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BACKGROUND AND AIMS: The recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether PAP termination is associated with an increased incidence of major adverse CV events (MACE) compared with adherent PAP continuation. METHODS: Data from the Pays de la Loire Sleep Cohort were linked to the French national health insurance database to identify incident MACE (composite outcome of mortality, stroke and cardiac diseases), and CV active drug (lipid-lowering, antihypertensive and antiplatelet drugs, beta-blockers) adherence (medication possession ratio ≥80%). The association of PAP termination with MACE was evaluated using a time-dependent survival Cox model, with adjustment for confounders including CV active drug status. RESULTS: After a median follow-up of 8 years, 969 of 4188 included patients (median age 58 years, 69.6% men) experienced MACE, 1485 had terminated PAP while 2703 continued PAP with at least 4 hours/night use. 38% of patients were adherent to all CV drugs in the PAP continuation group versus 28% in the PAP termination group (p<0.0001). After adjustment for confounders, PAP termination was associated with an increased risk of MACE (HR (95% CI): 1.39 (1.20 to 1.62); p<0.0001). PAP termination was not associated with incident heart failure and coronary artery disease. CONCLUSIONS: In this multicentre clinical-based cohort involving 4188 patients with OSA, PAP termination compared with adherent PAP continuation was associated with an increased risk of MACE. More research is needed to determine whether support programmes on PAP adherence could improve CV outcomes.
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Background: The role of obesity on dyspnea in chronic obstructive pulmonary disease (COPD) patients remains unclear. We aimed to provide an assessment of dyspnea in COPD patients according to their Body Mass Index (BMI) and to investigate the impact of obesity on dyspnea according to COPD severity. Methods: One hundred and twenty seven COPD patients with BMI ≥ 18.5 kg/m² (63% male, median (interquartile range) post bronchodilator forced expiratory volume of 1 second (post BD FEV1) at 51 (34-66) % pred) were consecutively included. Dyspnea was assessed by mMRC (Modified medical research council) scale. Lung function tests were recorded, and emphysema was quantified on CT-scan (computed tomography-scan). Results: Twenty-five percent of the patients were obese (BMI ≥ 30kg/m²), 66% of patients experienced disabling dyspnea (mMRC ≥ 2). mMRC scores did not differ depending on BMI categories (2 (1-3) for normal weight, 2 (1-3) 1 for overweight and 2 (1-3) for obese patients; p = 0.71). Increased mMRC scores (0-1 versus 2-3 versus 4) were associated with decreased post BD-FEV1 (p < 0.01), higher static lung hyperinflation (inspiratory capacity/total lung capacity (IC/TLC), p < 0.01), reduced DLCO (p < 0.01) and higher emphysema scores (p < 0.01). Obese patients had reduced static lung hyperinflation (IC/TLC p < 0.01) and lower emphysema scores (p < 0.01) than non-obese patients. mMRC score increased with GOLD grades (1-2 versus 3-4) in non-obese patients but not in obese patients, in association with a trend towards reduced static lung hyperinflation and lower emphysema scores. Conclusion: By contrast with non-obese patients, dyspnea did not increase with spirometric GOLD grades in obese patients. This might be explained by a reduced lung hyperinflation related to the mechanical effects of obesity and a less severe emphysema in severe COPD patients with obesity.
