Publications by authors named "Vincent Cottin"

424 Publications

Variability in Global Prevalence of Interstitial Lung Disease.

Front Med (Lausanne) 2021 4;8:751181. Epub 2021 Nov 4.

Interstitial Lung Disease Unit Pulmonology Department, Hospital Universitario de La Princesa, Universidad Autonoma de Madrid, Madrid, Spain.

There are limited epidemiologic studies describing the global burden and geographic heterogeneity of interstitial lung disease (ILD) subtypes. We found that among seventeen methodologically heterogenous studies that examined the incidence, prevalence and relative frequencies of ILDs, the incidence of ILD ranged from 1 to 31.5 per 100,000 person-years and prevalence ranged from 6.3 to 71 per 100,000 people. In North America and Europe, idiopathic pulmonary fibrosis and sarcoidosis were the most prevalent ILDs while the relative frequency of hypersensitivity pneumonitis was higher in Asia, particularly in India (10.7-47.3%) and Pakistan (12.6%). The relative frequency of connective tissue disease ILD demonstrated the greatest geographic variability, ranging from 7.5% of cases in Belgium to 33.3% of cases in Canada and 34.8% of cases in Saudi Arabia. These differences may represent true differences based on underlying characteristics of the source populations or methodological differences in disease classification and patient recruitment (registry vs. population-based cohorts). There are three areas where we feel addition work is needed to better understand the global burden of ILD. First, a standard ontology with diagnostic confidence thresholds for comparative epidemiology studies of ILD is needed. Second, more globally representative data should be published in English language journals as current literature has largely focused on Europe and North America with little data from South America, Africa and Asia. Third, the inclusion of community-based cohorts that leverage the strength of large databases can help better estimate population burden of disease. These large, community-based longitudinal cohorts would also allow for tracking of global trends and be a valuable resource for collective study. We believe the ILD research community should organize to define a shared ontology for disease classification and commit to conducting global claims and electronic health record based epidemiologic studies in a standardized fashion. Aggregating and sharing this type of data would provide a unique opportunity for international collaboration as our understanding of ILD continues to grow and evolve. Better understanding the geographic and temporal patterns of disease prevalence and identifying clusters of ILD subtypes will facilitate improved understanding of emerging risk factors and help identify targets for future intervention.
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http://dx.doi.org/10.3389/fmed.2021.751181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599270PMC
November 2021

Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort.

Adv Ther 2021 Nov 10. Epub 2021 Nov 10.

Pediatric Pneumology Department, Paris-Trousseau University Hospital, Paris, France.

Introduction: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.

Methods: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution).

Results: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified.

Conclusions: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF.

Trial Registration: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).
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http://dx.doi.org/10.1007/s12325-021-01961-xDOI Listing
November 2021

External validation of a refined 4-strata risk assessment score from the French pulmonary hypertension Registry.

Eur Respir J 2021 Nov 4. Epub 2021 Nov 4.

Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France

Introduction: Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate, or high-risk. A minority of patients achieve low-risk status with most remaining intermediate-risk. Our aim was to validate a 4-strata risk assessment approach categorising patients as low, intermediate-low, intermediate-high, or high risk, as proposed by the COMPERA Registry investigators.

Methods: We evaluated incident patients from the French PAH Registry and applied a 4-strata risk method at baseline and at first reassessment. We applied refined cut-points for 3 variables: World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide. We used Kaplan-Meier survival analyses and Cox proportional hazards regression to assess survival according to a 3-strata and 4-strata risk approach.

Results: At baseline (n=2879), the 4-strata approach identified 4 distinct risk groups and performed better than a 3-strata method for predicting mortality. The 4-strata model discrimination was higher than the 3-strata method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. Using the 4-strata approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the 3-strata approach. Those who achieved or maintained a low-risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high.

Conclusions: The 4-strata risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the 3-strata approach.
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http://dx.doi.org/10.1183/13993003.02419-2021DOI Listing
November 2021

Follow-up of two cases of suspected interstitial lung disease following severe COVID-19 infection shows persistent changes in imaging and lung function.

Clin Case Rep 2021 Oct 13;9(10):e04918. Epub 2021 Oct 13.

Universidad Espíritu Santo Samborondón Ecuador.

