RESUMO
BACKGROUND: Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy. METHODS: In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000â mg) or placebo on day 1 and day 15 in addition to MMF (2â g daily) for 6â months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6â months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6â months and safety. FINDINGS: Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6â months in FVC (% predicted) was +1.60 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group. INTERPRETATION: Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.
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Pneumonias Intersticiais Idiopáticas , Doenças Pulmonares Intersticiais , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Ácido Micofenólico/uso terapêutico , Imunossupressores/efeitos adversos , Pulmão , Resultado do Tratamento , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Método Duplo-CegoRESUMO
Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
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Exposição Ocupacional , Sarcoidose , Adulto , Criança , Poeira , Exposição Ambiental/efeitos adversos , Humanos , Exposição Ocupacional/efeitos adversos , Ocupações , TalcoRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties. METHODS AND RESULTS: ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis. CONCLUSION: To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.
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Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/patologia , Interleucina-8/metabolismo , Células-Tronco/metabolismo , Células-Tronco/patologia , Adulto , Células Cultivadas , Estudos de Coortes , Células Endoteliais/fisiologia , Seguimentos , França , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fenótipo , Cultura Primária de Células , Células-Tronco/fisiologiaRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) has an unpredictable course corresponding to various profiles: stability, physiological disease progression and rapid decline. A minority of patients experience acute exacerbations (AEs). A recent study suggested that ozone and nitrogen dioxide might contribute to the occurrence of AE. We hypothesised that outdoor air pollution might influence the natural history of IPF. METHODS: Patients were selected from the French cohort COhorte FIbrose (COFI), a national multicentre longitudinal prospective cohort of IPF (n=192). Air pollutant levels were assigned to each patient from the air quality monitoring station closest to the patient's geocoded residence. Cox proportional hazards model was used to evaluate the impact of air pollution on AE, disease progression and death. RESULTS: Onset of AEs was significantly associated with an increased mean level of ozone in the six preceding weeks, with an HR of 1.47 (95% CI 1.13 to 1.92) per 10 µg/m3 (p=0.005). Cumulative levels of exposure to particulate matter PM10 and PM2.5 were above WHO recommendations in 34% and 100% of patients, respectively. Mortality was significantly associated with increased levels of exposure to PM10 (HR=2.01, 95% CI 1.07 to 3.77) per 10 µg/m3 (p=0.03), and PM2.5 (HR=7.93, 95% CI 2.93 to 21.33) per 10 µg/m3 (p<0.001). CONCLUSION: This study suggests that air pollution has a negative impact on IPF outcomes, corroborating the role of ozone on AEs and establishing, for the first time, the potential role of long-term exposure to PM10 and PM2.5 on overall mortality.
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Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Fibrose Pulmonar Idiopática/etiologia , Idoso , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Feminino , França , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de TempoRESUMO
RATIONALE: Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects. OBJECTIVES: To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT. METHODS: In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account. MEASUREMENTS AND MAIN RESULTS: At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment. CONCLUSIONS: Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
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Bronquiolite Obliterante/terapia , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Etanolaminas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment. METHODS: We performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014. RESULTS: Eight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial. CONCLUSIONS: Bleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.
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Antibióticos Antineoplásicos/efeitos adversos , Bleomicina/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/tratamento farmacológico , Fatores Etários , Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Feminino , Humanos , Pneumonia/mortalidade , Insuficiência Renal/epidemiologiaRESUMO
Bonchoalveolar lavage is a safe and poorly invasive tool with a great diagnostic value particularly in diffuse infiltrative pulmonary diseases (IPD). In specific instances, it allows for a definite diagnosis (alveolar hemorrhage; alveolar proteinosis, lipidoses, infiltrative malignant diseases, opportunistic infections), obviating the need to perform more invasive diagnostic procedures like video-assisted surgical biopsy. In inflammatory IPD, either idiopathic, diagnostic or associated with inhaled antigens or with collagen vascular diseases for instance, it represents a crucial orientation diagnostic tool, considerably narrowing the spectrum of potential differential diagnosis.