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Índice de Massa Corporal , Dispneia , Pulmão , Obesidade , Doença Pulmonar Obstrutiva Crônica , Índice de Gravidade de Doença , Humanos , Masculino , Dispneia/fisiopatologia , Dispneia/etiologia , Dispneia/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Obesidade/complicações , Obesidade/fisiopatologia , Obesidade/diagnóstico , Feminino , Idoso , Pessoa de Meia-Idade , Volume Expiratório Forçado , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/diagnóstico , Fatores de Risco , EspirometriaRESUMO
BACKGROUND: The healthy adherer effect has gained increasing attention as potential source of bias in observational studies examining the association of positive airway pressure (PAP) adherence with health outcomes in OSA. RESEARCH QUESTION: Is adherence to PAP associated with healthy behaviors and health care resource use prior to device prescription? STUDY DESIGN AND METHODS: Data from the IRSR Pays de la Loire Sleep Cohort were linked to health administrative data to identify proxies of heathy behaviors, including adherence to cardiovascular (CV) drugs (medical possession ratio), cancer screening tests, influenza vaccination, alcohol and smoking consumption, and drowsiness-related road accidents during the 2 years preceding PAP onset in patients with OSA. Multivariable regression analyses were conducted to evaluate the association of heathy behaviors with subsequent PAP adherence. Health care resource use was evaluated according to subsequent PAP adherence. RESULTS: We included 2,836 patients who had started PAP therapy between 2012 and 2018 (65% of whom were PAP adherent with mean daily use ≥ 4 h/night). Being adherent to CV active drugs (medical possession ratio ≥ 80%) and a person who does not smoke were associated with a higher likelihood of PAP adherence (OR, 1.43; 95% CI, 1.15-1.77 and OR, 1.37; 95% CI, 1.10-1.71, respectively). Patients with no history of drowsiness-related road accidents were more likely to continue PAP (OR, 1.39; 95% CI, 1.04-1.87). Patients who were PAP adherent used less health care resources 2 years before PAP initiation than patients who were nonadherent (mean number of outpatient consultations: 19.0 vs 17.2, P = .003; hospitalization days: 5.7 vs 5.0; P = .04; ED visits: 30.7% vs 24.0%, P = .0002, respectively). INTERPRETATION: Patients who adhere to PAP therapy for OSA were more health-seeking and used less health care resources prior to device initiation than patients who were nonadherent. Until the healthy adherer effect associated with PAP adherence is better understood, caution is warranted when interpreting the association of PAP adherence with CV health outcomes and health care resource use in nonrandomized cohorts.
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Purpose: The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV1 decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state. Patients and Methods: Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC <300/mm3 and high BEC ≥300/mm3. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota. Results: Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p<0.001) and more pronounced cough and sputum (p<0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition. Conclusion: In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.
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Eosinofilia , Microbiota , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Eosinófilos , Progressão da Doença , Sistema Respiratório , Contagem de Leucócitos , Escarro/microbiologiaRESUMO
BACKGROUND: Bronchiectasis is a chronic airway disease characterized by permanent and irreversible abnormal dilatation of bronchi. Several studies have reported the development of bronchiectasis after renal transplantation (RT), but no prospective study specifically assessed bronchiectasis in this population. This study aimed to compare features of patients with bronchiectasis associated with RT to those with idiopathic bronchiectasis. METHODS: Nineteen patients with bronchiectasis associated with RT (RT-B group) and 23 patients with idiopathic bronchiectasis (IB group) were prospectively included in this monocentric cross-sectional study. All patients underwent clinical, functional, laboratory, and CT scan assessments. Sputum was collected from 25 patients (n = 11 with RT-B and n = 14 with IB) and airway microbiota was analyzed using an extended microbiological culture. RESULTS: Dyspnea (≥ 2 on mMRC scale), number of exacerbations, pulmonary function tests, total bronchiectasis score, severity and prognosis scores (FACED and E-FACED), and quality of life scores (SGRQ and MOS SF-36) were similar in the RT-B and IB groups. By contrast, chronic cough was less frequent in the RT-B group than in the IB group (68% vs. 96%, p = 0.03). The prevalence and diversity of the airway microbiota in sputum were similar in the two groups. CONCLUSION: Clinical, functional, thoracic CT scan, and microbiological characteristics of bronchiectasis are overall similar in patients with IB and RT-B. These results highlight that in RT patients, chronic respiratory symptoms and/or airway infections should lead to consider the diagnosis of bronchiectasis. Further studies are required to better characterize the pathophysiology of RT-B including airway microbiota, its incidence, and impact on therapeutic management.
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Bronquiectasia , Transplante de Rim , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Transversais , Transplante de Rim/efeitos adversos , Qualidade de Vida , Bronquiectasia/complicaçõesRESUMO
BACKGROUND: Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life. METHODS: This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ). RESULTS: Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis. CONCLUSIONS: CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016).