Physicians are observing persisting symptoms and unexpected organ dysfunction after severe COVID-19. In this report, we present the follow-up of two cases of suspected interstitial lung disease following the viral infection. Up to the last month of follow-up, both patients presented with persistent changes in imaging and pulmonary function tests.
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http://dx.doi.org/10.1002/ccr3.4918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511883PMC
October 2021

Management of Acute Exacerbation of Idiopathic Pulmonary Fibrosis in Specialised and Non-specialised ILD Centres Around the World.

Front Med (Lausanne) 2021 27;8:699644. Epub 2021 Sep 27.

Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus C, Denmark.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide. Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions. Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods. Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.
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http://dx.doi.org/10.3389/fmed.2021.699644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502934PMC
September 2021

Nintedanib in idiopathic and secondary pleuroparenchymal fibroelastosis.

Orphanet J Rare Dis 2021 10 9;16(1):419. Epub 2021 Oct 9.

Department of Respiratory Medicine, National Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, 28 avenue Doyen Lepine, 69677, Lyon, France.

Background: Pleuroparenchymal fibroelastosis (PPFE) has a variable disease course with dismal prognosis in the majority of patients with no validated drug therapy. This study is to evaluate the effect of nintedanib in patients with idiopathic and secondary PPFE. Patients admitted to a tertiary care center (2010-2019) were included into this retrospective analysis if they had a multidisciplinary diagnosis of PPFE, had been followed-up for 3 months or more, and had lung function tests and chest CTs available for review. Changes in pulmonary function tests were assessed using non-parametric tests and linear mixed effect model. Lung volumes were measured with lobar segmentation using chest CT.

Results: Out of 21 patients with PPFE, nine had received nintedanib, six had received another treatment and another six patients were monitored without drug therapy. Annual FVC (% of predicted) relative decline was - 13.6 ± 13.4%/year before nintedanib and - 1.6 ± 6.02%/year during nintedanib treatment (p = 0.014), whereas no significant change in FVC% relative decline was found in patients receiving another treatment (- 13.25 ± 34 before vs - 16.61 ± 36.2%/year during treatment; p = 0.343). Using linear mixed effect model, the slope in FVC was - 0.97%/month (95% CI: - 1.42; - 0.52) before treatment and - 0.50%/month (95% CI: - 0.88; 0.13) on nintedanib, with a difference between groups of + 0.47%/month (95% CI: 0.16; 0.78), p = 0.004. The decline in the upper lung volumes measured by CT was - 233 mL/year ± 387 mL/year before nintedanib and - 149 mL/year ± 173 mL/year on nintedanib (p = 0.327). Nintedanib tolerability was unremarkable.

Conclusion: In patients with PPFE, nintedanib treatment might be associated with slower decline in lung function, paving the way for prospective, controlled studies.
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http://dx.doi.org/10.1186/s13023-021-02043-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501734PMC
October 2021

Idiopathic pulmonary fibrosis: Physician and patient perspectives on the pathway to care from symptom recognition to diagnosis and disease burden.

Respirology 2021 Oct 5. Epub 2021 Oct 5.

Development, Medical Affairs, Galapagos NV, Mechelen, Belgium.

Background And Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that requires ongoing care and is associated with considerable socioeconomic burden. We evaluated the IPF care pathway from symptom recognition to treatment. We describe the impact of IPF on healthcare resource use (HCRU), quality of life (QoL) and work impairment, and report differences in patient and physician perspectives using real-world data from France, Germany, Japan and the United States.

Methods: Quantitative, point-in-time data were collected as part of the Adelphi IPF II Disease Specific Programme™. Physician-reported data (patient demographics, medical history, diagnoses, treatment) were matched to patient-reported data (HCRU, QoL, work impairment). HCRU was measured as physician visits and hospitalizations. QoL and work impairment were measured using the EuroQol-5 Dimensions (EQ-5D) and Work Productivity and Activity Impairment questionnaires.

Results: Overall, 244 physicians reported data on 1249 patients, 739 of whom self-reported data. Diagnostic delays of 0.8 (Germany) to 2.0 (Japan) years after symptom onset were reported; treatment initiation was further delayed. In all countries, patients more often reported symptoms in the survey than did their physicians. On average, patients underwent 7-10 clinical tests before diagnosis. Antifibrotic use increased from 57% (2016) to 69% (2019); only 50% of patients with moderate/severe IPF were satisfied with their treatment. The 12-month hospitalization rates were 24% (Japan) to 64% (United States). Patients reported low QoL (mean EQ-5D visual analogue scale: 61.7/100).