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Líquido da Lavagem Broncoalveolar/citologia , Lavagem Broncoalveolar , Doenças Pulmonares Intersticiais/diagnóstico , Lavagem Broncoalveolar/métodos , Diagnóstico Diferencial , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/terapia , PrognósticoRESUMO
BACKGROUND: Activity-related dyspnea is the main contributor to the altered quality of life in diffuse parenchymal lung diseases (DPLD). Instruments pertaining to dyspnea are classified as pertaining to domains of sensory-perceptual experience, affective distress or symptom/disease impact; whether these domains are equally related to lung function impairments remains to be established. OBJECTIVES: They were to assess the relationships between two domains of dyspnea (sensory-perceptual experience and symptom impact) and pulmonary function tests according to their evaluation of ventilatory demand, capacity and drive in patients suffering from DPLD. METHODS: Fifty patients were prospectively enrolled (median age, 58 years; 25 women) and underwent spirometry, body plethysmography, measurements of lung diffusion for carbon monoxide (DLCO) and nitric oxide, maximal airway pressures (capacity and demand assessments), mouth occlusion pressure at 0.1 s (P0.1: respiratory drive assessment) and a 6-min walk test with Borg score assessment (dyspnea: sensory domain). The impact domain of dyspnea was evaluated using the baseline dyspnea index. RESULTS: The sensory domain of dyspnea was linked to demand (CO transfer coefficient, kCO) only, while the impact domain was independently linked to demand and capacity (kCO and forced vital capacity, respectively). Among resting pulmonary function tests, both P0.1 and DLCO allowed the assessment of these two domains of dyspnea. CONCLUSIONS: In DPLD, the sensory-perceptual domain of dyspnea is mainly linked to alterations in ventilatory demand while the impact domain is related to both demand and capacity. DLCO that assesses both demand and capacity and P0.1 were the strongest correlates of dyspnea.
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Dispneia/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Adulto , Idoso , Estudos Transversais , Dispneia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função RespiratóriaRESUMO
BACKGROUND: ATS/ERS Task Force has highlighted that special attention must be paid when FEV1 and FVC are concomitantly decreased (<5th percentile) and the FEV1/FVC ratio is normal (>5th percentile) because a possible cause of this non specific pattern (NSP) is collapse of small airways with normal TLC measured by body plethysmography (>5th percentile). Our objectives were to determine the main lung diseases associated with this pattern recorded prospectively in a lung function testing (LFT) unit, the prevalence of this pattern in our LFT and among the diseases identified, and its development. METHODS: Observational study of routinely collected data selected from our Clinical Database Warehouse. RESULTS: The prevalence of NSP was 841/12 775 tests (6.6%, 95% CI: 6.2 to 7.0%). NSP was mainly associated with seven lung diseases: asthma (prevalence of NSP among asthmatics: 12.6%), COPD/emphysema (prevalence 8.6%), bronchiectasis (12.8%), sarcoidosis (10.7%), interstitial pneumonia (4.0%), pulmonary hypertension (8.9%) and bilateral lung transplantation for cystic fibrosis (36.0%). LFT measurements were described in 185 patients with NSP and indisputable nonoverlapping causes. A moderate defect (FEV1: 66 ± 9% predicted) with mild lung hyperinflation (FRC: 111 ± 27%, RV: 131 ± 33% predicted: suggesting distal airway obstruction) was evidenced whatever the underlying cause. A long term stability of NSP was evidenced in 130/185 patients (70% 95% CI: 64 to 77%). CONCLUSIONS: NSP is observed in asthma, COPD/emphysema, bronchiectasis, sarcoidosis, pulmonary hypertension, interstitial pneumonia and after bilateral lung transplantation and remains stable in the majority of patients.
