Mucus and ciliated cells of human lung : splitting strategies for particle methods and 3D stokes flows

Lung walls are covered by a film of mucus, whose motility is fundamental for a healthy behavior. Indeed, mucus traps inhaled aerosols (bacteria, dust, ...), and moves from smallest to largest airways, until it reaches esophagus where is it swallowed or expectorated. A lot of biological parameters are responsible for mucus motion [6], such as the vibrations of ciliated cells covering lung walls (cilia height, frequency, ...), mucus/air interaction, water saturation in mucin network, mucus thickness

Numerical and experimental investigation of mucociliary clearance breakdown in cystic fibrosis

The human tracheobronchial tree surface is covered with mucus. A healthy mucus is a heterogeneous material flowing toward the esophagus and a major defense actor against local pathogen proliferation and pollutant deposition. An alteration of mucus or its environment such as in cystic fibrosis dramatically impacts the mucociliary clearance. In the present study, we investigate the mechanical organization and the physics of such mucus in human lungs by means of a joint experimental and numerical work. In particular, we focus on the influence of the shear-thinning mucus mobilized by a ciliated epithelium for mucociliary clearance. The proposed robust numerical method is able to manage variations of more than 5 orders of magnitude in the shear rate and viscosity. It leads to a cartography that allows to discuss major issues on defective mucociliary clearance in cystic fibrosis. Furthermore, the computational rheological analysis based on measurements shows that cystic fibrosis shear-thinning mucus tends to aggregate in regions of lower clearance. Yet, a rarefaction of periciliary fluid has a greater impact than the mucus shear-thinning effects

Allergie aux antibiotiques chez les patients atteints de mucoviscidose (revue de la littérature étude rétrospective au CRCM adulte de Midi-Pyrénées)

La mucoviscidose est la plus fréquente des maladies génétiques létales dans les populations d'origine caucasienne. L'évolution vers l'insuffisance respiratoire chronique terminale est déterminée par la colonisation bactérienne et les infections bronchiques récidivantes, en particulier à Pseudomonas aeruginosa. Les traitements antibiotiques sont souvent initiés précocement dans l'histoire de la maladie ; ils sont régulièrement nécessaires et de fortes posologies doivent être employées afin de répondre aux caractéristiques pharmacodynamiques et pharmacocinétiques propres à la mucoviscidose. L'incidence de l'allergie aux antibiotiques est plus importante dans la population de patients atteints de mucoviscidose que dans la population générale. Elle limite le choix des antibiotiques à utiliser, choix déjà restreint par les résistances bactériennes. Les raisons pour lesquelles les réactions d'hypersensibilité surviennent plus fréquemment en contexte de mucoviscidose sont peu développées dans la littérature. Parmi les 94 patients suivis au Centre de Ressources et de Compétences de la Mucoviscidose adulte du CHU de Toulouse, nous avons étudié rétrospectivement ceux qui ont bénéficié au moins une fois dans leur vie d'un traitement antibiotique intraveineux. Les 54 patients inclus cumulent 1285 cures antibiotiques dont 496 ont été retenues pour l'analyse statistique des facteurs de risque. L'allergie aux antibiotiques dans notre population est fréquente, avec une incidence de 16,7%. Elle est caractérisée par la prédominance des réactions non immédiates, par la négativité fréquente des tests cutanés et par la rareté des réactions croisées. Les bêtalactamines, et en particulier la pipéracilline, sont les antibiotiques les plus souvent impliqués. Le risque de développer une réaction d'hypersensibilité est d'autant plus élevé que le patient a bénéficié tôt dans sa vie d'une antibiothérapie intraveineuse. A l'inverse, la dénutrition pourrait réduire le risque de réaction d'hypersensibilité, probablement par l'état d'immunodépression qui l'accompagne. Des résultats intéressants sont obtenus avec les protocoles d'accoutumance, aussi bien dans la littérature que dans l'expérience du CRCM adulte de la région Midi-Pyrénées.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Modeling Cystic Fibrosis and Mucociliary Clearance