Conclusion: Patients with IPF experience considerable diagnostic and treatment delays. More effective therapies and management are needed to reduce the disease burden.
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http://dx.doi.org/10.1111/resp.14154DOI Listing
October 2021

Post hoc Analysis of Clinical Outcomes in Placebo- and Pirfenidone-Treated Patients with IPF Stratified by BMI and Weight Loss.

Respiration 2021 Oct 5:1-13. Epub 2021 Oct 5.

National Reference Coordinating Center for Rare Pulmonary Diseases, Louis Pradel Hospital and Hospices Civils de Lyon, Université Claude Bernard Lyon 1, UMR754, member of OrphaLung, RespiFil, ERN-LUNG, Lyon, France.

Background: Weight loss is frequently reported in patients with idiopathic pulmonary fibrosis (IPF) and may be associated with worse outcomes in these patients.

Objective: The aim of this study was to investigate the relationships between body mass index (BMI) and weight loss, and outcomes over 1 year in patients with IPF.

Methods: Data were included from placebo patients enrolled in ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729), and all patients in INSPIRE (NCT00075998) and RIFF Cohort A (NCT01872689). An additional analysis included data from pirfenidone-treated patients. Outcomes (annualized change in percent predicted forced vital capacity [%FVC], percent predicted carbon monoxide diffusing capacity, 6-min walk distance, St. George's Respiratory Questionnaire total score, hospitalization, mortality, and serious adverse events) were analyzed by baseline BMI (<25 kg/m2, 25 kg/m2-<30 kg/m2, or ≥30 kg/m2) and annualized percent change in body weight (no loss, >0-<5% loss, or ≥5% loss).

Results: Placebo-treated patients with a baseline BMI <25 kg/m2 or annualized weight loss may experience worse outcomes versus those with a baseline BMI ≥25 kg/m2 or no weight loss. The proportion of placebo-treated patients who experienced a relative decline of ≥10% in %FVC or death up to 1 year post-randomization was highest in patients with a baseline BMI <25 kg/m2. Pirfenidone-treated patients with an annualized weight loss ≥5% may also experience worse outcomes versus those with no weight loss.

Conclusions: Patients with a baseline BMI <25 kg/m2 or annualized weight loss of >0-<5% or ≥5% may experience worse outcomes over 1 year versus those with a baseline BMI ≥25 kg/m2 or no weight loss.
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http://dx.doi.org/10.1159/000518855DOI Listing
October 2021

The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis.

J Clin Med 2021 Sep 14;10(18). Epub 2021 Sep 14.

Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, 69677 Lyon, France.

Variable patterns of disease progression are typically observed in patients with idiopathic pulmonary fibrosis (IPF). We sought to determine the prognostic capacity of blood cell count indexes, derived from routine complete blood cell (CBC) count, in a cohort of IPF patients. The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated at baseline in a consecutive series of 82 IPF patients followed for four years. After adjusting for age, gender, body mass index, smoking status, and disease stage, only the AISI was significantly associated with mortality (HR 1.0013, 95% CI 1.0003-1.0023, = 0.015). Patients with AISI <434 and ≥434 had a median survival from the diagnosis of 35.3 ± 15.2 and 26.6 ± 16.3 months ( = 0.015), and a four-year survival rate of 54% and 34%, respectively. The AISI, easily derivable from routine laboratory tests, is independently associated with mortality in patients with IPF. Prospective studies in larger cohorts are required to confirm this association.
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http://dx.doi.org/10.3390/jcm10184134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466198PMC
September 2021

Historical Patterns of Diagnosis, Treatments, and Outcome of Epilepsy Associated With Tuberous Sclerosis Complex: Results From TOSCA Registry.

Front Neurol 2021 8;12:697467. Epub 2021 Sep 8.

Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of London, London, United Kingdom.

