) of 127 patients in the pirfenidone group and 101 (81%) of 124 patients in the placebo group. Serious treatment-emergent adverse events were reported in 18 (14%) patients in the pirfenidone group and 20 (16%) patients in the placebo group. The most common treatment-related treatment-emergent adverse events were gastrointestinal disorders (60 [47%] in the pirfenidone group vs 32 [26%] in the placebo group), fatigue (16 [13%] vs 12 [10%]), and rash (13 [10%] vs nine [7%]). INTERPRETATION: Although the planned statistical model could not be applied to the primary endpoint data, analysis of key secondary endpoints suggests that patients with progressive fibrosing unclassifiable ILD could benefit from pirfenidone treatment, which has an acceptable safety and tolerability profile. These findings support further investigation of pirfenidone as an effective treatment for patients with progressive fibrotic unclassifiable ILD. FUNDING: F Hoffmann-La Roche.


Assuntos
Doenças Pulmonares Intersticiais/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Piridonas/uso terapêutico , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Europa (Continente) , Feminino , Humanos , Pulmão/efeitos dos fármacos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Intervalo Livre de Progressão , Fibrose Pulmonar/complicações , Fibrose Pulmonar/mortalidade , Testes de Função Respiratória , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos
18.
J Card Surg ; 35(2): 470-472, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765012

RESUMO

Concomitant cardiac surgery at the time of lung transplantation while uncommon has been shown to have acceptable morbidity and mortality. We present a case of a 66-year-old man with a history of interstitial pulmonary fibrosis with end-stage lung disease who presented with moderate aortic stenosis and severe aortic regurgitation. He underwent a bioprosthetic surgical aortic valve replacement at the time of bilateral orthotopic lung transplant and recovered without any major complications.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Transplante de Pulmão/métodos , Fibrose Pulmonar/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Insuficiência da Valva Aórtica/complicações , Estenose da Valva Aórtica/complicações , Humanos , Masculino , Fibrose Pulmonar/complicações , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Intern Med ; 59(5): 695-700, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588081

RESUMO

A 26-year-old man with a history of bronchial asthma was found to have high-density shadows along the bronchovascular bundle and in the subpleural area on computed tomography of the chest. Surgical lung biopsy specimens from the right S5 showed fibroelastosis in the subpleural and central airway area with alveolar destruction. He was diagnosed with airway-centered fibroelastosis of unknown cause after multidisciplinary discussions. The patient developed pulmonary hypertension and died 6 years later. The patient was younger in comparison to patients in earlier reports and had more obvious subpleural fibroelastic lesions in the upper lobes than in previously described cases.


Assuntos
Hipertensão Pulmonar/complicações , Doenças Pleurais/complicações , Doenças Pleurais/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , Adulto , Arteriosclerose/patologia , Asma/patologia , Humanos , Hipertensão Pulmonar/patologia , Pulmão/patologia , Transplante de Pulmão , Masculino , Tomografia Computadorizada por Raios X
20.
Am J Physiol Lung Cell Mol Physiol ; 318(2): L407-L418, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644311

RESUMO

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.


Assuntos
Antibacterianos/efeitos adversos , Displasia Broncopulmonar/complicações , Lesão Pulmonar/induzido quimicamente , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/patologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Líquido da Lavagem Broncoalveolar , Displasia Broncopulmonar/fisiopatologia , Citocinas/metabolismo , Feminino , Granulócitos/metabolismo , Hiperóxia/complicações , Hiperóxia/fisiopatologia , Inflamassomos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Pulmão/patologia , Lesão Pulmonar/microbiologia , Lesão Pulmonar/fisiopatologia , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/microbiologia , Análise de Sobrevida , Remodelação Vascular/efeitos dos fármacos
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