International audienceThis chapter considers the investigation of airway clearance efficiency and dysfunction using rheological measurements, modeling and simulations of mucus flows. The work is mainly dedicated to the respiratory epithelium dysfunction subsequently to the consumption of cilia-inhibiting drugs (e.g. nicotine) or viral and/or bacterial infections, and cystic fibrosis, although many respiratory diseases are associated with an altered mucus transport

Bronchiectasis and inhaled tobramycin: A literature review

Background: Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling. Objective: The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis. Methods: A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included. Results: Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported. Conclusions: In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety

Feasibility of home initiation of an airway clearance device (SIMEOX) by telecare in people with non-cystic fibrosis bronchiectasis: a pilot study

Background Mucociliary clearance is a cornerstone of the management of people with non-cystic fibrosis bronchiectasis (NCFB). SIMEOX, an innovative device, could facilitate autonomous airway clearance, but its use requires specific training. We hypothesised that telecare would be an effective means to train people with NCFB in the handling of device and to monitor and promote device adherence.Objectives (1) To evaluate frequency of use of the SIMEOX for 10 weeks after telecare training. (2) To assess user satisfaction and clinical efficacy of the SIMEOX+telecare.Methods Multicentre, prospective, pilot study in adults with NCFB. A SIMEOX was provided to each participant at inclusion. Physiotherapists performed telecare sessions the first 2 weeks (3–5 sessions) for device training and every 10 days to reinforce motivation and provide technical support.Results 22 individuals were included, 21 analysed (38% male; mean±SD age 53±18 years; Bronchiectasis Severity Index 6.6±3.5). Fourteen participants (66.7%; 95% CI 43.1% to 84.5%) performed ≥3 SIMEOX sessions/week (self-reported adherence, primary outcome). Median (Q1; Q3) number of self-reported sessions/week for the whole group was 3.7 (1.8; 5.7). Adherence including web registration was 80.9%. At week 12, participant satisfaction rating was 9.0 (7.9; 10.0) on a 10-point visual analogue scale; respiratory function did not change but quality of life improved (COPD Assessment Test score −4.7, 95% CI −7.7 to −1.6, p=0.023; St Georges Respiratory Questionnaire −5.8, 95% CI −10.8 to −0.9, p=0.005).Conclusion Adherence to and satisfaction with the SIMEOX airway clearance device supported by telecare were high in people with NCFB. The clinical efficacy needs to be confirmed in a randomised controlled trial.Trial registration number NCT04742270

Bronchiectasis and inhaled tobramycin:A literature review

Background: Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling. Objective: The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis. Methods: A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included. Results: Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported. Conclusions: In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety

Pulmonary acceleration time to optimize the timing of lung transplant in cystic fibrosis

Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=–0.36, P=0.01). Patients in the lowest PAT tertile (<101 ms) had lower FEV1 and worse nocturnal oxygen saturation, and they were more often on the lung transplant waiting list compared to patients in the other tertiles. Kaplan–Meier curves showed a shorter time to lung transplantation in the lowest PAT tertile (P<0.001) but not in patients with sPAP>35 mmHg. By multivariate analysis, FEV1and nocturnal desaturation were the main determinants of reduced PAT. A PAT<101 ms reduction is a promising tool for timing of lung transplantation in CF

Using chest CT scan and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis

International audienceObjectives Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor. Methods Adolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans. Results A total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (−1.40±1.53 points compared with pretherapeutic CT; p<0.001). This finding was related to a significant decrease in mucus plugging (−0.35±0.62 points; p<0.001), bronchial wall thickening (−0.24±0.52 points; p<0.001) and parenchymal consolidations (−0.23±0.51 points; p<0.001). Cluster analysis identified 3 morphological clusters. Patients from cluster C were more likely to experience an increase in percent predicted forced expiratory volume in 1 sec (ppFEV 1 ) ≥5 under lumacaftor–ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01). Conclusion One year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor