Preoperative DLCO predicts severe early complications after liver transplantation.

BACKGROUND: Severe early complications are common after liver transplantation (LT) and are a key determinant of LT-related morbidity and mortality. The aim of this study was to assess whether lung function measured in the pre-operative period predicted complicated outcomes in the first month after LT. MATERIAL AND METHODS: Patients with mild-to-moderate liver disease (Model for End stage Liver Disease-MELD score≤30) who underwent LT between October 2015 and May 2020 in a single centre were retrospectively included. The primary endpoint was the occurrence of severe early complications after LT defined by mechanical ventilation duration > 2 days or length of ICU stay > 7 days or reintubation or death < 1 month after LT. RESULTS: One hundred and twenty patients were included (age 59 [53-64] years, 72 % men). Forty patients (33 %) had early complications after LT. Measured and%predicted hemoglobin-corrected lung transfer capacity for carbon monoxide (DLCOc) were significantly lower in patients with severe early complications after LT. DLCOc was the only variable that associated independently with severe early complications by multivariate analysis. DLCOc under 16.3 ml.min-1.mmHg-1 predicted respiratory complications with a sensitivity of 67.5 % and a specificity of 62.9 %. DLCOc%pred under 61.5 % had a sensitivity of 56.8 % and a specificity of 72 %. DLCOc independently associated with forced vital capacity (FVC), pulmonary emphysema, and the muscle mass index. CONCLUSION: A decrease in DLCOc indicated an increased risk of severe early complications after LT.

Smoking, Urban Housing and Work-Aggravated Asthma are Associated with Asthma Severity in a Cross-Sectional Observational Study.

Purpose: Severe asthma affects 5 to 10% of asthmatics and accounts for a large part of asthma-related morbidity and costs. The determinants of asthma severity are poorly understood. We tested the hypothesis that asthma severity was associated with 1) atopy and allergy and 2) markers associated with environmental exposure. Patients and Methods: Data from the FASE-CPHG study, a cross-sectional, observational, multicenter investigation, were analyzed to identify markers associated with asthma severity. Asthma severity was gauged using the ASSESS score, encompassing symptom control, exacerbations, FEV1 and therapeutic load. Bivariate and multivariate analyses were used to identify patient characteristics associated with the ASSESS score. Results: The analysis involved 948 patients, with 592 women, of which 447 patients (47%) had severe asthma. Among these, 491 patients (52%) had at least one positive aeroallergen skin prick test and 525 (55%) had at least one allergic disease among atopic dermatitis, chronic rhinitis and food allergy. The mean±SD ASSESS score was 11.2±3.4. Characteristics associated with a higher ASSESS score were female sex, secondary or lower education, unemployed occupational status, smoking, work-aggravated asthma and urban housing. There was no association between the ASSESS score and allergic diseases, aeroallergen-specific skin prick tests and IgEs, or blood eosinophil counts. Conclusion: While atopy and allergy were frequent among asthmatics, neither was associated with asthma severity. Modifiable environmental factors such as smoking, urban housing and work-aggravated asthma were independently associated with asthma severity.

Association of forced oscillation technique measurements with respiratory system compliance and resistance in a 2-compartment physical model.

BACKGROUND: The forced oscillation technique (FOT) may be useful for diagnosis and follow-up of respiratory diseases. It is unclear how global or regional alterations in airway resistance (Raw) and lung compliance (CL) alter FOT measurements. METHODS: A 2-compartment physical model of the respiratory system allowed to simulate variations in Raw, CL, and their heterogeneity during tidal breathing in an adult human. Five-Hz respiratory system resistance (Rrs5) and reactance (Xrs5), area of reactance (AX), resonance frequency (Fresp) and intrabreath variation in Rrs5 and Xrs5 were measured by FOT. Frequency dependance of resistance could not be studied in this model. Relationships between model characteristics (Raw, CL, and heterogeneity) and FOT measurements were explored by multiple regression. RESULTS: Rrs5 and intrabreath variation in Rrs5 and Xrs5 strongly associated with model characteristics (R2=0.753, 0.5 and 0.658). Associations of Xrs5, AX, and Fresp with model characteristics were weak (R2=0.214, 0.349 and 0.076). Raw heterogeneity was the main determinant of Rrs5 (Coeff=0.594), AX (Coeff=0.566) and intrabreath variation in Rrs5 and Xrs5 (Coeff=0.586 and 0.732). Regional extremes in Raw strongly determined Rrs5 (Coeff=1.006). Xrs5 did not strongly associate with any model characteristic. CONCLUSION: Raw heterogeneity and maximal regional Raw were the main determinants of FOT measurements, in particular Rrs5. Associations between CL and FOT measurements were weak.

Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial.

BACKGROUND: Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. METHODS: In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. RESULTS: Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively). CONCLUSIONS: Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial.

BACKGROUND: A written action plan (WAP) for managing asthma exacerbations is recommended. OBJECTIVE: We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. METHODS: This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. RESULTS: Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI -0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. CONCLUSIONS: The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT02869958.

Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy. METHODS: In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6 months and safety. FINDINGS: Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group. INTERPRETATION: Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.

[Real-life survival of idiopathic pulmonary fibrosis with anti-fibrotic medication]. / Survie en vie réelle des patients ayant une fibrose pulmonaire idiopathique sous traitement anti-fibrosant.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an irreversible fibrosing disease with median survival at diagnosis of 2-5 years. That said, pirfenidone and nintedanib slow down the gradual decline in respiratory function. Clinical trials have shown that while they are not curative, these drugs reduce mortality and increase survival time compared to placebo. This objective of this work was to compare the real-life survival of patients with IPF diagnosed at the Tours University Hospital depending on whether or not they took anti-fibrotic medication. METHODS: This is a monocentric retrospective study involving 176 patients diagnosed with IPF starting from 1997. Out of these 176 patients, 100 were treated with anti-fibrotic agents and 76 did not receive any anti-fibrotic treatment. RESULTS: Survival significantly increased in the group with anti-fibrotic medication, with median survival of 59 months [46-87] versus 39 months [29-65] (P=0.022). Predictive factors for death were neoplasia, IPF exacerbation and decreased DLCO. CONCLUSION: Our study corroborates the beneficial result observed in clinical trials by showing longer survival in patients using anti-fibrotic agents.

1-year mortality in lung cancer in France according to key timepoints of care pathways.

Background: It is unclear whether delays in care affect prognosis of patients with lung cancer. The primary objective of this study was to describe the care pathway of patients diagnosed with lung cancer in a French region. Secondary objectives were to identify markers associated with 1) time from imaging to treatment and 2) with 1-year survival. Methods: In a retrospective cohort study, clinical data from multidisciplinary team meetings for all incident lung cancer cases discussed in 2018 in one French region were matched with medico-administrative data from the National Health Insurance Database. Care pathway time intervals were estimated for small cell lung cancer (SCLC), resected nonsmall cell lung cancer (NSCLC) and unresected NSCLC. Factors associated with delay in the care pathway were identified using linear regression; 1-year survival was analysed using Cox modelling. Results: A total of 685 patients were included. Median time between imaging and treatment was 49 days (interquartile range: 33-73), and was lower in cases of metastatic disease, SCLC and private care. At 1 year, 48% had died (resected NSCLC 12%). In unresected NSCLC, time from diagnostic imaging to first treatment <49 days was associated with a higher risk of death. Time intervals were similar in patients with squamous cell carcinoma versus adenocarcinoma or undifferentiated carcinoma. Discussion: Time intervals in the care pathways of lung cancer were similar to previous reports, confirming the robustness of retrospective databases. In unresectable NSCLC, rapid care was not associated with better survival.

The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature.

OBJECTIVE: The gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list.

Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol.

INTRODUCTION: COVID-19 is responsible of severe hypoxaemia and acute respiratory distress syndrome (ARDS). Prone positioning improves oxygenation and survival in sedated mechanically patients with ARDS not related to COVID-19. Awake prone positioning is a simple and safe technique which improves oxygenation in non-intubated COVID-19 patients. We hypothesised that early prone positioning in COVID-19 patients breathing spontaneously in medical wards could decrease the rates of intubation or need for noninvasive ventilation or death. METHODS AND ANALYSIS: PROVID-19 is an investigator-initiated, prospective, multicentre randomised, controlled, superiority trial comparing awake prone positioning to standard of care in hypoxaemic COVID-19 patients in 20 medical wards in France and Monaco. Patients are randomised to receive either awake prone position plus usual care or usual care alone with stratification on centres, body mass index and severity of hypoxaemia.The study objective is to compare the rate of treatment failure defined as a composite endpoint comprising the need for non-invasive ventilation (at two pressure levels) or for intubation or death, between the intervention group (awake prone position plus usual care) and the usual care (usual care alone) group at 28 days. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the ethics committees (Comité de protection des personnes Ouest VI, France, no 1279 HPS2 and Comité Consultatif d'Ethique en matière de Recherche Biomédicale, Monaco, no 2020.8894 AP/jv), and patients are included after written informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04363463.