Epilepsy is the most common neurological manifestation in individuals with tuberous sclerosis complex (TSC). However, real-world evidence on diagnosis and treatment patterns is limited. Here, we present data from TuberOus Sclerosis registry to increase disease Awareness (TOSCA) on changes in patterns of epilepsy diagnosis, treatments, and outcomes over time, and detailed epilepsy characteristics from the epilepsy substudy. TuberOus Sclerosis registry to increase disease Awareness (TOSCA) was a multicentre, international disease registry, consisting of a main study that collected data on overall diagnostic characteristics and associated clinical features, and six substudies focusing on specific TSC manifestations. The epilepsy substudy investigated detailed epilepsy characteristics and their correlation to genotype and intelligence quotient (IQ). Epilepsy was reported in 85% of participants, more commonly in younger individuals (67.8% in 1970s to 91.8% in last decade), while rate of treatments was similar across ages (>93% for both infantile spasms and focal seizures, except prior to 1960). Vigabatrin (VGB) was the most commonly used antiepileptic drugs (AEDs). Individuals with infantile spasms showed a higher treatment response over time with lower usage of steroids. Individuals with focal seizures reported similar rates of drug resistance (32.5-43.3%). Use of vagus nerve stimulation (VNS), ketogenic diet, and surgery remained low. The epilepsy substudy included 162 individuals from nine countries. At epilepsy onset, most individuals with infantile spasms (73.2%) and focal seizures (74.5%) received monotherapies. Vigabatrin was first-line treatment in 45% of individuals with infantile spasms. Changes in initial AEDs were commonly reported due to inadequate efficacy. TSC1 mutations were associated with less severe epilepsy phenotypes and more individuals with normal IQ. In individuals with TSC diagnosis before seizure onset, electroencephalogram (EEG) was performed prior to seizures in only 12.5 and 25% of subsequent infantile spasms and focal seizures, respectively. Our study confirms the high prevalence of epilepsy in TSC individuals and less severe phenotypes with mutations. Vigabatrin improved the outcome of infantile spasms and should be used as first-line treatment. There is, however, still a need for improving therapies in focal seizures. Electroencephalogram follow-up prior to seizure-onset should be promoted for all infants with TSC in order to facilitate preventive or early treatment.
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http://dx.doi.org/10.3389/fneur.2021.697467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455825PMC
September 2021

Epidemiology, Mortality and Healthcare Resource Utilization Associated With Systemic Sclerosis-Associated Interstitial Lung Disease in France.

Front Med (Lausanne) 2021 30;8:699532. Epub 2021 Aug 30.

Hôpital Louis Pradel, Centre Coordonnateur National de Référence des Maladies Pulmonaires Rares, Hospices Civils de Lyon, UMR754 INRAE and Université Claude Bernard Lyon 1, Member of ERN-LUNG, RespiFil, OrphaLung, Lyon, France.

To investigate the clinical characteristics, epidemiology, survival estimates and healthcare resource utilization and associated costs in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in France. The French national administrative healthcare database, the Système National des Données de Santé (SNDS), includes data on 98.8% of the French population, including data relating to ambulatory care, hospitalizations and death. In our study, claims data from the SNDS were used to identify adult patients with SSc-ILD between 2010 and 2017. We collected data on clinical features, incidence, prevalence, survival estimates, healthcare resource use and costs. In total, 3,333 patients with SSc-ILD were identified, 76% of whom were female. Patients had a mean age [standard deviation (SD)] of 60.6 (14.4) years and a mean (SD) individual study duration of 3.9 (2.7) years. In 2016, the estimated overall incidence and prevalence were 0.69/100,000 individuals and 5.70/100,000 individuals, respectively. The overall survival estimates of patients using Kaplan-Meier estimation were 93, 82, and 55% at 1, 3, and 8 years, respectively. During the study, 98.7% of patients had ≥1 hospitalization and 22.3% of patients were hospitalized in an intensive care unit. The total annual mean healthcare cost per patient with SSc-ILD was €25,753, of which €21,539 was related to hospitalizations. This large, real-world longitudinal study provides important insights into the epidemiology of SSc-ILD in France and shows that the disease is associated with high mortality, healthcare resource utilization and costs. SSc-ILD represents a high burden on both patients and healthcare services. www.ClinicalTrials.gov, identifier: NCT03858842.
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http://dx.doi.org/10.3389/fmed.2021.699532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451591PMC
August 2021

A call for evidence in connective tissue diseases-associated interstitial lung disease.

Joint Bone Spine 2021 Sep 15;89(1):105274. Epub 2021 Sep 15.

National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, IVPC, INRAE, Claude Bernard University Lyon 1, member of ERN-LUNG, 28, avenue Doyen Lepine, 69677 Lyon cedex, France.

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http://dx.doi.org/10.1016/j.jbspin.2021.105274DOI Listing
September 2021

Impact of Gender on the Characteristics of Patients with Idiopathic Pulmonary Fibrosis Included in the RaDiCo-ILD Cohort.

Respiration 2021 Sep 2:1-12. Epub 2021 Sep 2.

Sorbonne Université, Assistance Publique Hôpitaux de Paris, Hôpital Trousseau, Service de Pneumologie Pédiatrique, Centre de Référence des Maladies Respiratoires Rares, Paris, France.

Background: There is growing evidence of gender-specific phenotypic differences among patients with idiopathic pulmonary fibrosis (IPF), which may affect patient outcomes.

Objectives: We present the characteristics of patients with IPF at inclusion in the French Rare Disease Cohort - Interstitial Lung Disease (RaDiCo-ILD) with the aim of characterizing gender-specific phenotypic differences.

Methods: Patients with IPF who were enrolled in the national, multicentre RaDiCo-ILD cohort were included. Demographic characteristics, comorbidities, health-related quality of life (HRQoL) scores, pulmonary function, chest imaging, and IPF treatment were collected at inclusion and described by gender.

Results: The cohort included 724 patients with IPF (54% of RaDiCo-ILD cohort), of whom 82.9% were male. The proportion of male and female patients with a prior history of smoking was 75.0% and 26.8%, respectively. Emphysema was present in 17.0% (95% confidence interval [CI]: 10.0, 24.0) of men and 5.4% (95% CI: 1.2, 9.6) of women. At inclusion, females had poorer HRQoL than males based on St. George's Respiratory Questionnaire scores (48.5 [95% CI: 43.9, 53.0] and 41.5 [39.4, 43.6], respectively). The mean forced vital capacity per cent predicted was 77.7% (95% CI: 76.2, 79.3) and 87.4% (83.4, 91.4) for males and females, respectively. Honeycombing on high-resolution computed tomography (HRCT) was present in 70.8% (95% CI: 61.0, 80.6) of males and 45.8% (95% CI: 35.1, 56.5) of females.

Conclusions: This analysis of patients with IPF at inclusion in the RaDiCo-ILD cohort provides evidence that comorbid emphysema, lung volume reduction, and honeycombing on HRCT are more common characteristics of males than females.
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http://dx.doi.org/10.1159/000518008DOI Listing
September 2021

Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Respir Med 2021 Sep 7. Epub 2021 Sep 7.

APHP, Service de Radiologie, Hôpital Avicenne, Bobigny, Paris, France.

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/m) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m) 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 χ 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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http://dx.doi.org/10.1016/S2213-2600(21)00354-4DOI Listing
September 2021

Nintedanib in progressive interstitial lung diseases: data from the whole INBUILD trial.

Eur Respir J 2021 Sep 2. Epub 2021 Sep 2.

Department of Medicine, National Jewish Health, Denver, CO, USA

The primary analysis of the INBUILD trial showed that in subjects with progressive fibrosing interstitial lung diseases (ILDs), nintedanib slowed the decline in forced vital capacity (FVC) over 52 weeks. We report the effects of nintedanib on ILD progression over the whole trial.Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice, were randomised to receive nintedanib or placebo. Subjects continued on blinded randomised treatment until all subjects had completed the trial. Over the whole trial, mean (sd) exposure to trial medication was 15.6 (7.2) and 16.8 (5.8) months in the nintedanib and placebo groups, respectively.In the nintedanib (n=332) and placebo (n=331) groups, respectively, the proportions of subjects who had ILD progression (absolute decline in FVC ≥10% predicted) or died were 40.4% and 54.7% in the overall population (HR 0.66 [95% CI: 0.53, 0.83]; p=0.0003), and 43.7% and 55.8% among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT) (HR 0.69 [0.53, 0.91]; p=0.009). In the nintedanib and placebo groups, respectively, the proportions who had an acute exacerbation of ILD or died were 13.9% and 19.6% in the overall population (HR 0.67 [95% CI: 0.46, 0.98]; p=0.04), and 15.0% and 22.8% among subjects with a UIP-like fibrotic pattern on HRCT (HR 0.62 [0.39, 0.97]; p=0.03).Based on data from the whole INBUILD trial, nintedanib reduced the risk of events indicating ILD progression.
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http://dx.doi.org/10.1183/13993003.04538-2020DOI Listing
September 2021

Autophagy and Mitophagy-Related Pathways at the Crossroads of Genetic Pathways Involved in Familial Sarcoidosis and Host-Pathogen Interactions Induced by Coronaviruses.