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Fibrose Cística , Qualidade de Vida , Masculino , Adulto , Humanos , Feminino , Adulto Jovem , Tosse/etiologia , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Escarro , Estudos Prospectivos , Estudos Transversais , Projetos Piloto , Inquéritos e Questionários , DispneiaRESUMO
BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.
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Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Qualidade de Vida , Pressão Positiva Contínua nas Vias Aéreas , Pressão Sanguínea/fisiologia , Projetos de PesquisaRESUMO
RATIONALE: Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma. PATIENT CONCERNS: A 72-years-old male, treated for multiple myeloma with dexamethasone, pomalidomide and daratumumab, presented dyspnea, hypoxemia, biological inflammatory syndrome, ground glass opacities on computed tomography scan (CT-scan) and lymphocytic and eosinophilic alveolitis, with no specific cytologic or microbiological findings, 2 months after pomalidomide initiation. INTERVENTION AND OUTCOME: Antibiotics were started after bronchoscopy. No improvement was noted in dyspnea and biological inflammatory syndrome after 5 days of treatment. Pomalidomide was then discontinued, with continuation of Daratumumab-Dexamethasone, resulting in a rapid recovery of symptoms and CT-scan anomalies. No recurrence of dyspnea was observed during the 15 months of follow-up. DIAGNOSES: Pomalidomide-induced lung injury. LESSONS: Pomalidomide-induced lung injury is a rare and serious adverse event that can occur early after Pomalidomide introduction. As pomalidomide use is increasing, the identification of drug toxicity as a possible cause of lung injury appears important. We report a rapid recovery of symptoms and CT-scan anomalies after pomalidomide discontinuation.
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Lesão Pulmonar , Mieloma Múltiplo , Masculino , Humanos , Idoso , Mieloma Múltiplo/tratamento farmacológico , Lesão Pulmonar/etiologia , Dexametasona/uso terapêutico , Dispneia/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Survival improvement in cystic fibrosis (CF) is associated with more frequent long-term complications, including CF related bone disease (CFBD). Impact of CFBD on global health outcome remains poorly described. We aimed to assess the relationship between low bone mineral density (BMD) and spinal pain, disability, and quality of life in CF adult patients. This monocentric cross-sectional study with prospective data collection was conducted from November 2016 to December 2019 in the Department of Respiratory Diseases at the University Hospital of Reims (NCT02924818). BMD was assessed by X-ray absorptiometry (DXA). Disability was assessed by the Health Assessment Questionnaire (HAQ). Quality of life was assessed by both the St George's Respiratory Questionnaire and the Cystic Fibrosis Questionnaire for teenagers and adults (CFQ 14+). Forty patients were analyzed, 68% of men, with a median age of 25 years, a median body mass index of 21 kg/m² and a median FEV1% of 54%. Nine patients (23%) had spinal pain. Ten patients (25%) had a low BMD. Compared with patients with normal BMD, patients with low BMD had a significantly lower BMI (22 vs 19 kg/m²; Pâ =â .006) and less vitamin D supplementation (33% vs 0%; Pâ =â .035). Low BMD was not associated with spinal pain, disability and quality of life. Low BMD is frequent in CF, affecting 1-quarter of adult patients. No significant association was found between low BMD and spinal pain, disability or quality of life.
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Doenças Ósseas Metabólicas , Fibrose Cística , Masculino , Adolescente , Humanos , Adulto , Fibrose Cística/complicações , Densidade Óssea , Projetos Piloto , Estudos Transversais , Relevância Clínica , Qualidade de Vida , Doenças Ósseas Metabólicas/complicações , Absorciometria de FótonRESUMO
BACKGROUND: Tracheobronchopathia osteochondroplastica (TO) is a rare condition of unknown etiology. TO is characterized by submucosal nodules, with or without calcifications, protruding in the anterolateral walls of the trachea and proximal bronchi. The objective of this study was to describe TO features and associated comorbidities in a series of patients. METHODS: Patients suffering from TO were retrospectively included by investigators from the Groupe d'Endoscopie Thoracique et Interventionnelle Francophone (GETIF). Demographic, clinical, comorbidities, bronchoscopic, functional, and radiological characteristics, and outcomes were recorded and analyzed. RESULTS: Thirty-six patients were included (69% male with a mean of 65 ± 12 years). Chronic symptoms were described by 81% of patients including cough (74%) and dyspnea on exertion (74%). TO was associated with COPD in 19% of the cases and gastroesophageal reflux disease in 6%. A mild to severe airflow obstruction was present in 55% of the cases. CT scan showed tracheal submucosal nodules in 93% of patients and tracheal stenosis in 17%. Bronchoscopy identified TO lesions in the trachea in 65% of the cases, and 66% of them were scattered. A bronchoscopic reevaluation was performed in 7 cases, 9 ± 14 months [1-56] after initial diagnosis, and showed the stability of lesions in all cases. Three patients underwent interventional bronchoscopic treatment. CONCLUSION: The diagnosis of TO relies on typical bronchoscopic findings and can be evoked on a CT scan. Histologic diagnosis can be useful in atypical cases for differential diagnosis. Given its low consequences in terms of symptoms, lung functions, and evolution, no treatment is usually required.
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Osteocondrodisplasias , Doenças da Traqueia , Feminino , Humanos , Masculino , Broncoscopia , Osteocondrodisplasias/complicações , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/epidemiologia , Estudos Retrospectivos , Doenças da Traqueia/complicações , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/epidemiologia , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: To explore the impact of improved intensive care for COVID-19 patients on the prevalence of post-intensive care syndrome (PICS). DESIGN: Ambispective cohort study. PATIENTS: Post-intensive care unit COVID-19 patients from the first and second waves of COVID-19. METHODS: Patients were evaluated at 6 months after infection. PICS was defined as the presence of a 1-min sit-to-stand test (1STS) score < 2.5th percentile or a Symbol Digit Modalities Test (SDMT) below the 2 standard deviation cut-off, or a Hospital Anxiety and Depression Scale score ≥ 11. RESULTS: A total of 60 patients were included (34 from wave 1 and 26 from wave 2). Intensive care unit management improved between waves, with shorter duration of orotracheal intubation (7 vs 23.5 days, p = 0.015) and intensive care unit stay (6 vs 9.5 days, p = 0.006) in wave 2. PICS was present in 51.5% of patients after wave 1 and 52% after wave 2 (p = 0.971). Female sex and diabetes were significantly associated with PICS by multivariate analysis. CONCLUSION: Approximately half of post-intensive care unit COVID-19 patients have 1 or more impairments consistent with PICS at 6 months, with an impact on quality of life and participation. Improved intensive care unit management was not associated with a decrease in the prevalence of PICS. Identification of patients at risk, particularly women and diabetic patients, is essential. Further studies of underlying mechanisms and the need for rehabilitation are essential to reduce the risk of PICS.
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COVID-19 , Feminino , Humanos , Estudos de Coortes , COVID-19/epidemiologia , Cuidados Críticos , Estado Terminal , Unidades de Terapia Intensiva , Prevalência , Qualidade de Vida , MasculinoRESUMO
BACKGROUND: The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. METHODS: Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). RESULTS: Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management. CONCLUSIONS AND CLINICAL IMPLICATION: We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840.
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COVID-19 , Insuficiência Respiratória , Sarcopenia , COVID-19/complicações , Análise por Conglomerados , Humanos , Fenótipo , Estudos Prospectivos , Qualidade de Vida , SARS-CoV-2RESUMO
BACKGROUND: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. METHODS: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. RESULTS: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. CONCLUSION: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.
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BACKGROUND: Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We conducted a cross-sectional study to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity. METHODS: One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m2 were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed. RESULTS: Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, p < 0.001), lower lung volumes including Expiratory Reserve Volume (42 ± 28% vs 54 ± 27%, p = 0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, p < 0.001) and Forced expiratory volume in one second (95 ± 13 vs 105 ± 15%, p = 0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m2, p = 0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p = 0.012) and android region (52 ± 4 vs 51 ± 4%, p = 0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea. CONCLUSION: Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated.
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Dispneia , Força da Mão , Composição Corporal , Estudos Transversais , Dispneia/etiologia , Feminino , Humanos , Pulmão , Masculino , Obesidade/complicações , Estudos ProspectivosRESUMO
BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.
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Glucocorticoides , Fibrose Pulmonar Idiopática , Adulto , Ciclofosfamida/efeitos adversos , Método Duplo-Cego , Glucocorticoides/efeitos adversos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Resultado do TratamentoRESUMO
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.
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RATIONALE: Thoracic endometriosis is a rare disorder that can involve airways, pleura and lung parenchyma. It is the most frequent form of extra-abdominopelvic endometriosis. Multiple lung cavitations are a rare feature of thoracic endometriosis. PATIENT CONCERNS: A 46-year-old woman was referred to our hospital after incidental finding of multiple pulmonary cavitations with surrounding areas of ground glass opacity on a thoraco-abdominal computed tomography-scan performed for abdominal pain. Retrospectively, the patient also reported mild hemoptysis occurring 4 months ago. DIAGNOSES: Positron emission tomography-computed tomography scan revealed moderate and homogeneous [18F] fluoro-2-deoxy-D-glucose (18F-FDG) uptake in pulmonary cavitations (maximum standardized uptake value 5.7). The diagnosis of thoracic endometriosis was confirmed by histological examination of surgical resection of a left lower lobe cavitation. INTERVENTIONS AND OUTCOME: Gonadotropin-releasing hormone analogues associated with add-back therapy was started. Four months after initiating pharmacological treatment, the chest computed tomography-scan showed a dramatic decrease in lung cavitations size. LESSONS: Thoracic endometriosis is a rare disorder requiring a multidisciplinary management including gynaecologist, pulmonologist, radiologist, nuclear physician, pathologist and thoracic surgeon for early diagnosis and treatment. Our case report highlights that an increased 18F-FDG uptake can be found in thoracic endometriosis syndrome presenting as multiple lung cavitations.
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Endometriose/patologia , Pulmão/patologia , Endometriose/diagnóstico por imagem , Endometriose/cirurgia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease. However, its pathophysiology remains partially elucidated. Epithelial remodeling including alteration of the cilium is a major hallmark of COPD, but specific assessments of the cilium have been rarely investigated as a diagnostic tool in COPD. Here we explore the dysregulation of the ciliary function (ciliary beat frequency (CBF)) and differentiation (multiciliated cells formation in air-liquid interface cultures) of bronchial epithelial cells from COPD (n = 17) and non-COPD patients (n = 15). CBF was decreased by 30% in COPD (11.15 +/- 3.37 Hz vs. 7.89 +/- 3.39 Hz, p = 0.037). Ciliary differentiation was altered during airway epithelial cell differentiation from COPD patients. While the number of multiciliated cells decreased (p < 0.005), the number of primary ciliated cells increased (p < 0.05) and primary cilia were shorter (p < 0.05). Altogether, we demonstrate that COPD can be considered as a ciliopathy through both primary non-motile cilia modifications (related to airway epithelial cell repair and remodeling) and motile cilia function impairment (associated with decrease sputum clearance and clinical respiratory symptoms). These observations encourage considering cilia-associated features in the complex COPD physiopathology and highlight the potential of cilia-derived biomarkers for diagnosis.
RESUMO
BACKGROUND: Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams. METHODS: We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items. RESULTS: Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m2. Mean FEV1% was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school. CONCLUSIONS: Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016.
Assuntos
Fibrose Cística/terapia , Avaliação das Necessidades , Autorrelato , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Adulto JovemRESUMO
The gene cluster region, CHRNA3/CHRNA5/CHRNB4, encoding for nicotinic acetylcholine receptor (nAChR) subunits, contains several genetic variants linked to nicotine addiction and brain disorders. The CHRNA5 single-nucleotide polymorphism (SNP) rs16969968 is strongly associated with nicotine dependence and lung diseases. Using immunostaining studies on tissue sections and air-liquid interface airway epithelial cell cultures, in situ hybridisation, transcriptomic and cytokines detection, we analysed rs16969968 contribution to respiratory airway epithelial remodelling and modulation of inflammation. We provide cellular and molecular analyses which support the genetic association of this polymorphism with impaired ciliogenesis and the altered production of inflammatory mediators. This suggests its role in lung disease development.