International consensus on lung function testing during the COVID-19 pandemic and beyond.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

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

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.

Inhibition of the Arp2/3 complex represses human lung myofibroblast differentiation and attenuates bleomycin-induced pulmonary fibrosis.

BACKGROUND AND PURPOSE: The Arp2/3 multiprotein complex regulates branched polymerisation of the actin cytoskeleton and may contribute to collagen synthesis and fibrogenesis in the lung. EXPERIMENTAL APPROACH: Expression of Arp2/3 components was assessed in human lung fibroblasts and in the bleomycin-induced pulmonary fibrosis model in mice. The Arp2/3 complex was repressed with the allosteric inhibitor CK666 and with interfering RNAs targeting the ARP2, ARP3 and ARPC2 subunits (siARP2, siARP3 and siARPC2) in CCD-16Lu human lung fibroblasts in vitro. Mice received daily intraperitoneal injections of CK666 from the 7th to the 14th day after tracheal bleomycin instillation. KEY RESULTS: Expression of Arp2/3 complex subunits mRNAs was increased in fibroblasts treated with TGF-ß1 and in the lungs of bleomycin-treated mice compared with controls. In vitro, CK666 and siARPC2 inhibited cell growth and TGF-ß1-induced α-smooth muscle actin (ACTA2) and collagen-1 (COL1) expression. CK666 also decreased ACTA2 and COL1 expression in unstimulated cells. CK666 reduced Akt phosphorylation and repressed phospho-GSK3ß, ß-catenin and MRTF-A levels in unstimulated fibroblasts. In vivo, CK666 reduced levels of both procollagen-1 and insoluble collagen in bleomycin-treated mice. CONCLUSION AND IMPLICATIONS: Expression of the Arp2/3 complex was increased in profibrotic environments in vitro and in vivo. Inhibition of the Arp2/3 complex repressed ACTA2 and COL1 expression and repressed an Akt/phospho-GSK3ß/ß-catenin/MRTF-A pathway in lung fibroblasts. CK666 exerted antifibrotic properties in the lung in vivo. Inhibition of the Arp2/3 complex could represent an interesting new therapy for idiopathic pulmonary fibrosis and other fibrotic interstitial lung diseases.

Independent Association Between Occupational Exposure and Decline of FVC in Systemic Sclerosis: A Multicenter Recruitment Retrospective Cohort Study.

BACKGROUND: Although male sex is associated with poor prognosis in systemic sclerosis (SSc), it is unclear whether this association is independent of confounding factors such as occupational exposure to toxicants. RESEARCH QUESTION: What is the respective impact of sex and occupational exposure on characteristics of patients with SSc with a focus on lung function decline? STUDY DESIGN AND METHODS: Patients with SSc (n = 210; 55 men) underwent standardized quantitative assessment of occupational exposure through a cumulative exposure score (CES) in a multicenter recruitment retrospective cohort. Association of the CES with patients' characteristics was assessed. Mixed linear, logistic, and Cox regression models were used to identify predictors of time variation of FVC and the diffusing capacity of the lungs for CO2 corrected for hemoglobin (Dlcoc). RESULTS: Male sex was associated strongly with occupational exposure (OR, 10.3; P < .0001). The CES was correlated inversely (r = -0.20) and associated independently with decline in FVC over time and with occurrence of FVC decline of ≥ 10% from baseline (P < .05). By contrast, the CES was not associated with decline in Dlcoc or Dlcoc decline of ≥ 15%. No independent association was found between sex and decline in FVC or Dlcoc. The prevalence of interstitial lung disease was similar across sex or occupational exposure. INTERPRETATION: Occupational exposure to toxicants seems to predict decline of FVC in patients with SSc independently, regardless of sex. Assessment of occupational exposure may be useful for SSc prognostication.

Micro-phenomenological approach to explore the patient experience during an initial spirometry examination to diagnose COPD in general practice in France.

OBJECTIVES: To explore the patient experience of a spirometry test used to confirm chronic obstructive pulmonary disease (COPD) diagnosis in patients with suspected smoking-related COPD. DESIGN: This is a qualitative study, performed with open interviews in adults following a routine spirometry test to confirm COPD diagnosis. Data were analysed with a phenomenological-inspired micro-phenomenology approach. PARTICIPANTS: Eligible patients were recruited through their general practitioner, 10 were interviewed. SETTING: Primary care in Centre-Val-De-Loire area, France, in 2018. RESULTS: Participants reported the spirometry test experience as being unfamiliar but gave meaning to the symptoms they experience. Participants expressed a desire to perform the test well and a willingness to confront their state of health. After the spirometry had been completed and the results announced, participants moved through stages of grief from their pre-spirometry self and symptom perception to a state of acceptance. Overall, participants expressed a narrative of an evolving cognitive and corporeal awareness during this spirometry experience. The verbatim quotes describe a cognitive rupture with their chronic illness usually considered as a 'way of life'. CONCLUSIONS: A spirometry test goes beyond a diagnostic value, providing patients with an opportunity to gain awareness of their own state of health, reframe their breathlessness-related limitations and thus begin to accept the disease. These awareness gains may be considered as small steps towards health behavioural change. Spirometry may have educative potential and support lifestyle changes.

Alteration of Diffusion Capacity After SARS-CoV-2 Infection: A Pathophysiological Approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected millions of people worldwide, and pneumonia affects 90% of patients. This raises the possibility of millions of people with altered lung function. Few data exist to date on pulmonary function after SARS-CoV-2 infection, but alteration of diffusion capacity of CO (D LCO) is the most frequently described abnormality. First, we present original data on lung function at 3 months after SARS-CoV-2 infection and discuss the effect of using European Coal and Steel Community (ECSC) or Global Lung Function Initiative (GLI) reference equations to diagnose diffusion capacity. Second, we review existing data on D LCO alteration after SARS-CoV-2 infection and discuss the implication of restrictive disorder in D LCO alteration. Last, we discuss the pathophysiology of D LCO alteration and try to disentangle vascular damage and fibrosis.

ThOracic Ultrasound in Idiopathic Pulmonary Fibrosis Evolution (TOUPIE): research protocol of a multicentric prospective study.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is the most common and severe interstitial lung disease (ILD). It is a progressive disease that requires a regular follow-up: clinical examination, pulmonary function testing (PFT) and CT scan, which is performed yearly in France. These exams have two major disadvantages: patients with severe dyspnoea have difficulties to perform PFT and repeated CT scans expose to high dose of radiations. Considering these limits, it would be relevant to develop new tools to monitor the progression of IPF lesions. Three main signs have been described in ILD with lung ultrasound (LUS): the number of B lines, the irregularity and the thickening of the pleural line. Cross-sectional studies already correlated the intensity of these signs with the severity of fibrosis lesions on CT scan in patients with IPF, but no prospective study described the evolution of the three main LUS signs, nor the correlation between clinical evaluation, PFT and CT scan. Our hypothesis is that LUS is a relevant tool to highlight the evolution of pulmonary lesions in IPF. The main objective of our study is to show an increase in one or more of the three main LUS signs (total number of B lines, pleural line irregularity score and pleural line thickness) during the follow-up. METHODS: ThOracic Ultrasound in Idiopathic Pulmonary Fibrosis Evolution is a French prospective, multicentric and non-interventional study. Every 3 months, patients with IPF will have a clinical examination, PFT and LUS. CT data will be collected if the CT scan is performed within 3 months before the inclusion; the second CT scan will be performed from 9 to 12 months after the inclusion. The presence, location and severity of LUS signs will be recorded for each patient, and their correlation with clinical, functional and CT scan evolution will be evaluated. 30 patients will be enrolled. ETHICS AND DISSEMINATION: The protocol was approved by the French Research Ethics Committee (Comité de Protection des Personnes SUD OUEST ET OUTRE MER II, reference RIPH3-RNI19-TOUPIE) on 11 April 2019. Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER: NCT03944928;Pre-results.

Transcutaneous PCO2 -based dead space ventilation at submaximal exercise accurately discriminates healthy controls from patients with chronic obstructive pulmonary disease.

BACKGROUND: Increased physiological dead space ventilation (VD /VT ) at exercise reflects pulmonary gas exchange impairment and is a sensitive marker of cardio-respiratory disease. VD /VT is typically not measured during routine cardiopulmonary exercise testing (CPET) because its calculation requires arterial blood gas analysis for determination of PaCO2 . Instead, dead space ventilation is indirectly evaluated as a determinant of the ventilation (VE)/VCO2 relationship, which also depends on the PaCO2 set point. We hypothesized that VD /VT calculations based on non-invasive transcutaneous PCO2 (PtcCO2 ) measurement had better diagnostic characteristics than the VE/VCO2 slope for the discrimination of healthy subjects from patients with COPD, a common disease associated with impaired pulmonary gas exchange. METHODS: Retrospective study of 19 healthy controls and 24 COPD patients who underwent CPET with continuous PtcCO2 monitoring. Areas under receiver operating characteristics curves (AUC) were calculated to assess diagnostic accuracy of CPET measurement for the discrimination of COPD and Controls. RESULTS: The AUC for PtcCO2 -based VD /VT at VT1 (0.977) was significantly higher than for the VE/VCO2 slope (0.660), SpO2 at peak exercise (0.913), decrease in inspiratory capacity (0.719), and ventilatory reserve (0.708). At a threshold of 0.24, the sensitivity and specificity of PtcCO2 -based VD /VT for the discrimination of COPD patients and healthy Controls were 100% and 84%, respectively. All Control subjects had PtcCO2 -based VD /VT  ≤ 0.25. CONCLUSIONS: PtcCO2 -based VD /VT was the most accurate measurement to discriminate healthy controls from subjects with COPD, a chronic lung disease associated with altered pulmonary gas exchange. Non-invasive monitoring of PtcCO2 may be useful for routine CPET.

Impulse oscillometry and spirometry measurements relative to personal best values at the time of acute exacerbations of cystic fibrosis in adults.

BACKGROUND: Diagnosis of acute exacerbation (AE) of cystic fibrosis (CF) must be precise because both under- and over-prescription of antibiotics may be detrimental. How lung function tests contribute to diagnose AE is unclear. We aimed to describe variation of spirometry and oscillometry measurements, at Stable state and at AE in adults with CF. METHODS: Patients were included in a retrospective single-centre study when both spirometry (FEV1, FVC) and oscillometry (X5, R5, R5-R20 and AX) data were available for at least one Stable and one AE visit between December 2016 and July 2019. For each visit, we calculated variation (Δ) in spirometry and oscillometry indices in comparison with personal best values. Measurements were expressed as % of predicted values and Z-scores when applicable. Areas under ROC curves (AUC) were computed. RESULTS: Forty-two patients (28 ± 9 years, FEV1 64 ± 21%) were included; 80 AE and 104 Stable visits were analysed. FEV1 (L, %pred and Z-score) and FVC (%pred and Z-score) varied significantly between AE and Stable visits (p < .05), although differences were small (80 ml/2.7%pred for FEV1). Among oscillometry indices, X5 (kPa.s.L-1 ), R5-R20 (kPa.s.L-1 ) and AX (kPa/L) varied significantly. The AUCs for the variation in spirometry indices ranged from 0.601 (ΔFVC L) to 0.635 (ΔFEV1%pred). They were not significantly different from the AUCs for ΔX5 (0.589), ΔR5-R20 (0.649) and ΔAX (0.598). CONCLUSIONS: Performance of both spirometry and oscillometry to discriminate AE from Stable state was poor. Variation of oscillometry indices (X5, R5-R20, AX) may be helpful when spirometry is unreliable or uncomfortable.

Low-Frequency Intrapulmonary Percussive Ventilation Increases Aerosol Penetration in a 2-Compartment Physical Model of Fibrotic Lung Disease.

In patients with fibrotic pulmonary disease such as idiopathic pulmonary fibrosis (IPF), inhaled aerosols deposit mostly in the less affected region of the lungs, resulting in suboptimal pharmacokinetics of airway-delivered treatments. Refinement of aerosol delivery technique requires new models to simulate the major alterations of lung physiology associated with IPF, i.e., heterogeneously reduced lung compliance and increased airway caliber. A novel physical model of the respiratory system was constructed to simulate aerosol drug delivery in spontaneously breathing (negative pressure ventilation) IPF patients. The model comprises upper (Alberta ideal throat) and lower airway (plastic tubing) models and branches into two compartments (Michigan lung models) which differ in compliance and caliber of conducting airway. The model was able to reproduce the heterogeneous, compliance-dependent reduction in ventilation and aerosol penetration (using NaF as a model aerosol) seen in fibrotic lung regions in IPF. Of note, intrapulmonary percussive ventilation induced a 2-3-fold increase in aerosol penetration in the low-compliance/high airway caliber compartment of the model, demonstrating the responsiveness of the model to therapeutic intervention.