Cells 2021 08 5;10(8). Epub 2021 Aug 5.

Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, Claude Bernard University Lyon I, IBCP, 69007 Lyon, France.

Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes.
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http://dx.doi.org/10.3390/cells10081995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393644PMC
August 2021

Sjögren disease, not Sjögren's.

Authors:
Vincent Cottin

Arthritis Rheumatol 2021 Aug 23. Epub 2021 Aug 23.

National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, IVPC, INRAE, Bernard University Lyon, member of Radico-ILD and ERN-LUNG, Claude, Lyon, France.

In a recent correspondence, Drs Baer and Hammitt [1] suggested that the terminology of "Sjögren's syndrome" be changed to "Sjögren's disease". The main argument in favor of calling it a disease is that this condition is now very well characterized and identified within the group of connective tissue diseases, with autoimmune pathogenesis. In a very insightful article [2], Dr J. G. Scadding commented about semantic problems in medicine, and stated that there were four main classes of characteristics by which diseases could be defined: 1- the clinical description (syndrome); 2- a disorder of structure with recognisable morbid-anatomical change.
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http://dx.doi.org/10.1002/art.41952DOI Listing
August 2021

Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Front Med (Lausanne) 2021 5;8:713698. Epub 2021 Aug 5.

Centre Constitutif de Référence des Maladies Pulmonaires Rares, AP-HP, Service de Pneumologie, Hôpital Avicenne, Bobigny, France.

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. Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a -test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed. 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 = 32 (62.7%) vs. = 39 (21.1%), < 0.001] and to occupational exposure [ = 7 (13.7%) vs. = 63 (34.1%), = 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 = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [ = 40 (78.4%) vs. = 167 (90.3%) = 0.041] and [ = 6 (11.8%) vs. = 48 (25.9%) = 0.029], respectively. During follow-up fewer women were transplanted compared to men [ = 1 (1.96%) vs. = 20 (10.8%) = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28-40) vs. 40 months (CI 95%: 33-72) = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival. 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.
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http://dx.doi.org/10.3389/fmed.2021.713698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374893PMC
August 2021

Tuberous sclerosis complex for the pulmonologist.

Eur Respir Rev 2021 Sep 3;30(161). Epub 2021 Aug 3.

Dept of Respiratory Medicine, National Reference Coordinating Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either the or gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions. LAM is a multisystem disorder characterised by cystic destruction of lung parenchyma, and may occur in either the setting of TSC (TSC-LAM) or sporadically (S-LAM). LAM occurs in 30-40% of adult females with TSC at childbearing age and is considered a nonmalignant metastatic neoplasm of unknown origin. TSC-LAM is generally milder and, unlike S-LAM, may occur in males. It manifests as multiple, bilateral, diffuse and thin-walled cysts with normal intervening lung parenchyma on chest computed tomography. LAM is complicated by spontaneous pneumothoraces in up to 70% of patients, with a high recurrence rate. mTOR inhibitors are the treatment of choice for LAM with moderately impaired lung function or chylous effusion. MMPH, manifesting as multiple solid and ground-glass nodules on high-resolution computed tomography, is usually harmless with no need for treatment.
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http://dx.doi.org/10.1183/16000617.0348-2020DOI Listing
September 2021

Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European multicenter observational study.

Arthritis Rheumatol 2021 Aug 4. Epub 2021 Aug 4.

Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital and University of Turin, Turin, Italy.

Objective: Mepolizumab proved efficacious for eosinophilic granulomatosis with polyangiitis (EGPA, former Churg-Strauss) at the dosage of 300mg/4 weeks in the randomized controlled MIRRA trial. Few successful real-life experiences with the dosage approved for severe eosinophilic asthma (100mg/4 weeks) were recently reported. We retrospectively assessed the effectiveness and safety of mepolizumab 100 and 300mg/4 weeks in a large European EGPA cohort.

Methods: We included all EGPA patients treated with mepolizumab at the recruiting centres in 2015-2020. Treatment response was evaluated from month 3 through 24 (T3-T24) after mepolizumab starting. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score, BVAS=0) and a prednisone dose ≤4mg/day. Respiratory outcomes included asthma and ear-nose-throat (ENT) exacerbations.

Results: We included 203 patients, of whom 191 at stable dosage (158 mepolizumab 100mg/4 weeks, 33 300mg/4 weeks). At T3, 25 patients (12.3%) had a CR. CR rates increased to 30.4% and 35.7% at T12 and T24 and were comparable between mepolizumab 100 and 300mg/4 weeks. Mepolizumab led to a significant reduction in BVAS, prednisone dose, eosinophil counts from T3 through T24, with no significant differences between 100 and 300 mg/4weeks. Eighty-two patients (40.4%) experienced asthma exacerbations [57/158 (36%) on 100mg/4 weeks; 17/33 (52%) on 300mg/4 weeks]. Thirty-one (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events, most being non-serious (38/44).

Conclusion: Mepolizumab both at 100 and 300mg/4 weeks is effective for EGPA. The two dosages should be compared in the setting of a controlled trial.
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http://dx.doi.org/10.1002/art.41943DOI Listing
August 2021

Early diagnosis of fibrotic interstitial lung disease: challenges and opportunities.

Lancet Respir Med 2021 09 28;9(9):1065-1076. Epub 2021 Jul 28.

Department of Respiratory Medicine, National Reference Coordinating Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France; Department of Respiratory Medicine, Université de Lyon, Université Claude Bernard Lyon 1, UMR754, IVPC, Lyon, France.

Many patients with interstitial lung disease (ILD) develop pulmonary fibrosis, which can lead to reduced quality of life and early mortality. Patients with fibrotic ILD often have considerable diagnostic delay, and are exposed to unnecessary and costly diagnostic procedures, and ineffective and potentially harmful treatments. Non-specific and insidious presenting symptoms, along with scarce knowledge of fibrotic ILD among primary care physicians and non-ILD experts, are some of the main causes of diagnostic delay. Here, we outline and discuss the challenges facing both patients and physicians in making an early diagnosis of fibrotic ILD, and explore strategies to facilitate early identification of patients with fibrotic ILD, both in the general population and among individuals at highest risk of developing the disease. Finally, we discuss controversies and key uncertainties in screening programmes for fibrotic ILD. Timely identification and accurate diagnosis of patients with fibrotic ILD poses several substantial clinical challenges, but could potentially improve outcomes through early initiation of appropriate management.
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http://dx.doi.org/10.1016/S2213-2600(21)00017-5DOI Listing
September 2021

The progressive fibrotic phenotype in current clinical practice.

Curr Opin Pulm Med 2021 09;27(5):368-373

National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, INRAE, IVPC, UMR754, Lyon, France.

Purpose Of Review: The progressive fibrotic phenotype (PFP), a term that covers large sub-groups of patients with fibrotic lung diseases that clinically progress despite appropriate usual management, is now an everyday problem for patients and clinicians alike. This review covers recent data that are relevant to major clinical uncertainties.

Recent Findings: The clinical relevance of the PFP is covered by a brief review of data from which this entity was constructed. Estimates of the prevalence of the PFP are cited. The importance of an accurate initial diagnosis is emphasized - with refutation of the belief that diagnosis now matters less because of recent antifibrotic trial data. Pivotal trials are reviewed briefly with emphasis on the range of diseases studied and the efficacy signals. Included in this section are analyses of treatment effects in individual diseases and data that validate the progression criteria that define the PFP.

Summary: Clinicians can now implement the findings from recent antifibrotic trials in non-idiopathic pulmonary fibrosis lung diseases. However, the appropriate application of recent data requires an understanding of the critical importance of initial diagnosis, key measures of disease progression and knowledge of the strengths and weaknesses of trial data. Important clinical uncertainties not informed by current data include the evaluation of the adequacy of traditional management (before antifibrotic therapy is introduced) and agreement on the exact definition of disease progression that should trigger consideration of antifibrotic therapy.
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http://dx.doi.org/10.1097/MCP.0000000000000805DOI Listing
September 2021

Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA).

Orphanet J Rare Dis 2021 07 6;16(1):301. Epub 2021 Jul 6.

Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of London, London, UK.

Background: Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients.

Methods: TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2).

Results: Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%).