Assuntos
Volume Expiratório Forçado , Pneumopatias/fisiopatologia , Capacidade Vital , Adulto , Idoso , Asma/fisiopatologia , Bronquiectasia/fisiopatologia , Estudos Transversais , Fibrose Cística/fisiopatologia , Fibrose Cística/cirurgia , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Estudos Longitudinais , Doenças Pulmonares Intersticiais/fisiopatologia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/fisiopatologia , Sarcoidose Pulmonar/fisiopatologia , Capacidade Pulmonar TotalRESUMO
OBJECTIVES: The first objective of our study was to assess whether patients diagnosed with cardio-respiratory disorders report overestimation or underestimation on recall (Medical Research Council (MRC) dyspnea scale) of their true functional capacity (walked distance during a 6-minute walk test (6MWT)). The second objective was to assess whether the measurement of breathlessness at the end of a 6MWT (Borg score) may help to identify dyspneic patients on recall. METHODS: The 6MWTs of 746 patients aged from 40 to 80 years who were diagnosed with either chronic obstructive pulmonary disease (COPD, n = 355), diffuse parenchymal lung disease (n = 140), pulmonary vascular diseases (n = 188) or congestive heart failure (n = 63) were selected from a prospective Clinical Database Warehouse. RESULTS: The percentage of patients who overestimated (MRC ≤ 2 with distance < lower limit of normal (LLN), 61/746, 8%; 95% confidence interval (CI): 6 to 10%) or underestimated (MRC > 2 with distance ≥LLN, 121/746, 16%; 95%CI: 14 to 19%) on recall their capacity was elevated. The overestimation seemed related to self-limitation, while the underestimation seemed related to patients who "work through" their breathing discomfort. These two latter groups of patients were mainly diagnosed with COPD. A Borg dyspnea score >3 (upper limit of normal) at the end of the 6MWT had 84% specificity for the prediction of a MRC score >1. CONCLUSION: Almost one fourth of patients suffering from cardio-pulmonary disorders overestimate or underestimate on recall their true functional capacity. An elevated Borg dyspnea score at the end of the 6MWT has a good specificity to predict dyspnea on recall.
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Dispneia/diagnóstico , Tolerância ao Exercício , Insuficiência Cardíaca/diagnóstico , Hipertensão Pulmonar/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Embolia Pulmonar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Dispneia/etiologia , Teste de Esforço , Feminino , Insuficiência Cardíaca/complicações , Humanos , Hipertensão Pulmonar/complicações , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Doença Pulmonar Obstrutiva Crônica/complicações , Embolia Pulmonar/complicações , Autorrelato , Sensibilidade e Especificidade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Fibrogenesis during idiopathic pulmonary fibrosis (IPF) is strongly associated with abnormal vascular remodeling. Respective abundance of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair and potentially serve as biomarkers of the disease. OBJECTIVES AND METHODS: We postulated that CEC and EPC subtypes might be differently modulated in IPF. Sixty-four consecutive patients with newly diagnosed IPF were prospectively enrolled and compared to thirteen healthy volunteers. CEC were counted with immunomagnetic CD146-coated beads; progenitors CD34+45(dim)/CD34+133+/CD34+KDR+were assessed through flow cytometry and EPC (colony-forming-units-Endothelial Cells, CFU-EC, and endothelial colonies forming cells, ECFC) were quantified by cell culture assays. RESULTS: IPF patients were characterized by a marked increase in CEC associated to an EPC defect: both CD34(+)KDR(+) cells and CFU-EC were decreased versus controls. Moreover, in IPF subjects with a low diffusing capacity of the lung for carbon monoxide (DL(CO)) < 40 %, CFU-EC and ECFC were higher compared to those with DL(CO) > 40 %. Finally, ECFC were negatively correlated with DL(CO). During an 18 month follow up, CEC levels increased in patients with exacerbation, including those who died during follow up. Finally, ECFC from patients with exacerbation proliferative potential was strongly increased. CONCLUSION: IPF is basically associated with both a vascular injury and a repair defect. This study highlights an adaptative process of EPC mobilization in the most severe forms of IPF, that could reflect enhanced homing to the pulmonary vasculature, which clinical consequences remain to be determined.
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Movimento Celular , Células Endoteliais/patologia , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/patologia , Células-Tronco/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Contagem de Células , Demografia , Progressão da Doença , Células Endoteliais/metabolismo , Feminino , Citometria de Fluxo , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Células-Tronco/metabolismoRESUMO
OBJECTIVES: Obesity has been associated with a lesser degree of asthma control that may be biased by other comorbidities. The objectives of this cross-sectional study were to describe resting and activity-related dyspnea complaints according to the presence of obesity-related comorbidities (asymptomatic airway hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit both resting and activity-related dyspnea, independently of the presence of asthma. METHODS: Severely obese (body mass index (BMI) > 35 kg m(-2)) women prospectively underwent description of resting and activity-related dyspnea (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function testing (spirometry, absolute lung volumes, and methacholine challenge test), oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean women without airway hyperresponsiveness were enrolled. RESULTS: Resting dyspnea complaints were significantly more prevalent in obesity (prevalence 41%) than in healthy lean women (prevalence 3%). Chest tightness and the need for deep inspirations were independently associated with both asthma and GERD while wheezing and cough were related to asthma only in obese women. Activity-related dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did not affect dyspneic complaints. CONCLUSIONS: In severely obese women referred for bariatric surgery, resting dyspnea complaints are observed in association with asthma or GERD, while activity-related dyspnea was mainly related to obesity only. Consequently, asthma does not explain all respiratory complaints of obese women.
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Dispneia/epidemiologia , Obesidade/epidemiologia , Adulto , Asma/epidemiologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/epidemiologia , Hiper-Reatividade Brônquica/fisiopatologia , Comorbidade , Estudos Transversais , Dispneia/fisiopatologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Pessoa de Meia-Idade , Atividade Motora , Obesidade/fisiopatologia , Testes de Função Respiratória , Descanso , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Adulto JovemRESUMO
Sarcoidosis is an independent risk factor for venous thromboembolism (VTE). However, the characteristics and clinical evolution of sarcoidosis patients presenting a VTE (sarcoidosis/VTE group) in the course of their disease are not known. Consequently, if VTE occurrence is associated with a more severe disease is still pending. We conducted a retrospective case-control study of sarcoidosis/VTE patients compared to matched sarcoidosis controls without VTE in two French tertiary centers, analysed and compared the clinical, biological, functional, imaging and evolutive profiles of the two groups. Sixty-one patients were included with at least one episode of VTE during course of sarcoidosis. At sarcoidosis onset (before/at the time of VTE occurrence) the number of affected organs, radiological stages and pulmonary functional tests were not significantly different between the two groups. In contrast, we found that sarcoidosis/VTE patients required more frequently a systemic immunosuppressive therapy (corticosteroids and/or immunosuppressors, 79% versus 58%; p = 0.008). The functional course was also poorer in sarcoidosis/VTE patients with a more frequent decrease in functional vital capacity (33% versus 18% in sarcoidosis/VTE patients and controls, respectively, p = 0.008). Finally, sarcoidosis/VTE patients presented more frequently with pulmonary hypertension (10% versus 1% in patients and controls, respectively, p = 0.006), and their survival was significantly worse (log-rank p <0.001). The occurrence of VTE during sarcoidosis is associated with a more severe disease and a poorer prognosis. The occurrence of VTE during sarcoidosis might signal a more inflammatory and/or evolutive disease in sarcoidosis/VTE patients and should be taken in consideration when designing therapeutic strategies for them.
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Sarcoidose , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Prognóstico , Estudos de Casos e Controles , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/epidemiologiaRESUMO
Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.
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Dióxido de Carbono/sangue , Capacidade de Difusão Pulmonar/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitorização Transcutânea dos Gases Sanguíneos , Estudos Transversais , Dispneia/fisiopatologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico/fisiologia , Espaço Morto Respiratório/fisiologia , Volume de Ventilação Pulmonar/fisiologiaRESUMO
BACKGROUND: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis. METHODS: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. VATS-LB was proposed after initial multidisciplinary discussion. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after the operation, postoperative pulmonary function, quality of life, and pain. RESULTS: A definite diagnosis was reached in 87 patients (84.4%), and 16 remained unclassifiable (15.6%). After VATS-LB, the hypothesized diagnosis changed in 65 patients (63.1%) and treatment changed in 41 patients (39.8%). One patient died of acute exacerbation. In-hospital complications were predicted by a shorter preoperative 6-minute walking test distance and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months, whereas forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% of patients at 1 month and in 2% at 3 months. CONCLUSIONS: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause, with good patient survival in ILD referral centers.
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Doenças Pulmonares Intersticiais , Cirurgia Torácica Vídeoassistida , Humanos , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/cirurgia , Biópsia/métodos , Pulmão/patologiaAssuntos
Doença Celíaca/complicações , Linfoma de Células T Associado a Enteropatia/patologia , Pulmão/patologia , Linfócitos T/patologia , Adulto , Idoso , Doença Celíaca/patologia , Células Clonais/patologia , Linfoma de Células T Associado a Enteropatia/complicações , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fenótipo , Falha de TratamentoRESUMO
(1) Background: Systemic granulomatosis developed in a context of malignancy has already been reported. Our objective was to describe the clinical, radiological, functional, biological, and evolutive characteristics of sarcoidosis-like cancer-associated granulomatosis (SLCAG) and to compare them to those of sarcoidosis. (2) Methods: 38 patients with a biopsy-proven SLCAG developed after a diagnostic of malignancy were included. The control group consisted of sarcoidosis patients matched for age, sex, and radiologic stage. Clinical, biological, physiological, radiological, and outcome data were collected. (3) Results: The mean age of SLCAG patients was 51 ± 14 years. They were diagnosed within 15 ± 14 months of the cancer diagnosis (breast cancer most frequently). All SLCAG patients presented a thoracic involvement, extrathoracic locations were observed in 32% of subjects. SLCAG was more often asymptomatic than sarcoidosis (p < 0.0001). During follow-up, systemic treatment was less often required in SLCAG than in sarcoidosis (58% vs. 32%, p = 0.04 respectively) and SLCAG were characterized by a significantly less severe progression profile according to the Sarcoid Clinical Activity Classification, with a complete recovery more frequent at 5 years (p = 0.03). (4) Conclusion: This case-control study shows that SLCAG differs from sarcoidosis with a significantly more benign course. These results might argue for true differences in the physiopathology, which remain to be elucidated.
RESUMO
BACKGROUND: Low income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF. METHODS: Patients were selected from the French national prospective cohort COFI. Patients' income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as "low income" vs. "higher income" depending on whether their annual income was estimated to be < or ≥18 170 /year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis. RESULTS: 200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24-2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006-2.23, p = 0.049). CONCLUSIONS: Low income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.
Assuntos
Fibrose Pulmonar Idiopática , Renda/classificação , Pobreza , Medicamentos Biossimilares , Intervalo Livre de Doença , Exposição Ambiental/efeitos adversos , França , Fibrose Pulmonar Idiopática/economia , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Exposição Ocupacional/efeitos adversos , Material Particulado/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Capacidade VitalRESUMO
Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up. Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed. Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28-40) vs. 40 months (CI 95%: 33-72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival. Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.
RESUMO
(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (≤15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (±2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3-44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0-32), resulting in mostly mild (18; 35.3%) and rarely severe (2; 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood.