Abstract
Background
There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial ...lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database.
Methods
The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD.
Results
We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan–Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622–54,287) and the median annual cost per patient was €18,362 (6856–52,026), of which €11,784 (3003–42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests.
Conclusions
This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services.
Trial registration
ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019—Retrospectively registered,
https://clinicaltrials.gov/ct2/show/NCT03858842
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The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their ...disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported.
In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders.
The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients.
Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs.
ClinicalTrials.gov: No: NCT01225601 .
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and ...associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial.
Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m
), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints.
Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m
, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m
(nintedanib: - 123.4, - 83.3, - 46.9 mL/year, respectively; placebo: - 229.5; - 176.9; - 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m
, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were similar or lower in subjects who received nintedanib versus placebo across the subgroups. Based on a joint modelling approach, over the whole trial, a 4 kg weight decrease corresponded to a 1.38-fold (95% CI 1.13, 1.68) increase in the risk of acute exacerbation or death. No association was detected between weight loss and the risk of ILD progression or the risk of ILD progression or death.
In patients with PPF, lower BMI at baseline and weight loss may be associated with worse outcomes and measures to prevent weight loss may be required.
https://clinicaltrials.gov/ct2/show/NCT02999178 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inhalation of crystalline silica (SiO
) is a risk factor of systemic autoimmune diseases such as systemic sclerosis (SSc) and fibrotic pulmonary disorders such as silicosis. A defect of apoptotic ...cell clearance (i.e., efferocytosis, a key process in the resolution of inflammation) is reported in macrophages from patients with fibrotic or autoimmune diseases. However, the precise links between SiO
exposure and efferocytosis impairment remain to be determined. Answering to this question may help to better link innate immunity and fibrosis. In this study, we first aim to determine whether SiO
might alter efferocytosis capacities of human and mouse macrophages. We secondly explore possible mechanisms explaining efferocytosis impairment, with a specific focus on macrophage polarization and on the RhoA/ROCK pathway, a key regulator of cytoskeleton remodeling and phagocytosis. Human monocyte-derived macrophages (MDM) and C57BL/6J mice exposed to SiO
and to CFSE-positive apoptotic Jurkat cells were analyzed by flow cytometry to determine their efferocytosis index (EI). The effects of ROCK inhibitors (Y27632 and Fasudil) on EI of SiO
-exposed MDM and MDM from SSc patients were evaluated
. Our results demonstrated that SiO
significantly decreased EI of human MDM
and mouse alveolar macrophages
. In human MDM, this SiO
-associated impairment of efferocytosis, required the expression of the membrane receptor SR-B1 and was associated with a decreased expression of M2 polarization markers (CD206, CD204, and CD163). F-actin staining, RhoA activation and impairment of efferocytosis, all induced by SiO
, were reversed by ROCK inhibitors. Moreover, the EI of MDM from SSc patients was similar to the EI of
- SiO
-exposed MDM and Y27632 significantly increased SSc MDM efferocytosis capacities, suggesting a likewise activation of the RhoA/ROCK pathway in SSc. Altogether, our results demonstrate that SiO
exposure may contribute to the impairment of efferocytosis capacities of mouse and human macrophages but also of MDM in SiO
-associated autoimmune diseases and fibrotic disorders such as SSc; in this context, the silica/RhoA/ROCK pathway may constitute a relevant therapeutic target.
Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been assessed in infections managed by ...repeated therapeutic thoracentesis (RTT).
We performed a retrospective comparative study of two successive cohorts of consecutive patients with pleural infections from 2001 to 2018. Between 2001 and 2010, patients had RTT with intrapleural urokinase (RTT-U). After 2011, patients received intrapleural urokinase and DNase with RTT (RTT-UD). Data were collected through a standardized questionnaire.
One hundred and thirty-three patients were included: 93 were men and the mean age was 59 years (standard deviation 17.2). Eighty-one patients were treated with a combination of intrapleural urokinase and DNase, and 52 were treated with intrapleural urokinase only. In the RTT-UD, RTT failure occurred in 14 patients (17%) compared to 10 (19%) in the RTT-U group (P = 0.82). There was no difference between the two groups in intensive care unit admission, surgical referrals or in-hospital mortality. RTT-UD was associated with faster time to apyrexia (aOR = 0.51, 95%CI 0.37-0.72), a reduced length of hospital stay (aOR = 0.61, 95%CI 0.52-0.73) and a higher volume of total pleural fluid retrieved (aOR = 1.38, 95%CI 1.02-1.88). Complications were rare with only one hemothorax in the RTT-UD group and no pneumothorax requiring drainage in either group.
Compared to urokinase only, intrapleural use of urokinase and DNase in RTT was associated with quicker defervescence, shorter hospital stay and increased volumes of pleural fluid drained. Randomized controlled trials evaluating urokinase and DNase with RTT technique would be required to confirm these results.
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Introduction. About 10% of the 300 million people worldwide who suffer from asthma have a severe disease that is uncontrolled despite treatment with inhaled corticosteroids and long-acting beta ...agonists. The eosinophilic inflammation pathway in the respiratory tract and blood is involved and interleukin-5 (IL-5) has recently been identified as a major promotor of this pathway. The anti-IL-5 antibodies reduce the incidence of exacerbation and allowed steroid sparing in severe asthma patients but only two case reports have been published on their use in critical care. Case Presentation. This report describes the extraordinary clinical improvement of a young patient with steroid-refractory eosinophilic acute severe asthma who required mechanical ventilation, VV-ECMO followed by treatment with mepolizumab. The salient point in this case is the use of an anti-IL-5 monoclonal antibody for a critically ill patient whose condition was deteriorating despite mechanical ventilation and VV-ECMO. The usual steroid treatment failed to control the increase in blood eosinophils or his bronchial inflammation and constriction. Conclusion. Anti-IL-5 antibodies are now a standard treatment for severe eosinophilic asthma that can also be useful in an emergency to treat steroid-refractory eosinophilic acute severe asthma.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce ...intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR‐4/CD14 membrane complex, NF‐kB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger‐associated molecular pattern. This elucidation of the origin and inflammation‐induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.—Lévêque, M., Simonin‐Le Jeune, K., Jouneau, S., Moulis, S., Desrues, B., Belleguic, C., Brinchault, G., Le Trionnaire, S., Gangneux, J.‐P., Dimanche‐Boitrel, M.‐T., Martin‐Chouly, C. Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production. FASEB J. 31, 1891–1902 (2017). www.fasebj.org
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Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to ...search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.
We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.
Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.
There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.
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Objective
Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at ...diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long‐term outcomes.
Methods
A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis.
Results
We identified 383 patients diagnosed between 1957 and June 2009 (128 33.4% before 1997 or earlier) and followed up for a mean ± SD of 66.8 ± 62.5 months. At diagnosis, their mean ± SD age was 50.3 ± 15.7 years, and 91.1% had asthma (duration 9.3 ± 10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA‐positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA‐negative patients. Vasculitis relapses occurred in 35.2% of the ANCA‐positive versus 22.5% of the ANCA‐negative patients (P = 0.01), and 5.6% versus 12.5%, respectively, died (P < 0.05). The 5‐year relapse‐free survival rate was 58.1% (95% confidence interval 95% CI 45.6–68.6) for ANCA‐positive and 67.8% (95% CI 59.8–74.5) for ANCA‐negative patients (P = 0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse.
Conclusion
The characteristics and long‐term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.
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