Conclusion: Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.
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http://dx.doi.org/10.1186/s13023-021-01917-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259106PMC
July 2021

Severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A prospective French multicenter cohort.

J Heart Lung Transplant 2021 09 11;40(9):1009-1018. Epub 2021 May 11.

Service de pneumologie B, hôpital Bichat, Paris, France, Université Paris 7, Inserm UMR1152. Electronic address:

Background: A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype.

Methods: We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point.

Results: From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO and PaCO on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months.

Conclusions: Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.
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http://dx.doi.org/10.1016/j.healun.2021.04.021DOI Listing
September 2021

Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med 2021 10;204(7):842-854

Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) ( < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients ( = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients ( = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80;  = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.
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http://dx.doi.org/10.1164/rccm.202009-3698OCDOI Listing
October 2021

[Interstitial lung disease].

Rev Prat 2021 04;71(4):447-457

Service de pneumologie, Centre national coordonnateur de référence des maladies pulmonaires rares, service de pneumologie, hôpital Louis-Pradel, Hospices civils de Lyon, université de Lyon, INRAE, Lyon, France.

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April 2021

Patient-reported outcomes and patient-reported outcome measures in interstitial lung disease: where to go from here?

Eur Respir Rev 2021 Jun 25;30(160). Epub 2021 May 25.

Dept of Respiratory Diseases and Allergy, Centre for Rare Lung Diseases, Aarhus University Hospital, Aarhus N, Denmark.

Patient-reported outcome measures (PROMs), tools to assess patient self-report of health status, are now increasingly used in research, care and policymaking. While there are two well-developed disease-specific PROMs for interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF), many unmet and urgent needs remain. In December 2019, 64 international ILD experts convened in Erice, Italy to deliberate on many topics, including PROMs in ILD. This review summarises the history of PROMs in ILD, shortcomings of the existing tools, challenges of development, validation and implementation of their use in clinical trials, and the discussion held during the meeting. Development of disease-specific PROMs for ILD including IPF with robust methodology and validation in concordance with guidance from regulatory authorities have increased user confidence in PROMs. Minimal clinically important difference for bidirectional changes may need to be developed. Cross-cultural validation and linguistic adaptations are necessary in addition to robust psychometric properties for effective PROM use in multinational clinical trials. PROM burden of use should be reduced through appropriate use of digital technologies and computerised adaptive testing. Active patient engagement in all stages from development, testing, choosing and implementation of PROMs can help improve probability of success and further growth.
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http://dx.doi.org/10.1183/16000617.0026-2021DOI Listing
June 2021

Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study).

Respir Res 2021 May 24;22(1):162. Epub 2021 May 24.

Hôpital Louis Pradel, Centre National de Référence des Maladies Pulmonaires Rares, Hospices Civils de Lyon, Lyon, OrphaLung, RespiFil, ERN-LUNG, Claude Bernard University Lyon 1, 28 Avenue du Doyen Lepine, 69677, Lyon Cedex, France.

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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http://dx.doi.org/10.1186/s12931-021-01749-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147348PMC
May 2021

Care Delivery Models and Interstitial Lung Disease: The Role of the Specialized Center.

Clin Chest Med 2021 06;42(2):347-355

Department of Respiratory Medicine, National Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1, INRAE, IVPC, RespiFil, Radico-ILD and ERN-LUNG, F-69008, UMR754, 28 Avenue Doyen Lepine, Lyon Cedex 69677, France. Electronic address:

Comprehensive interstitial lung disease (ILD) care delivery models have several key components including diagnosis, treatment, monitoring, coordination with other health care providers, patient support/advocacy, education, and research. ILD is rapidly evolving, and specialized centers with ILD-specific expertise have emerged as ways to care for complex patients. The role of the specialized center in care delivery is multifaceted and aimed at improving patient care and advancing the field of ILD. Widespread access to specialized centers is a barrier to ILD care delivery worldwide. Creative and innovative strategies that leverage technology are needed to bridge gaps in ILD care.
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http://dx.doi.org/10.1016/j.ccm.2021.03.013DOI Listing
June 2021

Inhaled Treprostinil in Group 3 Pulmonary Hypertension.

N Engl J Med 2021 May;384(19):1869

University of Lyon, Lyon, France

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http://dx.doi.org/10.1056/NEJMc2103465DOI Listing
May 2021
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